Page last updated: 2024-11-12

veliparib

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Cross-References

ID SourceID
PubMed CID11960529
CHEMBL ID506871
CHEBI ID62880
SCHEMBL ID422318
MeSH IDM0511297

Synonyms (73)

Synonym
2-[(r)-2-methylpyrrolidin-2-yl]-1h-benzimidazole-4-carboxamide
HY-10129
(2r)-2-(7-carbamoyl-1h-benzimidazol-2-yl)-2-methylpyrrolidinium
78P ,
a-861695
nsc-737664
abt-695
abt-888
veliparib ,
(r)-2-(2-methylpyrrolidin-2-yl)-1h-benzo[d]imidazole-4-carboxamide
nsc737664
912444-00-9
2-[(2r)-2-methylpyrrolidin-2-yl]-1h-1,3-benzodiazole-4-carboxamide
benzimidazole carboxamide, 3a
bdbm27135
2-((r)-2-methylpyrrolidin-2-yl)-1h-benzimidazole-4-carboxamide
DB07232
2-((2r)-2-methylpyrrolidin-2-yl)-1h-benzimidazole-4-carboxamide
2-[(2r)-2-methylpyrrolidin-2-yl]-1h-benimidazole-4-
CHEMBL506871
chebi:62880 ,
parp-1 inhibitor abt-888
2-[(r)-2-methylpyrrolidin-2-yl]-1h-benzimidazole-4-carboxamide;
A24888
abt 888
EX-7209
veliparib [usan:inn]
1h-benzimidazole-4-carboxamide, 2-((2r)-2-methyl-2-pyrrolidinyl)-
unii-01o4k0631n
01o4k0631n ,
veliparib (jan/usan/inn)
D09692
2-[(2r)-2-methylpyrrolidin-2-yl]-1h-benzimidazole-4-carboxamide
abt-888 (veliparib)
AKOS015951440
NCGC00250404-01
2-[(2r)-2-methyl-2-pyrrolidinyl]-1h-benzimidazole-7-carboxamide
CS-0076
S1004
BRD-K87142802-001-02-7
2-((2r)-2-methyl-2-pyrrolidinyl)-1h-benzimidazole-7-carboxamide
gtpl7417
veliparib [who-dd]
veliparib [jan]
veliparib [usan]
veliparib [inn]
1h-benzimidazole-7-carboxamide, 2-((2r)-2-methyl-2-pyrrolidinyl)-
AKOS017343746
SCHEMBL422318
smr004701290
MLS006010184
(r)-2-(2-methylpyrrolidin-2-yl)-1h-benzo[d]imidazole-7-carboxamide
a 861695
AC-23330
DTXSID90238456
EX-A001
nsc 737664
bdbm209932
abt888 (free base)
J-505211
veliparib (abt-888 hydrochloride)
2-[(2r)-2-methylpyrrolidin-2-yl]-1h-benzimidazole-7-carboxamide
veliparib free base
912444-00-9 (free base)
(r)-2-(2-methylpyrrolidin-2-yl)-1h-benimidazole-4-carboxamide (veliparib)
AS-19397
Q7919041
SB16480
CCG-264771
NCGC00250404-15
2-[(2r)-2-methylpyrrolidin-2-yl]-1h-benimidazole-4-carboxamide
nsc752840
nsc-752840

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Grades 3-5 adverse events irrespective of attribution during cycle 1 included: dehydration (1), diarrhea (1), fatigue (1), febrile neutropenia (1), heart failure (1), leukopenia (6), lymphopenia (1), nausea (2), neutropenia (8), respiratory failure (1), and thrombocytopenia (2)."( A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511).
Aggarwal, C; Belani, CP; Dahlberg, SE; Dowell, J; Gerber, DE; Hann, CL; Khan, SA; Moss, RA; Owonikoko, TK; Ramalingam, SS, 2015
)
0.42
" During dose escalation, grade 2 dose-limiting toxic effects occurred in two patients; no grade 3-4 dose-limiting toxic effects were noted."( Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.
Czito, BG; DeLuca, A; Deming, DA; Dudley, MW; He, L; Holen, KD; Jameson, GS; Komarnitsky, P; Michael, M; Mittapalli, RK; Mulcahy, MF; Munasinghe, W; Ngan, SY; Vaghefi, H; Zalcberg, JR, 2017
)
0.46
" The most frequent adverse events (AEs) were nausea (78."( Safety and pharmacokinetics of veliparib extended-release in patients with advanced solid tumors: a phase I study.
Dunbar, M; Gutierrez, M; Kittaneh, M; Komarnitsky, P; McKee, M; Sachdev, J; Stein, MN; Sullivan, D; Swisher, EM; Tan, AR; Werner, TL; Xiong, H, 2018
)
0.48
" Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9."( Efficacy and safety of first-line veliparib and carboplatin-paclitaxel in patients with HER2- advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial.
Arun, BK; Ayoub, JP; Bach, BA; Bell-McGuinn, KM; Diéras, V; Friedlander, M; Han, HS; Kaufman, B; Kundu, MG; Maag, D; Puhalla, SL; Ratajczak, CK; Wildiers, H, 2021
)
0.62
"The seven RCTs (n = 2188) showed that patients treated with a combination of veliparib and chemotherapy had a significantly higher risk of adverse events, when compared to the control arm."( Efficacy and safety of veliparib plus chemotherapy for the treatment of lung cancer: A systematic review of clinical trials.
Aletaha, R; Daei Sorkhabi, A; Fazlollahi, A; Feizi, H; Kolahi, AA; Mousavi, SE; Nejadghaderi, SA; Safiri, S; Sarkesh, A; Sullman, MJM, 2023
)
0.91
" Additionally, there are evident adverse reactions."( Efficacy and safety of veliparib combined with traditional chemotherapy for treating patients with lung cancer: a comprehensive review and meta-analysis.
Feng, E; Liu, Y; Zhao, G, 2023
)
0.91

Pharmacokinetics

Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration-time curve compared with immediate-release. No pharmacokinetic interaction was observed when velipsarib and temozolomide were administered together.

ExcerptReferenceRelevance
" Collection of peripheral blood mononuclear cells (PBMCs) as a surrogate tissue to monitor PARP inhibitor pharmacodynamic effects has several advantages over tumor biopsy collection, including minimally invasive sample collection and the ability to collect multiple samples for longitudinal assessment of drug effect."( Modeling pharmacodynamic response to the poly(ADP-Ribose) polymerase inhibitor ABT-888 in human peripheral blood mononuclear cells.
Doroshow, JH; Ji, J; Kinders, RJ; Kummar, S; Parchment, RE; Rubinstein, L; Tomaszewski, JE; Zhang, Y, 2011
)
0.37
"Using our previously validated immunoassay for measuring poly(ADP-ribose) (PAR), a product of PARP, in tumor biopsies, we validated a method to quantify PAR levels in PBMCs to monitor the pharmacodynamic effects of the PARP inhibitor ABT-888 in clinical trials."( Modeling pharmacodynamic response to the poly(ADP-Ribose) polymerase inhibitor ABT-888 in human peripheral blood mononuclear cells.
Doroshow, JH; Ji, J; Kinders, RJ; Kummar, S; Parchment, RE; Rubinstein, L; Tomaszewski, JE; Zhang, Y, 2011
)
0.37
" To this end, the PAR immunoassay has been validated for use with PBMCs and incorporated into clinical trials to assess PBMCs as a potential pharmacodynamic surrogate for tumor biopsies in clinical trials of PARP inhibitors."( Modeling pharmacodynamic response to the poly(ADP-Ribose) polymerase inhibitor ABT-888 in human peripheral blood mononuclear cells.
Doroshow, JH; Ji, J; Kinders, RJ; Kummar, S; Parchment, RE; Rubinstein, L; Tomaszewski, JE; Zhang, Y, 2011
)
0.37
" This analysis characterizes the population pharmacokinetics of veliparib, including developing a structural pharmacokinetic model and testing patient demographics and covariates for potential influence on veliparib pharmacokinetics in patients with non-hematologic malignancies."( Population pharmacokinetic modeling of veliparib (ABT-888) in patients with non-hematologic malignancies.
Giranda, VL; Mostafa, NM; Salem, AH, 2014
)
0.4
" Population pharmacokinetic modeling was performed using NONMEM."( Population pharmacokinetic modeling of veliparib (ABT-888) in patients with non-hematologic malignancies.
Giranda, VL; Mostafa, NM; Salem, AH, 2014
)
0.4
" A physiologically based pharmacokinetic model integrated with a mechanistic kidney module was developed to quantitatively predict the individual and combined effects of renal function, CYP2D6 phenotype, and OCT2 activity on veliparib pharmacokinetics."( Complex disease-, gene-, and drug-drug interactions: impacts of renal function, CYP2D6 phenotype, and OCT2 activity on veliparib pharmacokinetics.
Kim, S; Li, J; LoRusso, P; Sha, X; Wiegand, R; Wu, J, 2014
)
0.4
"Circulating tumor cells (CTCs), which are captured from blood with anti-epithelial cell adhesion molecule (EpCAM) antibodies, have established prognostic value in specific epithelial cancers, but less is known about their utility for assessing patient response to molecularly targeted agents via measurement of pharmacodynamic (PD) endpoints."( Promise and limits of the CellSearch platform for evaluating pharmacodynamics in circulating tumor cells.
Balasubramanian, P; Chen, AP; Evrard, YA; Kinders, RJ; Kummar, S; Wang, L, 2016
)
0.43
" This phase I study evaluated the pharmacokinetics and mass balance of veliparib administered alone and in combination with temozolomide, and assessed any potential pharmacokinetic drug-drug interaction between veliparib and temozolomide."( Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies.
Giranda, V; Munasinghe, W; Nuthalapati, S; Xiong, H, 2018
)
0.48
" No pharmacokinetic interaction was observed when veliparib and temozolomide were administered together."( Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies.
Giranda, V; Munasinghe, W; Nuthalapati, S; Xiong, H, 2018
)
0.48
" Single-dose veliparib-ER 200 mg (fasting) led to 58% lower peak concentration and similar area under the concentration-time curve compared with veliparib immediate-release (IR)."( Safety and pharmacokinetics of veliparib extended-release in patients with advanced solid tumors: a phase I study.
Dunbar, M; Gutierrez, M; Kittaneh, M; Komarnitsky, P; McKee, M; Sachdev, J; Stein, MN; Sullivan, D; Swisher, EM; Tan, AR; Werner, TL; Xiong, H, 2018
)
0.48

Compound-Compound Interactions

Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity. This phase 2, randomized, global study evaluated the efficacy and safety of veliparIB in combination with whole-brain radiation therapy (WBRT) in patients with brain metastases from non-small cell lung cancer.

ExcerptReferenceRelevance
" Taken together, these studies indicate a low potential for veliparib to cause clinically significant P-gp or P450-mediated drug-drug interactions (DDIs)."( Disposition and drug-drug interaction potential of veliparib (ABT-888), a novel and potent inhibitor of poly(ADP-ribose) polymerase.
de Morais, SM; Delzer, J; Lao, Y; Li, X; Voorman, R, 2011
)
0.37
"A phase I trial of ABT-888 (veliparib), a PARP inhibitor, in combination with topotecan, a topoisomerase I-targeted agent, was carried out to determine maximum tolerated dose (MTD), safety, pharmacokinetics, and pharmacodynamics of the combination in patients with refractory solid tumors and lymphomas."( Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas.
Ames, M; Bonner, W; Carter, J; Chen, A; Doroshow, JH; Hollingshead, M; Ji, J; Jia, L; Kinders, R; Kummar, S; Melillo, G; Murgo, AJ; Parchment, RE; Pommier, Y; Reid, JM; Rubinstein, L; Speranza, G; Stotler, H; Tomaszewski, JE; Wang, L; Weil, M; Zhang, Y, 2011
)
0.37
"To assess the possible radiosensitizing capabilities of two different poly(ADP-ribose) polymerase (PARP) inhibitors in combination with external beam and I-tositumomab in a non-Hodgkin's lymphoma cell line."( Poly(ADP-ribose) polymerase inhibitors combined with external beam and radioimmunotherapy to treat aggressive lymphoma.
James, E; Schaefer, NG; Wahl, RL, 2011
)
0.37
" Cyclophosphamide was administered once daily in 21-day cycles in combination with veliparib administered once daily for 7, 14, or 21 days."( A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas.
Allen, D; Belani, CP; Beumer, JH; Chen, A; Doroshow, JH; Gandara, DR; Ji, J; Kiesel, B; Kinders, RJ; Kummar, S; Lenz, HJ; Morgan, R; Newman, EM; Parchment, RE; Puhalla, SL; Rubinstein, L; Tomaszewski, JE; Wang, L; Zhang, Y, 2012
)
0.38
" Taken together, these studies 1) identify DNA repair and checkpoint pathways that are important in ovarian cancer cells treated with FdUrd, ABT-888, and F+A, 2) show that disabling HR at the level of ATR, BRCA1, BRCA2, or RAD51, but not Chk1, ATM, PTEN, or FANCD2, sensitizes cells to ABT-888, and 3) demonstrate that even though ABT-888 sensitizes ovarian tumor cells with functional HR to FdUrd, the effects of this drug combination are more profound in tumors with HR defects, even compared with other chemotherapy + ABT-888 combinations, including cisplatin + ABT-888."( Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination.
Huehls, AM; Huntoon, CJ; Karnitz, LM; Wagner, JM, 2012
)
0.38
"This study suggests that ABT-888 has the clinical potential to enhance the current standard treatment for GBM, in combination with conventional chemo-radiotherapy."( Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma.
Barazzuol, L; Burnet, NG; Jena, R; Jeynes, JC; Kirkby, KJ; Kirkby, NF; Meira, LB, 2013
)
0.39
" These results indicate a low potential for drug-drug interaction (DDI) with OAT1/3, OCT2, or MATE1/2K."( Prediction of clinical drug-drug interactions of veliparib (ABT-888) with human renal transporters (OAT1, OAT3, OCT2, MATE1, and MATE2K).
Andracki, ME; Bow, DA; Carr, RA; Chiou, WJ; De Morais, SM; Kikuchi, R; Lao, Y; Voorman, RL, 2013
)
0.39
" Moreover, ferulic acid, when combined with ABT-888, renders breast cancer cells become hypersensitive to ABT-888."( Ferulic acid in combination with PARP inhibitor sensitizes breast cancer cells as chemotherapeutic strategy.
Choi, YE; Park, E, 2015
)
0.42
" This was a phase 1 dose-escalation study evaluating the safety, and secondarily the antitumor activity of veliparib in combination with whole brain radiation therapy (WBRT) in patients with brain metastases, in order to power future trials."( Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study.
Brade, A; Curran, WJ; Dunbar, M; Giranda, V; Holen, K; Kleinberg, L; Leahy, T; Medina, D; Mehta, MP; Mostafa, NM; Qian, J; Robins, HI; Turaka, A; Wang, D; Wang, F; Xiong, H; Zhu, M, 2015
)
0.42
"The study employed the 3+3 dose escalation design to establish the safety and recommended phase 2 dose (RP2D) of V when combined with fixed doses of C (75 mg/m(2) on day 1) and E (100mg/m(2) on days 1-3) in a 21-day cycle."( A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511).
Aggarwal, C; Belani, CP; Dahlberg, SE; Dowell, J; Gerber, DE; Hann, CL; Khan, SA; Moss, RA; Owonikoko, TK; Ramalingam, SS, 2015
)
0.42
" Veliparib at 100mg in combination with standard doses of C and E was established as the RP2D."( A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer: A trial of the ECOG-ACRIN Cancer Research Group (E2511).
Aggarwal, C; Belani, CP; Dahlberg, SE; Dowell, J; Gerber, DE; Hann, CL; Khan, SA; Moss, RA; Owonikoko, TK; Ramalingam, SS, 2015
)
0.42
"To investigate the effect of poly(ADP-ribose)polymerase(PARP)inhibitor ABT888 combined with carbo on apoptosis of human breast cancer cells."( [Effect of poly(ADP-ribose)polymerase inhibitor combined with carbo on apoptosis of human breast cancer cells].
Ma, QC; Tao, QW; Xia, XY; Yang, B, 2015
)
0.42
"Veliparib at 300 mg twice daily combined with cisplatin and vinorelbine is well tolerated with encouraging response rates."( Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer.
Beumer, JH; Chai, X; Gadi, VK; Giranda, V; Gralow, JR; Griffin, M; Guenthoer, J; Kiesel, BF; Korde, L; Kurland, BF; Linden, HM; Porter, P; Rodler, ET; Shepherd, S; Specht, JM; Strychor, S; Swisher, E; Thompson, JA; Yeh, RF, 2016
)
0.43
" This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan."( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors.
Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016
)
0.43
" The MTD was 100 mg/m(2) irinotecan (days 1 and 8) combined with veliparib 40 mg twice daily (days -1-14) on a 21-day cycle."( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors.
Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016
)
0.43
"Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity."( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors.
Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016
)
0.43
" We screened cancer patients' tumors for FA functional defects then aimed to establish the safety/feasibility of administering PARP inhibitors as monotherapy and combined with a DNA-breaking agent."( Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair.
Bekaii-Saab, T; Chen, A; Duan, W; Ji, J; Lustberg, M; Marshall, J; Rose, J; Schaaf, LJ; Shilo, K; Thurmond, J; Timmers, C; Villalona-Calero, MA; Westman, JA; Xiaobai, L; Zhao, W, 2016
)
0.43
" This phase 2, randomized, global study evaluated the efficacy and safety of veliparib in combination with whole-brain radiation therapy (WBRT) in patients with brain metastases from non-small cell lung cancer (NSCLC)."( Veliparib in combination with whole-brain radiation therapy for patients with brain metastases from non-small cell lung cancer: results of a randomized, global, placebo-controlled study.
Ball, D; Belda-Iniesta, C; Chabot, P; Giranda, V; Gorbunova, V; Holen, KD; Hsia, TC; Kio, E; Mehta, M; Papp, K; Qian, J; Qin, Q; Ryu, JS; Suh, JH, 2017
)
0.46
"The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors."( Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.
Joshi, S; Jue, TR; Khasraw, M; Lester, AJ; McDonald, KL; Nixdorf, S; Nozue, K; Rapkins, RW; Schroder, LB; Whittaker, SP, 2017
)
0.46
"5 mg/kg, twice daily for 5 days in a 28-day treatment cycle) in combination with whole brain RT (4 Gy) induced apoptosis (Tunel staining) and decreased cell proliferation (Ki67 staining) in a PDX of MGMT unmethylated GBM."( Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.
Joshi, S; Jue, TR; Khasraw, M; Lester, AJ; McDonald, KL; Nixdorf, S; Nozue, K; Rapkins, RW; Schroder, LB; Whittaker, SP, 2017
)
0.46
" This phase I study evaluated the pharmacokinetics and mass balance of veliparib administered alone and in combination with temozolomide, and assessed any potential pharmacokinetic drug-drug interaction between veliparib and temozolomide."( Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies.
Giranda, V; Munasinghe, W; Nuthalapati, S; Xiong, H, 2018
)
0.48
"This was an open-label, dose-escalation study of veliparib in combination with temozolomide in 42 subjects with nonhematologic malignancies."( Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies.
Giranda, V; Munasinghe, W; Nuthalapati, S; Xiong, H, 2018
)
0.48
" We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy."( Safety and tolerability of veliparib combined with capecitabine plus radiotherapy in patients with locally advanced rectal cancer: a phase 1b study.
Czito, BG; DeLuca, A; Deming, DA; Dudley, MW; He, L; Holen, KD; Jameson, GS; Komarnitsky, P; Michael, M; Mittapalli, RK; Mulcahy, MF; Munasinghe, W; Ngan, SY; Vaghefi, H; Zalcberg, JR, 2017
)
0.46
" This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine."( Phase I study of veliparib in combination with gemcitabine.
Almokadem, S; Appleman, L; Belani, CP; Beumer, JH; Carneiro, BA; Chen, A; Chu, E; Ding, F; Hershberger, PA; Holleran, J; Jiang, Y; Ken Czambel, R; Kiesel, BF; Kontopodis, E; Lin, Y; Petro, D; Puhalla, S; Rachid, M; Schmitz, JC; Stoller, R, 2017
)
0.46
"This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin and etoposide in patients with extensive-stage (ED) small cell lung cancer (SCLC) and other solid tumors."( A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors.
Atrafi, F; Byers, LA; Calles, A; Camidge, DR; Chae, YK; Gabrail, NY; Garralda, E; Groen, HJM; He, L; Hoening, E; Hu, B; Komarnitsky, P; Lolkema, MP; Nuthalapati, S; Sangha, RS; Tian, T; Viteri, S, 2019
)
0.51
"Thirty-nine patients were enrolled to determine the recommended phase II dose of 240 mg veliparib for 14 days combined with carboplatin and etoposide based on long-term tolerability."( A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors.
Atrafi, F; Byers, LA; Calles, A; Camidge, DR; Chae, YK; Gabrail, NY; Garralda, E; Groen, HJM; He, L; Hoening, E; Hu, B; Komarnitsky, P; Lolkema, MP; Nuthalapati, S; Sangha, RS; Tian, T; Viteri, S, 2019
)
0.51
" Further clinical investigations aimed at elucidating the veliparib exposure-efficacy/safety relationship and optimizing dosing recommendations for maximizing benefit-risk in patients with advanced myeloid malignancies should study veliparib doses ranging up to 120 mg in combination with temozolomide."( Population pharmacokinetics and exposure-response assessment of veliparib co-administered with temozolomide in patients with myeloid leukemias.
Beumer, JH; Chen, A; Gobburu, J; Gojo, I; Gopalakrishnan, M; Greer, JM; Karp, JE; Kiesel, BF; Mehrotra, S; Piekarz, R; Rudek, MA; Singh, R, 2019
)
0.51
" This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC."( A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.
Aghajanian, C; Armstrong, DK; Bell-McGuinn, KM; Chen, A; Duska, LR; Fracasso, PM; Gordon, S; Gray, HJ; Guntupalli, SR; Hagemann, AR; Mathews, CA; Miller, A; Moore, KN; O'Cearbhaill, RE; O'Malley, D; Schilder, RJ; Walker, JL, 2020
)
0.56
" Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020
)
0.56
" This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020
)
0.56
" This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546)."( Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.
Ansell, P; Bach, BA; Bar, J; Bentsion, D; Bernabe, R; Byers, LA; Clingan, P; Dunbar, M; Glasgow, J; Govindan, R; Guclu, SZ; He, L; Huang, X; Mazieres, J; Novello, S; Ramalingam, SS; Sehgal, V; Syrigos, K; Szilasi, M; Vokes, EE; Zvirbule, Z, 2021
)
0.62
"In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status."( Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.
Aghajanian, C; Ansell, PJ; Birrer, MJ; Bookman, MA; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Kaufmann, SH; Levine, DA; Moore, KN; O'Malley, DM; Okamoto, A; Reid, TJ; Sehgal, V; Shahin, MS; Spirtos, NM; Steffensen, KD; Swisher, EM, 2022
)
0.72
"BRCA-Mutated Advanced Breast Cancer (BROCADE3) is a phase 3 study, evaluating veliparib in combination with carboplatin/paclitaxel with continuation as monotherapy if carboplatin/paclitaxel is discontinued in patients with germline BRCA1/2 mutation-associated, advanced human epidermal growth factor receptor 2-negative breast cancer."( Exposure-Response Model With Time-Varying Predictors to Estimate the Effects of Veliparib in Combination With Carboplatin/Paclitaxel and as Monotherapy: Veliparib Phase 3 Study in BRCA-Mutated Advanced Breast Cancer (BROCADE3) Trial.
Eckert, D; Joshi, R; Menon, R; Mensing, S; Nuthalapati, S; Ratajczak, CK; Stodtmann, S; Xiong, H, 2022
)
0.72
" This study aimed to assess the efficacy and safety of Veliparib combined with chemotherapy versus pharmacotherapy alone for lung cancer treatment, guiding clinical approaches for this severe disease."( Efficacy and safety of veliparib combined with traditional chemotherapy for treating patients with lung cancer: a comprehensive review and meta-analysis.
Feng, E; Liu, Y; Zhao, G, 2023
)
0.91
"Comprehensive searches in PubMed, EMBASE, Cochrane, and Web of Science were conducted to identify randomized controlled trials (RCTs) comparing Veliparib combined with standard chemotherapy to chemotherapy alone in lung cancer treatment, up until December 28, 2022."( Efficacy and safety of veliparib combined with traditional chemotherapy for treating patients with lung cancer: a comprehensive review and meta-analysis.
Feng, E; Liu, Y; Zhao, G, 2023
)
0.91

Bioavailability

Veliparib is a Biopharmaceutical Classification System (BCS) Class 1 compound, with no less than 90% of the dose absorbed and an oral bioavailability of at least 73%. A phase 1 study was conducted to evaluate the bioavailability and food effect of a new velipsarib formulation in subjects with solid tumors.

ExcerptReferenceRelevance
"To evaluate the preclinical pharmacokinetics and antitumor efficacy of a novel orally bioavailable poly(ADP-ribose) polymerase (PARP) inhibitor, ABT-888."( ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models.
Bauch, JL; Bontcheva-Diaz, VD; Bouska, JJ; Cox, BF; DeWeese, TL; Dillehay, LE; Donawho, CK; Ferguson, DC; Frost, DJ; Ghoreishi-Haack, NS; Giranda, VL; Grimm, DR; Guan, R; Han, EK; Holley-Shanks, RR; Hristov, B; Idler, KB; Jarvis, K; Johnson, EF; Kleinberg, LR; Klinghofer, V; Lasko, LM; Liu, X; Luo, Y; Marsh, KC; McGonigal, TP; Meulbroek, JA; Olson, AM; Palma, JP; Penning, TD; Rodriguez, LE; Rosenberg, SH; Shi, Y; Stavropoulos, JA; Tsurutani, AC; Zhu, GD, 2007
)
0.34
" The compound has good oral bioavailability and crosses the blood-brain barrier."( ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models.
Bauch, JL; Bontcheva-Diaz, VD; Bouska, JJ; Cox, BF; DeWeese, TL; Dillehay, LE; Donawho, CK; Ferguson, DC; Frost, DJ; Ghoreishi-Haack, NS; Giranda, VL; Grimm, DR; Guan, R; Han, EK; Holley-Shanks, RR; Hristov, B; Idler, KB; Jarvis, K; Johnson, EF; Kleinberg, LR; Klinghofer, V; Lasko, LM; Liu, X; Luo, Y; Marsh, KC; McGonigal, TP; Meulbroek, JA; Olson, AM; Palma, JP; Penning, TD; Rodriguez, LE; Rosenberg, SH; Shi, Y; Stavropoulos, JA; Tsurutani, AC; Zhu, GD, 2007
)
0.34
"ABT-888 is a potent, orally bioavailable PARP-1/2 inhibitor shown to potentiate DNA damaging agents."( The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo.
Bontcheva-Diaz, VD; Bouska, JJ; Bukofzer, G; Colon-Lopez, M; Donawho, CK; Frost, DJ; Giranda, VL; Guan, R; Jarvis, K; Johnson, EF; Klinghofer, V; Liu, X; Luo, Y; Olson, A; Palma, JP; Penning, TD; Rodriguez, LE; Rosenberg, SH; Saltarelli, MJ; Shi, Y; Stavropoulos, JA; Zhu, GD,
)
0.13
" In addition, 3a is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide (TMZ) and in an MX-1 breast cancer xenograft model in combination with either carboplatin or cyclophosphamide."( Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
Bontcheva-Diaz, V; Bouska, JJ; Donawho, CK; Frost, DJ; Gandhi, VB; Giranda, VL; Gong, J; Johnson, EF; Klinghofer, V; Liu, X; Luo, Y; Marsh, KC; Olson, AM; Osterling, DJ; Penning, TD; Shi, Y; Zhu, GD, 2009
)
0.35
" ABT-888 demonstrated good oral bioavailability and was well tolerated."( Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies.
Chen, A; Collins, J; Doroshow, JH; Eliopoulos, H; Giranda, VL; Gordon, G; Gutierrez, ME; Helman, L; Ji, J; Kinders, R; Kummar, S; Low, JA; Monks, A; Murgo, AJ; Parchment, RE; Phillips, LR; Rubinstein, L; Steinberg, SM; Tomaszewski, JE; Wiltrout, R, 2009
)
0.35
"A phase 1 study was conducted to evaluate the bioavailability and food effect of a new veliparib formulation in subjects with solid tumors."( A phase 1 study to evaluate effect of food on veliparib pharmacokinetics and relative bioavailability in subjects with solid tumors.
Bessudo, A; Chiu, YL; Giranda, VL; Kovacs, X; Mostafa, NM; Rosen, LS, 2014
)
0.4
" At the end of Stage I, the relative bioavailability between each pair of regimens was assessed by a two one-sided tests procedure from the analyses of the natural logarithms of C(max) and AUC."( A phase 1 study to evaluate effect of food on veliparib pharmacokinetics and relative bioavailability in subjects with solid tumors.
Bessudo, A; Chiu, YL; Giranda, VL; Kovacs, X; Mostafa, NM; Rosen, LS, 2014
)
0.4
"Veliparib is a potent, orally bioavailable PARP inhibitor that enhances efficacy of DNA-damaging chemotherapeutic agents."( A phase 1 study evaluating the pharmacokinetics and preliminary efficacy of veliparib (ABT-888) in combination with carboplatin/paclitaxel in Japanese subjects with non-small cell lung cancer (NSCLC).
Fujiwara, Y; Giranda, V; Hashiba, H; Horinouchi, H; Kanda, S; Kitazono, S; Mizugaki, H; Nokihara, H; Qian, J; Shepherd, SP; Tamura, T; Xiong, H; Yagishita, S; Yamamoto, N, 2015
)
0.42
" This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan."( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors.
Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016
)
0.43
"Veliparib (ABT-888) is an orally bioavailable potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1 and PARP-2."( Effect of veliparib (ABT-888) on cardiac repolarization in patients with advanced solid tumors: a randomized, placebo-controlled crossover study.
Bergau, D; Calvo, E; de Vos-Geelen, J; Gordon, M; Hoffman, D; Jalving, M; Medina, D; Munasinghe, W; Nuthalapati, S; Shepherd, S; Stodtmann, S; Tolcher, A; Xiong, H, 2016
)
0.43
"The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors."( Veliparib in combination with radiotherapy for the treatment of MGMT unmethylated glioblastoma.
Joshi, S; Jue, TR; Khasraw, M; Lester, AJ; McDonald, KL; Nixdorf, S; Nozue, K; Rapkins, RW; Schroder, LB; Whittaker, SP, 2017
)
0.46
"Veliparib is a Biopharmaceutical Classification System (BCS) Class 1 compound, with no less than 90% of the dose absorbed and an oral bioavailability of at least 73%."( Clinical Pharmacokinetics and Mass Balance of Veliparib in Combination with Temozolomide in Subjects with Nonhematologic Malignancies.
Giranda, V; Munasinghe, W; Nuthalapati, S; Xiong, H, 2018
)
0.48
"Veliparib (ABT-888) is a potent, orally bioavailable poly(ADP-ribose) polymerase-1 and -2 inhibitor."( Phase 1 dose-escalation study of single-agent veliparib in Japanese patients with advanced solid tumors.
Fujiwara, K; Hashiba, H; Imai, Y; Kiriyama, T; Komarnitsky, P; Leahy, T; Matsumoto, K; Miyasaka, A; Nishikawa, T; Nuthalapati, S; Onoe, T; Shimizu, C; Shimoi, T; Tamura, K; Xiong, H; Yamaguchi, S; Yonemori, K; Yoshida, H; Yunokawa, M, 2017
)
0.46
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

In vitro cytotoxicity assays do not adequately model the therapeutic index of PARP inhibitors. In comparing DNA damage signaling after dosing with veliparib/TMZ or TMZ alone, increased phosphorylation of damage-responsive proteins was observed only in MGMT promoter-hypermethylated lines.

ExcerptRelevanceReference
" Extended ABT-888 dosing schedules showed no advantage compared to simultaneous TMZ administration."( The PARP inhibitor, ABT-888 potentiates temozolomide: correlation with drug levels and reduction in PARP activity in vivo.
Bontcheva-Diaz, VD; Bouska, JJ; Bukofzer, G; Colon-Lopez, M; Donawho, CK; Frost, DJ; Giranda, VL; Guan, R; Jarvis, K; Johnson, EF; Klinghofer, V; Liu, X; Luo, Y; Olson, A; Palma, JP; Penning, TD; Rodriguez, LE; Rosenberg, SH; Saltarelli, MJ; Shi, Y; Stavropoulos, JA; Zhu, GD,
)
0.13
" Dosed radioactivity was widely distributed in rat tissues."( Disposition and drug-drug interaction potential of veliparib (ABT-888), a novel and potent inhibitor of poly(ADP-ribose) polymerase.
de Morais, SM; Delzer, J; Lao, Y; Li, X; Voorman, R, 2011
)
0.37
" PARP inhibitors were dosed for 2 days, and then co-administered with vincristine for 12 days."( PARP inhibitors attenuate chemotherapy-induced painful neuropathy.
Brederson, JD; Browman, KE; Gauvin, D; Giranda, VL; Joshi, SK; Liu, X; Mikusa, J; Penning, TD; Shi, Y; Shoemaker, AR; Zhong, C, 2012
)
0.38
" Dosage adjustments of veliparib on the basis of body size, age, sex, race, liver function, and temozolomide coadministration are not necessary in patients with non-hematologic malignancies."( Population pharmacokinetic modeling of veliparib (ABT-888) in patients with non-hematologic malignancies.
Giranda, VL; Mostafa, NM; Salem, AH, 2014
)
0.4
" For intermittent dosing studies, mice cycled through olaparib (200 mg/kg diet) for 2 weeks followed by a 4-week rest period on control diet."( The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice.
Collins, RM; Kim, EH; Liby, KT; Risingsong, R; Royce, DB; Sporn, MB; To, C; Williams, CR, 2014
)
0.4
" In vivo drug efficacy, pharmacokinetics, and pharmacodynamics were analyzed using clinically relevant dosing regimens."( Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multiforme xenografts.
Bakken, KK; Boakye-Agyeman, F; Carlson, BL; Gupta, SK; Kizilbash, SH; Mladek, AC; Reid, J; Sarkaria, JN; Schroeder, MA, 2014
)
0.4
"In vitro cytotoxicity assays do not adequately model the therapeutic index of PARP inhibitors, as concentrations of veliparib and TMZ required to sensitize TMZ-resistant cancer cells in vivo cannot be achieved using a tolerable dosing regimen."( Discordant in vitro and in vivo chemopotentiating effects of the PARP inhibitor veliparib in temozolomide-sensitive versus -resistant glioblastoma multiforme xenografts.
Bakken, KK; Boakye-Agyeman, F; Carlson, BL; Gupta, SK; Kizilbash, SH; Mladek, AC; Reid, J; Sarkaria, JN; Schroeder, MA, 2014
)
0.4
" In comparing DNA damage signaling after dosing with veliparib/TMZ or TMZ alone, increased phosphorylation of damage-responsive proteins (KAP1, Chk1, Chk2, and H2AX) was observed only in MGMT promoter-hypermethylated lines."( Delineation of MGMT Hypermethylation as a Biomarker for Veliparib-Mediated Temozolomide-Sensitizing Therapy of Glioblastoma.
Bakken, KK; Ballman, KV; Boakye-Agyeman, F; Carlson, BL; Cen, L; Decker, PA; Eckel-Passow, JE; Gupta, SK; Jenkins, RB; Kitange, GJ; Kizilbash, SH; Mladek, AC; Pokorny, JL; Reid, JM; Sarkar, G; Sarkaria, JN; Schroeder, MA; Sulman, EP; Verhaak, RG, 2016
)
0.43
" for both dosing arms), myelosuppression was the DLT."( A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study.
Armstrong, DK; Brady, WE; DiSilvestro, PA; Fracasso, PM; Landrum, LM; Moore, KN; O'Malley, DM; Rose, PG; Tenney, ME, 2016
)
0.43
" Twice-daily oral dosing of veliparib (10-50 mg) occurred on days 3 to 14 (cycle 1) and days -1 to 14 (subsequent cycles) followed by a 6-day rest."( Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP-ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors.
Bell, T; Boerner, JL; Boerner, SA; Bowditch, A; Burger, A; Cai, D; Chen, AP; Cleary, JM; Ferry-Galow, K; Heilbrun, LK; Ji, J; Kinders, RJ; Li, J; LoRusso, PM; Marrero, AM; Parchment, RE; Pilat, MJ; Rubinstein, L; Sausville, EA; Shapiro, GI; Smith, D; Tolaney, SM; Wolanski, A; Zhang, J; Zhang, Y, 2016
)
0.43
" This study provides strong scientific rationale for the development of an optimized dosing regimen for a PARP inhibitor with TMZ/IR for upfront treatment of GBM."( Evaluation of Concurrent Radiation, Temozolomide and ABT-888 Treatment Followed by Maintenance Therapy with Temozolomide and ABT-888 in a Genetically Engineered Glioblastoma Mouse Model.
Chenevert, TL; Galbán, CJ; Galbán, S; Heist, KA; Holland, EC; Lemasson, B; Li, Y; Rehemtulla, A; Ross, BD; Tsein, C; Wang, H; Zhu, Y, 2016
)
0.43
" Poly-ADP-ribose-polymerase inhibition sensitizes tumor cells to cytotoxic agents, which induce DNA damage, including cyclophosphamide (C), and metronomic dosing of C may optimize potential for synergy."( Phase I Trial of Veliparib, a Poly ADP Ribose Polymerase Inhibitor, Plus Metronomic Cyclophosphamide in Metastatic HER2-negative Breast Cancer.
Anampa, J; Andreopoulou, E; Chen, A; Fehn, K; Patel, M; Pellegrino, C; Sparano, JA; Wright, J, 2018
)
0.48
"The combination of oral continuous dosing of V (200 mg orally BID) with metronomic C (50, 75, 100, and 125 mg daily) is well-tolerated and shows antitumor activity in patients with BRCA-mutation-associated metastatic human epidermal growth factor receptor 2/neu-negative breast cancer."( Phase I Trial of Veliparib, a Poly ADP Ribose Polymerase Inhibitor, Plus Metronomic Cyclophosphamide in Metastatic HER2-negative Breast Cancer.
Anampa, J; Andreopoulou, E; Chen, A; Fehn, K; Patel, M; Pellegrino, C; Sparano, JA; Wright, J, 2018
)
0.48
" Veliparib was dosed at a volume of 300 mg twice-daily (N = 3), then 400 mg twice-daily (N = 15) days 1-28."( Phase II trial of veliparib in patients with previously treated BRCA-mutated pancreas ductal adenocarcinoma.
Capanu, M; Chen, AP; Do, RKG; Golan, T; Hollywood, E; Kelsen, DP; Kindler, HL; Lee, JW; Lowery, MA; Maynard, H; Moore, MJ; Moynahan, M; O'Reilly, EM; Salo-Mullen, EE; Segal, A; Smith, SC; Stadler, ZK; Tang, LH; Yu, KH, 2018
)
0.48
" Further clinical investigations aimed at elucidating the veliparib exposure-efficacy/safety relationship and optimizing dosing recommendations for maximizing benefit-risk in patients with advanced myeloid malignancies should study veliparib doses ranging up to 120 mg in combination with temozolomide."( Population pharmacokinetics and exposure-response assessment of veliparib co-administered with temozolomide in patients with myeloid leukemias.
Beumer, JH; Chen, A; Gobburu, J; Gojo, I; Gopalakrishnan, M; Greer, JM; Karp, JE; Kiesel, BF; Mehrotra, S; Piekarz, R; Rudek, MA; Singh, R, 2019
)
0.51
"The exposure-response analysis suggested that intermittent 7-day veliparib 120 mg BID dosing in a 21-day cycle provided additional efficacy without meaningfully impacting the safety and tolerability when co-administered with carboplatin and paclitaxel in patients with BRCA-deficient breast cancer."( Exposure-response analysis to inform the optimal dose of veliparib in combination with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer patients.
Menon, R; Mensing, S; Nuthalapati, S; Ratajczak, CK; Shepherd, SP; Stodtmann, S; Xiong, H, 2019
)
0.51
" There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed."( A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.
Aghajanian, C; Armstrong, DK; Bell-McGuinn, KM; Chen, A; Duska, LR; Fracasso, PM; Gordon, S; Gray, HJ; Guntupalli, SR; Hagemann, AR; Mathews, CA; Miller, A; Moore, KN; O'Cearbhaill, RE; O'Malley, D; Schilder, RJ; Walker, JL, 2020
)
0.56
" Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020
)
0.56
"The combination of continuous dosing of veliparib and every-3-week carboplatin demonstrated activity and an acceptable toxicity profile."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020
)
0.56
" Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status."( Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.
Aghajanian, C; Bookman, MA; Chan, JK; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Hashiba, H; Moore, KN; O'Malley, DM; Okamoto, A; Ratajczak, C; Steffensen, KD; Swisher, EM; Tewari, KS; Wu, M, 2022
)
0.72
" PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status."( Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.
Aghajanian, C; Bookman, MA; Chan, JK; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Hashiba, H; Moore, KN; O'Malley, DM; Okamoto, A; Ratajczak, C; Steffensen, KD; Swisher, EM; Tewari, KS; Wu, M, 2022
)
0.72
"Patients (n = 98) were dosed with veliparib 50-500 mg twice daily (BID)."( A phase 1 and pharmacodynamic study of chronically-dosed, single-agent veliparib (ABT-888) in patients with BRCA1- or BRCA2-mutated cancer or platinum-refractory ovarian or triple-negative breast cancer.
Appleman, L; Belani, CP; Beumer, JH; Chen, A; Chew, H; Chu, E; Diergaarde, B; Ding, F; Duan, W; Garcia, AA; Giranda, V; Hurley, RM; Ivy, SP; Ji, J; Katz, T; Kaufmann, SH; Kiesel, BF; Lee, JJ; Lin, Y; Manzo, J; Morgan, RJ; Oesterreich, S; Pahuja, S; Parchment, RE; Puhalla, S; Shepherd, SP; Stoller, R; Swisher, EM; Tan, AR; Tawbi, H; Visscher, DW; Wahner Hendrickson, AE; Yu, J; Zhang, Y, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (1)

RoleDescription
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitorAn EC 2.4.2.* (pentosyltransferase) inhibitor that interferes with the action of a NAD(+) ADP-ribosyltransferase (EC 2.4.2.30).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
benzimidazolesAn organic heterocyclic compound containing a benzene ring fused to an imidazole ring.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (11)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
EWS/FLI fusion proteinHomo sapiens (human)Potency22.50270.001310.157742.8575AID1259252; AID1259256
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Poly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)IC50 (µMol)32.86380.00190.62935.0000AID1064834; AID1428391; AID1895769
Poly [ADP-ribose] polymerase 1Homo sapiens (human)IC50 (µMol)5.60740.00020.81239.8100AID1064455; AID1064607; AID1155630; AID1234864; AID1276413; AID1403931; AID1428384; AID1428385; AID1428386; AID1474432; AID1474435; AID1508852; AID1508889; AID1631788; AID1631792; AID1632628; AID1802336; AID1895766; AID739045; AID762672
Poly [ADP-ribose] polymerase 1Homo sapiens (human)Ki0.00460.00060.65955.0000AID1798781; AID1872299; AID412651; AID441940
Protein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)IC50 (µMol)89.06251.73785.66258.9125AID1428397
Protein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)IC50 (µMol)22.81430.56234.10539.7724AID1428394; AID1428395
Protein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)IC50 (µMol)59.14220.07902.43076.6500AID1428396
Poly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)IC50 (µMol)23.99420.00210.67505.1300AID1428393
Poly [ADP-ribose] polymerase 2Homo sapiens (human)IC50 (µMol)0.06880.00010.21886.6000AID1403932; AID1428387; AID1428388; AID1508854; AID1508890; AID1632629; AID1895767
Poly [ADP-ribose] polymerase 2Homo sapiens (human)Ki0.01120.00070.00480.0175AID1872300; AID412652
Protein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)IC50 (µMol)3.48370.33001.68274.3900AID1428390
Protein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)IC50 (µMol)2.08900.00351.12186.3000AID1428389
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Poly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)Kd10.00000.00800.05370.1000AID1895781
Poly [ADP-ribose] polymerase 1Homo sapiens (human)EC50 (µMol)27.23500.00040.18093.0000AID1276416; AID1683865; AID412653; AID441941; AID762670; AID762671
Poly [ADP-ribose] polymerase 1Homo sapiens (human)Kd0.00230.00020.43565.3100AID1240632; AID1895777
Protein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)Kd6.80003.10006.06009.7000AID1895786
Protein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)Kd10.00001.00001.95002.9000AID1895790
Poly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)Kd10.00000.00421.50918.9000AID1895782
Poly [ADP-ribose] polymerase 2Homo sapiens (human)EC50 (µMol)0.00590.00250.00840.0240AID1276416
Poly [ADP-ribose] polymerase 2Homo sapiens (human)Kd0.00840.00030.29141.4000AID1240634; AID1895778
Protein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)Kd0.10500.00070.20430.5030AID1895780
Protein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)EC50 (µMol)0.00590.00250.00840.0240AID1276416
Protein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)Kd0.23100.00580.24560.7000AID1895779
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (104)

Processvia Protein(s)Taxonomy
peptidyl-serine phosphorylationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
peptidyl-threonine phosphorylationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein polyubiquitinationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
mitotic spindle organizationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein transportPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
Wnt signaling pathwayPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
regulation of telomere maintenance via telomerasePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
positive regulation of telomere maintenance via telomerasePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
positive regulation of transcription by RNA polymerase IIPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
mRNA transportPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
spindle assemblyPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
cell divisionPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
positive regulation of telomerase activityPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein localization to chromosome, telomeric regionPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein poly-ADP-ribosylationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein auto-ADP-ribosylationPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
positive regulation of canonical Wnt signaling pathwayPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
positive regulation of telomere cappingPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
negative regulation of telomere maintenance via telomere lengtheningPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
negative regulation of telomeric DNA bindingPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
negative regulation of maintenance of mitotic sister chromatid cohesion, telomericPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
DNA damage responsePoly [ADP-ribose] polymerase 1Homo sapiens (human)
mitochondrion organizationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
mitochondrial DNA metabolic processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
regulation of protein localizationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to oxidative stressPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein modification processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
mitochondrial DNA repairPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of transcription by RNA polymerase IIPoly [ADP-ribose] polymerase 1Homo sapiens (human)
telomere maintenancePoly [ADP-ribose] polymerase 1Homo sapiens (human)
DNA repairPoly [ADP-ribose] polymerase 1Homo sapiens (human)
double-strand break repairPoly [ADP-ribose] polymerase 1Homo sapiens (human)
transcription by RNA polymerase IIPoly [ADP-ribose] polymerase 1Homo sapiens (human)
apoptotic processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
DNA damage responsePoly [ADP-ribose] polymerase 1Homo sapiens (human)
transforming growth factor beta receptor signaling pathwayPoly [ADP-ribose] polymerase 1Homo sapiens (human)
response to gamma radiationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of cardiac muscle hypertrophyPoly [ADP-ribose] polymerase 1Homo sapiens (human)
carbohydrate biosynthetic processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein autoprocessingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
signal transduction involved in regulation of gene expressionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
macrophage differentiationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
DNA ADP-ribosylationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of DNA-templated transcription, elongationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to insulin stimulusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of intracellular estrogen receptor signaling pathwayPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of transcription elongation by RNA polymerase IIPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to UVPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of canonical NF-kappaB signal transductionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
innate immune responsePoly [ADP-ribose] polymerase 1Homo sapiens (human)
regulation of circadian sleep/wake cycle, non-REM sleepPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of innate immune responsePoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of DNA-templated transcriptionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of transcription by RNA polymerase IIPoly [ADP-ribose] polymerase 1Homo sapiens (human)
decidualizationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
regulation of catalytic activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of mitochondrial depolarizationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of SMAD protein signal transductionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of necroptotic processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein poly-ADP-ribosylationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein auto-ADP-ribosylationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein localization to chromatinPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to zinc ionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
replication fork reversalPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of cGAS/STING signaling pathwayPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of protein localization to nucleusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathwayPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of single strand break repairPoly [ADP-ribose] polymerase 1Homo sapiens (human)
response to aldosteronePoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of adipose tissue developmentPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of telomere maintenance via telomere lengtheningPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to amyloid-betaPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of myofibroblast differentiationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
regulation of base-excision repairPoly [ADP-ribose] polymerase 1Homo sapiens (human)
positive regulation of double-strand break repair via homologous recombinationPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cellular response to nerve growth factor stimulusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
ATP generation from poly-ADP-D-ribosePoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of ATP biosynthetic processPoly [ADP-ribose] polymerase 1Homo sapiens (human)
negative regulation of gene expressionProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
positive regulation of tyrosine phosphorylation of STAT proteinProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
negative regulation of tyrosine phosphorylation of STAT proteinProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
innate immune responseProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
negative regulation of DNA-templated transcriptionProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
negative regulation of type II interferon-mediated signaling pathwayProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
positive regulation of interleukin-4-mediated signaling pathwayProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
protein poly-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
chromatin organizationProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
negative regulation of gene expressionProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
viral protein processingProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
translesion synthesisProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
negative regulation of NF-kappaB transcription factor activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
NAD biosynthesis via nicotinamide riboside salvage pathwayProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
negative regulation of DNA-templated transcriptionProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
negative regulation of fibroblast proliferationProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
protein poly-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
protein auto-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
negative regulation of protein K63-linked ubiquitinationProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
viral protein processingProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
endoplasmic reticulum unfolded protein responseProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
NAD biosynthesis via nicotinamide riboside salvage pathwayProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
IRE1-mediated unfolded protein responseProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
protein auto-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
cellular response to leukemia inhibitory factorProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
negative regulation of cytoplasmic translationProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
protein auto-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
protein polyubiquitinationPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
Wnt signaling pathwayPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
positive regulation of telomere maintenance via telomerasePoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
protein localization to chromosome, telomeric regionPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
protein poly-ADP-ribosylationPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
protein auto-ADP-ribosylationPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
positive regulation of canonical Wnt signaling pathwayPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
positive regulation of telomere cappingPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
negative regulation of telomere maintenance via telomere lengtheningPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
DNA repairPoly [ADP-ribose] polymerase 2Homo sapiens (human)
base-excision repairPoly [ADP-ribose] polymerase 2Homo sapiens (human)
DNA damage responsePoly [ADP-ribose] polymerase 2Homo sapiens (human)
DNA ADP-ribosylationPoly [ADP-ribose] polymerase 2Homo sapiens (human)
decidualizationPoly [ADP-ribose] polymerase 2Homo sapiens (human)
positive regulation of cell growth involved in cardiac muscle cell developmentPoly [ADP-ribose] polymerase 2Homo sapiens (human)
protein poly-ADP-ribosylationPoly [ADP-ribose] polymerase 2Homo sapiens (human)
protein auto-ADP-ribosylationPoly [ADP-ribose] polymerase 2Homo sapiens (human)
response to oxygen-glucose deprivationPoly [ADP-ribose] polymerase 2Homo sapiens (human)
extrinsic apoptotic signaling pathwayPoly [ADP-ribose] polymerase 2Homo sapiens (human)
hippocampal neuron apoptotic processPoly [ADP-ribose] polymerase 2Homo sapiens (human)
DNA repair-dependent chromatin remodelingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
double-strand break repairPoly [ADP-ribose] polymerase 2Homo sapiens (human)
DNA repairProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
inflammatory responseProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
DNA damage responseProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
response to xenobiotic stimulusProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
protein modification processProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
regulation of telomerase activityProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
protein poly-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
telomere maintenanceProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
double-strand break repairProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
positive regulation of DNA ligationProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
regulation of mitotic spindle organizationProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
protein localization to site of double-strand breakProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
DNA ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
negative regulation of isotype switchingProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
protein auto-ADP-ribosylationProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
negative regulation of telomerase RNA reverse transcriptase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
positive regulation of double-strand break repair via nonhomologous end joiningProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
double-strand break repairProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (42)

Processvia Protein(s)Taxonomy
NAD+ ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
protein bindingPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
zinc ion bindingPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nucleotidyltransferase activityPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
histone bindingPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
DNA bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
chromatin bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
damaged DNA bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
RNA bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
zinc ion bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleotidyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
enzyme bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein kinase bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nuclear estrogen receptor bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleosome bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
ubiquitin protein ligase bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
identical protein bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein homodimerization activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
histone deacetylase bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
R-SMAD bindingPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD DNA ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
transcription regulator activator activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-protein-serine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+- protein-aspartate ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-protein-glutamate ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-protein-tyrosine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-protein-histidine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-histone H2BS6 serine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-histone H3S10 serine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-histone H2BE35 glutamate ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 1Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
protein bindingProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
enzyme bindingProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
transcription corepressor activityProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
protein bindingProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
K63-linked polyubiquitin modification-dependent protein bindingProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
DNA-binding transcription factor bindingProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
NAD+- protein-lysine ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
transcription corepressor activityProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
protein bindingProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
kinase bindingProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
protein serine/threonine kinase activator activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
NAD+- protein-lysine ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
NAD+- protein-aspartate ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
NAD+-protein-glutamate ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
RNA bindingProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
metal ion bindingProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
NAD+- protein-cysteine ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
protein bindingPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
nucleotidyltransferase activityPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
enzyme bindingPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
metal ion bindingPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
chromatin bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
damaged DNA bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
protein bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleotidyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleosome bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
poly-ADP-D-ribose bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD DNA ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD+-protein-serine ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD+- protein-aspartate ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD+-protein-glutamate ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
poly-ADP-D-ribose modification-dependent protein bindingPoly [ADP-ribose] polymerase 2Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityPoly [ADP-ribose] polymerase 2Homo sapiens (human)
DNA bindingProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
protein bindingProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
enzyme bindingProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
catalytic activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD+ ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
protein bindingProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
nucleotidyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD DNA ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD+- protein-lysine ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD+- protein-aspartate ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD+-protein-glutamate ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
NAD+-protein ADP-ribosyltransferase activityProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (34)

Processvia Protein(s)Taxonomy
Golgi membranePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
pericentriolar materialPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
chromosome, telomeric regionPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nucleoplasmPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
Golgi apparatusPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
cytosolPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nuclear bodyPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nuclear membranePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
mitotic spindle polePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nuclear porePoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
cytoplasmPoly [ADP-ribose] polymerase tankyrase-1Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cytosolPoly [ADP-ribose] polymerase 1Homo sapiens (human)
site of double-strand breakPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nuclear replication forkPoly [ADP-ribose] polymerase 1Homo sapiens (human)
site of DNA damagePoly [ADP-ribose] polymerase 1Homo sapiens (human)
chromosome, telomeric regionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nuclear envelopePoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleoplasmPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleolusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
mitochondrionPoly [ADP-ribose] polymerase 1Homo sapiens (human)
membranePoly [ADP-ribose] polymerase 1Homo sapiens (human)
nuclear bodyPoly [ADP-ribose] polymerase 1Homo sapiens (human)
site of double-strand breakPoly [ADP-ribose] polymerase 1Homo sapiens (human)
site of DNA damagePoly [ADP-ribose] polymerase 1Homo sapiens (human)
chromatinPoly [ADP-ribose] polymerase 1Homo sapiens (human)
transcription regulator complexPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein-containing complexPoly [ADP-ribose] polymerase 1Homo sapiens (human)
protein-DNA complexPoly [ADP-ribose] polymerase 1Homo sapiens (human)
nucleolusPoly [ADP-ribose] polymerase 1Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
cytosolProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
plasma membraneProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
membraneProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
nucleusProtein mono-ADP-ribosyltransferase PARP14Homo sapiens (human)
nucleusProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
nucleolusProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
Golgi apparatusProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
cytosolProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
nucleusProtein mono-ADP-ribosyltransferase PARP10Homo sapiens (human)
nuclear envelopeProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
endoplasmic reticulumProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
endoplasmic reticulum membraneProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
cytosolProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
membraneProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
endoplasmic reticulum tubular networkProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
nuclear envelopeProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
endoplasmic reticulum tubular networkProtein mono-ADP-ribosyltransferase PARP16Homo sapiens (human)
nucleusProtein mono-ADP-ribosyltransferase PARP12Homo sapiens (human)
Golgi membranePoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
pericentriolar materialPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
chromosome, telomeric regionPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
nuclear envelopePoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
cytoplasmPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
cytosolPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
perinuclear region of cytoplasmPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
cytoplasmPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase tankyrase-2Homo sapiens (human)
site of DNA damagePoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleusPoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleoplasmPoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleolusPoly [ADP-ribose] polymerase 2Homo sapiens (human)
site of DNA damagePoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleolusPoly [ADP-ribose] polymerase 2Homo sapiens (human)
nucleusProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
nucleoplasmProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
cytosolProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
spindle microtubuleProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
membraneProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
extracellular exosomeProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
ribonucleoprotein complexProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP4Homo sapiens (human)
nucleoplasmProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
cytoplasmProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
centrosomeProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
centrioleProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
nuclear bodyProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
site of double-strand breakProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
intercellular bridgeProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
nucleolusProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
site of double-strand breakProtein mono-ADP-ribosyltransferase PARP3Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (215)

Assay IDTitleYearJournalArticle
AID1347125qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347139qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347122qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347128qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347111qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347112qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347109qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347141qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347113qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347126qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347140qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347118qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347135qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347114qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347115qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347123qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347110qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347124qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID686947qHTS for small molecule inhibitors of Yes1 kinase: Primary Screen2013Bioorganic & medicinal chemistry letters, Aug-01, Volume: 23, Issue:15
Identification of potent Yes1 kinase inhibitors using a library screening approach.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347121qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347127qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347116qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347129qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347117qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347138qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D caspase screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347119qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347136qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347137qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Orthogonal 3D viability screen for Daoy cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1895781Binding affinity to PARP5a (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID348254Potentiation of cyclophosphamide-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 5 mg/kg/day, sc osmotic minipump after 48 days relative to cyclophosphamide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412652Inhibition of human recombinant PARP22009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1428388Inhibition of recombinant human His6-tagged PARP2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1240632Binding affinity to recombinant human HisGST-tagged PARP-1 catalytic domain by surface plasmon resonance analysis2015Journal of medicinal chemistry, Sep-10, Volume: 58, Issue:17
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.
AID348243Antitumor activity against mouse B16F10 cells xenografted in C57BL/6 mouse assessed as tumor volume at 12.5 mg/kg/day, po after 14 days2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895766Inhibition of human recombinant N-terminal 6His-6Lys-TEV tagged PARP1 full length expressed in pFastBac expression system incubated for 4 hrs by fluorescence anisotropy binding assay2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1631790Cytotoxicity against human HCT116 cells by SRB assay2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors.
AID348224Cmax in cynomolgus monkey at 2.5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412657Cmax in CD1 mouse at 10 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID762672Inhibition of human PARP1 catalytic activity after 10 mins by ELISA2013Bioorganic & medicinal chemistry letters, Aug-15, Volume: 23, Issue:16
Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors.
AID1872300Inhibition of PARP2 (unknown origin)2022European journal of medicinal chemistry, Feb-15, Volume: 230Recent advances in DDR (DNA damage response) inhibitors for cancer therapy.
AID1632631Growth inhibition of human SW620 cells after 72 hrs by SRB assay2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1428384Inhibition of full length recombinant human His6-tagged PARP1 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1428393Inhibition of recombinant human TNKS2 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID348220Clearance in Beagle dog at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412662AUC in Sprague-Dawley rat at 5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348237Protein binding in Sprague-Dawley rat plasma at 5 uM2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1428395Inhibition of recombinant human His6-tagged PARP10 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID441940Inhibition of PARP1 by scintillation counting2009Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21
Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents.
AID1631788Inhibition of PARP1 (unknown origin)2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors.
AID1428394Inhibition of full length recombinant human His6-tagged PARP10 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1064455Inhibition of GST-tagged recombinant human PARP-1 expressed in Escherichia coli after 30 mins by fluorescence-based assay2014Bioorganic & medicinal chemistry letters, Jan-15, Volume: 24, Issue:2
Novel PARP-1 inhibitors based on a 2-propanoyl-3H-quinazolin-4-one scaffold.
AID1428385Inhibition of recombinant human His6-tagged PARP1 C-3-zinc finger domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID348225Volume of distribution at steady state in cynomolgus monkey at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412649Potentiation of carboplatin-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 50 mg/kg/day, sc osmotic minipump after 42 days relative to carboplatin monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1508852Inhibition of human full-length N-terminal GST-tagged PARP1 expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
AID441941Inhibition of PARP1 in human C41 cells after 30 mins by cell-based assay2009Journal of medicinal chemistry, Nov-12, Volume: 52, Issue:21
Synthesis and evaluation of a new generation of orally efficacious benzimidazole-based poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors as anticancer agents.
AID1179161Toxicity in refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 50 mg cyclophosphamide once daily administered on days 1 to 52014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID1632633Growth inhibition of human MDA-MB-468 cells after 72 hrs by SRB assay2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID412658Volume of distribution at steady state in CD1 mouse at 10 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1179162Toxicity in refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 0.6 mg/m2/day, iv topotecan administered on days 1 to 52014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID1064618Antiproliferative activity against BRCA2 gene mutated human Capan1 cells after 72 hrs by SRB assay2014Bioorganic & medicinal chemistry, Feb-01, Volume: 22, Issue:3
7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors.
AID348253Potentiation of carboplatin-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 5 mg/kg/day, sc osmotic minipump after 42 days relative to carboplatin monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1064835Inhibition of human 6xhis-tagged ARTD5 (1030 to 1317) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate at 10 uM by fluorescence assay relative to control2014ACS medicinal chemistry letters, Jan-09, Volume: 5, Issue:1
Evaluation and Structural Basis for the Inhibition of Tankyrases by PARP Inhibitors.
AID348213Volume of distribution at steady state in Sprague-Dawley rat at 5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1428387Inhibition of full length recombinant human His6-tagged PARP2 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1428397Inhibition of recombinant human His6-tagged PARP14 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID348229Inhibition of CYP2A6 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348250Potentiation of temozolomide-induced cytotoxicity against mouse B16F10 cells xenografted in C57BL/6 mouse assessed as growth inhibition at 1 mg/kg/day, po after 17 days relative to temozolomide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1064606Antiproliferative activity against BRCA1 gene mutated human HCC1937 cells after 72 hrs by SRB assay2014Bioorganic & medicinal chemistry, Feb-01, Volume: 22, Issue:3
7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors.
AID1276413Inhibition of human PARP1 using [3H]NAD as substrate after 1 min by microplate scintillation counting analysis2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID1403931Inhibition of recombinant human PARP1 using histone as substrate after 1 hr in presence of NAD+ by ELISA2018European journal of medicinal chemistry, Feb-10, Volume: 145Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors.
AID1508890Inhibition of human PARP2 expressed in Escherichia coli using biotinylated histone H1 as substrate measured in presence of [3H]NAD+ by topcount scintillation counting method
AID1631792Inhibition of PARP1 in human A549 cells assessed as potentiation of TMZ-mediated cytotoxicity by measuring TMZ IC50 for growth inhibition at 0.5 uM by SRB assay (Rvb TMZ IC50 = 295 uM)2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors.
AID348255Potentiation of cyclophosphamide-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 12.5 mg/kg/day, sc osmotic minipump after 48 days relative to cyclophosphamide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1428398Inhibition of recombinant human His6-tagged PARP15 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1895770Antiproliferative activity against human DLD-1 deficient in BRCA-2 cells measured after 7 days2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1895783Binding affinity to PARP7 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID762670Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay in presence of 100 uM of temozolomide2013Bioorganic & medicinal chemistry letters, Aug-15, Volume: 23, Issue:16
Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors.
AID1632636Inhibition of PARP-1 in human A549 cells assessed as potentiation of temozolomide induced growth inhibition by measuring ratio of temozolomide EC50 at 0.5 uM after 72 hrs by SRB assay relative to control2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1632634Inhibition of PARP-1 in human MDA-MB-468 cells assessed as potentiation of temozolomide induced growth inhibition by measuring ratio of temozolomide EC50 at 0.5 uM after 72 hrs by SRB assay relative to control2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1895786Binding affinity to PARP10 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID412653Inhibition of PARP1 in human C41 cells2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1632632Growth inhibition of human MDA-MB-468 cells at 100 uM after 72 hrs by SRB assay2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1631793Inhibition of PARP1 in human A549 cells assessed as potentiation of TMZ-mediated cytotoxicity at 0.5 uM by SRB assay2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors.
AID348233Inhibition of CYP2E1 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1631789Inhibition of PARP1 (unknown origin) at 100 nM2016Bioorganic & medicinal chemistry letters, 08-15, Volume: 26, Issue:16
Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors.
AID348232Inhibition of CYP2C19 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348222Half life in cynomolgus monkey at 2.5 mg/kg, iv2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1179165In vivo inhibition of PARP activity in peripheral blood mononuclear cells of refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 0.6 mg/m2/day, iv topotecan administered on days 1 to 52014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID348217AUC in Beagle dog at 2.5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1403934Cytotoxicity against Chinese hamster V79 cells at 10 uM after 3 days by CCK8 assay2018European journal of medicinal chemistry, Feb-10, Volume: 145Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors.
AID1428396Inhibition of recombinant human His6-tagged PARP12 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1895782Binding affinity to PARP5b (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID762671Inhibition of PARP1 in human Jurkat cells assessed as reduction of cell viability after 96 hrs by MTS assay2013Bioorganic & medicinal chemistry letters, Aug-15, Volume: 23, Issue:16
Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors.
AID1895777Binding affinity to PARP1 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1428391Inhibition of recombinant human TNKS1 ADP-ribosyltransferase/sterile alpha motif domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1276416Inhibition of PARP in human LoVo cells assessed as inhibition of poly(ADP)-ribose polymerization for 30 mins by fluorescence assay2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID1895784Binding affinity to PARP8 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1895791Binding affinity to PARP1 (unknown origin) assessed as residence time2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1428386Inhibition of recombinant human His6-tagged PARP1 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1895785Binding affinity to PARP9 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1155631Cytotoxicity against chicken wild-type DT40 cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay2014Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13
Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.
AID1895789Binding affinity to PARP14 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID348216Half life in Beagle dog at 2.5 mg/kg, iv2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348227Water solubility of compound at physiological pH2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID762669Chemopotentiation factor, ratio of EC50 for PARP1 in human Jurkat cells to EC50 for PARP1 in human Jurkat cells in presence of 100 uM of temozolomide2013Bioorganic & medicinal chemistry letters, Aug-15, Volume: 23, Issue:16
Discovery of novel benzo[b][1,4]oxazin-3(4H)-ones as poly(ADP-ribose)polymerase inhibitors.
AID412650Potentiation of carboplatin-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 25 mg/kg/day, sc osmotic minipump after 42 days relative to carboplatin monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348226Clearance in cynomolgus monkey at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412659Clearance in CD1 mouse at 10 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895779Binding affinity to PARP3 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1403933Cytotoxicity against Chinese hamster VC8 cells harboring BRCA2 deficient after 3 days by CCK8 assay2018European journal of medicinal chemistry, Feb-10, Volume: 145Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors.
AID1179160Half life in refractory solid tumor and lymphoma patient2014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID1474432Inhibition of recombinant human PARP1 expressed in Escherichia coli BL21(DE3) using histone as substrate measured after 1 hr in presence of biotinylated NAD+ by ELISA2017European journal of medicinal chemistry, May-26, Volume: 132Discovery of 2-substituted 1H-benzo[d]immidazole-4-carboxamide derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors with in vivo anti-tumor activity.
AID1508854Inhibition of human N-terminal GST-tagged PARP2 (2 to 583 residues) expressed in baculovirus infected Sf9 insect cells using histone as substrate measured after 1 hr by horseradish peroxidase-coupled chemiluminescence assay
AID1234864Inhibition of PARP-1 (unknown origin) assessed as incorporation of biotinylated poly (ADP-ribose) onto histone protein after 60 mins by TACS-Sapphire substarte-based colorimetric analysis2015Bioorganic & medicinal chemistry, Aug-01, Volume: 23, Issue:15
Benzimidazole derivatives as potential dual inhibitors for PARP-1 and DHODH.
AID1428399Inhibition of full length recombinant human His6-tagged PARP16 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1240634Binding affinity to recombinant human HisGST-tagged PARP-2 catalytic domain by surface plasmon resonance analysis2015Journal of medicinal chemistry, Sep-10, Volume: 58, Issue:17
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.
AID1683865Inhibition of human PARP-1 catalytic domain (662 to 1011 residues) expressed in Escherichia coli BL21(DE3) cells incubated for 0.5 hrs by fluorescence polarization assay based DNA trapping activity assay2020Journal of medicinal chemistry, 12-24, Volume: 63, Issue:24
Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development.
AID412656AUC in CD1 mouse at 10 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348215Oral bioavailability in Beagle dog at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348219Volume of distribution at steady state in Beagle dog at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348230Inhibition of CYP2D6 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348244Antitumor activity against mouse B16F10 cells xenografted in C57BL/6 mouse assessed as growth inhibition at 12.5 mg/kg/day, po after 14 days relative to control2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1240633Binding affinity to recombinant human HisGST-tagged PARP-1 catalytic domain assessed as dissociation half life by surface plasmon resonance analysis2015Journal of medicinal chemistry, Sep-10, Volume: 58, Issue:17
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.
AID1155633Cytotoxicity against chicken BRCA2-deficient DT40 cells assessed as cell viability after 72 hrs by ATPlite assay2014Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13
Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.
AID1155632Cytotoxicity against chicken PARP1-deficient DT40 cells assessed as cell viability at 10 uM after 72 hrs by ATPlite assay2014Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13
Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.
AID412654Oral bioavailability in CD1 mouse at 10 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1276422Cytotoxicity against human MRC5 cells2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID1895790Binding affinity to PARP16 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1155630Inhibition of PARP-1 (unknown origin) using biotinylated NAD+ as substrate after 60 mins by spectrophotometry2014Journal of medicinal chemistry, Jul-10, Volume: 57, Issue:13
Discovery and structure-activity relationship of novel 2,3-dihydrobenzofuran-7-carboxamide and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide derivatives as poly(ADP-ribose)polymerase-1 inhibitors.
AID1064834Inhibition of human 6xhis-tagged ARTD5 (1030 to 1317) expressed in Escherichia coli Rosetta2 (DE3) cells using NAD+ as substrate by fluorescence assay2014ACS medicinal chemistry letters, Jan-09, Volume: 5, Issue:1
Evaluation and Structural Basis for the Inhibition of Tankyrases by PARP Inhibitors.
AID348234Inhibition of CYP3A4 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1632628Inhibition of PARP-1 (unknown origin) after 1 hr in presence of NAD+/biotinylated NAD+/slDNA by ELISA2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1895787Binding affinity to PARP11 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1403932Inhibition of recombinant human PARP2 using histone as substrate after 1.5 hr in presence of NAD+ by ELISA2018European journal of medicinal chemistry, Feb-10, Volume: 145Design and synthesis of 2-(4,5,6,7-tetrahydrothienopyridin-2-yl)-benzoimidazole carboxamides as novel orally efficacious Poly(ADP-ribose)polymerase (PARP) inhibitors.
AID1428390Inhibition of recombinant human His6-tagged PARP4 ADP-ribosyltransferase domain expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1632630Growth inhibition of human SW620 cells at 100 uM after 72 hrs by SRB assay2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID348231Inhibition of CYP2C9 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895769Inhibition of human recombinant PARP5a (E1023 to T1327 amino acids) incubated for 4 hrs by fluorescence anisotropy binding assay2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID412661Half life in Sprague-Dawley rat at 5 mg/kg, iv2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID739045Inhibition of PARP1 (unknown origin)2013Bioorganic & medicinal chemistry letters, Apr-01, Volume: 23, Issue:7
Design, synthesis and biological evaluation of novel imidazo[4,5-c]pyridinecarboxamide derivatives as PARP-1 inhibitors.
AID348221Oral bioavailability in cynomolgus monkey at 2.5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348228Inhibition of CYP1A2 in human liver microsomes2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1179166In vivo inhibition of PARP activity in tumor tissue of refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 0.6 mg/m2/day, iv topotecan administered on days 1 to 52014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID1064607Inhibition of recombinant human GST-fused PARP-1 expressed in Escherichia coli after 30 mins by fluorescence assay2014Bioorganic & medicinal chemistry, Feb-01, Volume: 22, Issue:3
7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors.
AID1872299Inhibition of PARP1 (unknown origin)2022European journal of medicinal chemistry, Feb-15, Volume: 230Recent advances in DDR (DNA damage response) inhibitors for cancer therapy.
AID348248Potentiation of temozolomide-induced cytotoxicity against mouse B16F10 cells xenografted in C57BL/6 mouse assessed as growth inhibition at 12.5 mg/kg/day, po after 17 days relative to temozolomide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1179164In vivo inhibition of PARP activity in tumor tissue of refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 50 mg cyclophosphamide once daily administered on days 1 to 52014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID348236Protein binding in CD1 mouse plasma at 5 uM2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895788Binding affinity to PARP12 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1895768Selectivity ratio of IC50 for PARP1 (unknown origin) to IC50 for PARP2 (unknown origin )2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID412655Half life in CD1 mouse at 3 mg/kg, iv2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1632635Inhibition of PARP-1 in human SW620 cells assessed as potentiation of temozolomide induced growth inhibition by measuring ratio of temozolomide EC50 at 0.5 uM after 72 hrs by SRB assay relative to control2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID348214Clearance in Sprague-Dawley rat at 5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1508889Inhibition of human PARP1 expressed in Escherichia coli using biotinylated histone H1 as substrate measured in presence of [3H]NAD+ by topcount scintillation counting method
AID348218Cmax in Beagle dog at 2.5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1428389Inhibition of full length recombinant human His6-tagged PARP3 expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotinylated NAD+ addition by chemiluminescence assay2017Journal of medicinal chemistry, 02-23, Volume: 60, Issue:4
Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.
AID1240635Binding affinity to recombinant human HisGST-tagged PARP-2 catalytic domain assessed as dissociation half life by surface plasmon resonance analysis2015Journal of medicinal chemistry, Sep-10, Volume: 58, Issue:17
Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy.
AID412651Inhibition of human recombinant PARP12009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1474435Inhibition of recombinant human PARP1 expressed in Escherichia coli BL21(DE3) using sheared DNA as substrate measured after 1 hr in presence of NAD+2017European journal of medicinal chemistry, May-26, Volume: 132Discovery of 2-substituted 1H-benzo[d]immidazole-4-carboxamide derivatives as novel poly(ADP-ribose)polymerase-1 inhibitors with in vivo anti-tumor activity.
AID348238Protein binding in Beagle dog plasma at 5 uM2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID412663Cmax in Sprague-Dawley rat at 5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID348251Potentiation of carboplatin-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 1 mg/kg/day, sc osmotic minipump after 42 days relative to carboplatin monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID739046Inhibition of PARP1 (unknown origin) at 1 uM2013Bioorganic & medicinal chemistry letters, Apr-01, Volume: 23, Issue:7
Design, synthesis and biological evaluation of novel imidazo[4,5-c]pyridinecarboxamide derivatives as PARP-1 inhibitors.
AID348252Potentiation of carboplatin-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 12.5 mg/kg/day, sc osmotic minipump after 42 days relative to carboplatin monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1879929In vivo rescue of F508del-CFTR activity in cystic fibrosis mouse model assessed as measuring salivary secretion at 5 mg/kg/day, ip qd for 2 days relative to control2022Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7
Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.
AID348223AUC in cynomolgus monkey at 2.5 mg/kg, po2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1179163In vivo inhibition of PARP activity in peripheral blood mononuclear cells of refractory solid tumor and lymphoma patient at 10 mg dosed twice daily on days 1 to 5 in 21-day cycles co-treated with 50 mg cyclophosphamide once daily administered on days 1 to2014Journal of medicinal chemistry, Oct-09, Volume: 57, Issue:19
Development of synthetic lethality anticancer therapeutics.
AID348249Potentiation of temozolomide-induced cytotoxicity against mouse B16F10 cells xenografted in C57BL/6 mouse assessed as growth inhibition at 5 mg/kg/day, po after 17 days relative to temozolomide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895778Binding affinity to PARP2 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1276419Cytotoxicity against BRCA2-deficient human Capan1 cells2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID348256Potentiation of cyclophosphamide-induced cytotoxicity against human MX1 cells xenografted in SCID mouse assessed as growth inhibition at 25 mg/kg/day, sc osmotic minipump after 48 days relative to cyclophosphamide monotherapy2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895767Inhibition of human recombinant N-terminal Avi-6His-TEV tagged PARP2 full length expressed in pFastBac expression system incubated for 4 hrs by fluorescence anisotropy binding assay2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID348235Protein binding in human plasma at 5 uM2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1276417Potentiation of temozolomide-induced cytotoxicity in human LoVo cells assessed as temozolomide GI50 at 0.4 uM after 5 days by Celltiter-Glo assay2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID348239Protein binding in cynomolgus monkey plasma at 5 uM2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1895780Binding affinity to PARP4 (unknown origin) assessed as apparent dissociation constant2021Journal of medicinal chemistry, 10-14, Volume: 64, Issue:19
Discovery of 5-{4-[(7-Ethyl-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl]piperazin-1-yl}-
AID1276421Cytotoxicity against BRCA1-deficient human MX1 cells2016Journal of medicinal chemistry, Jan-14, Volume: 59, Issue:1
Discovery and Characterization of (8S,9R)-5-Fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-2,7,8,9-tetrahydro-3H-pyrido[4,3,2-de]phthalazin-3-one (BMN 673, Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymer
AID1879928Ex vivo inhibition of PARP-1 in ileum of cystic fibrosis mouse model assessed as rescue of F508del-CFTR activity at 1 nM treated for 4 hrs in presence of forskolin/genistein relative to control2022Journal of medicinal chemistry, 04-14, Volume: 65, Issue:7
Proteostasis Regulators in Cystic Fibrosis: Current Development and Future Perspectives.
AID412660Oral bioavailability in Sprague-Dawley rat at 5 mg/kg2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1632629Inhibition of PARP-2 (unknown origin) after 1 hr in presence of NAD+/biotinylated NAD+/slDNA by ELISA2016Bioorganic & medicinal chemistry, 10-01, Volume: 24, Issue:19
Novel tricyclic poly (ADP-ribose) polymerase-1/2 inhibitors with potent anticancer chemopotentiating activity: Design, synthesis and biological evaluation.
AID1745855NCATS anti-infectives library activity on the primary C. elegans qHTS viability assay2023Disease models & mechanisms, 03-01, Volume: 16, Issue:3
In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
AID1745854NCATS anti-infectives library activity on HEK293 viability as a counter-qHTS vs the C. elegans viability qHTS2023Disease models & mechanisms, 03-01, Volume: 16, Issue:3
In vivo quantitative high-throughput screening for drug discovery and comparative toxicology.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1798781In Vitro PARP Enzyme Assay from Article 10.1021/jm801171j: \\Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.\\2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
AID1802336In Vitro PARP1 Activity Assay from Article 10.1016/j.chembiol.2016.10.011: \\Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets.\\2016Cell chemical biology, Dec-22, Volume: 23, Issue:12
Proteome-wide Profiling of Clinical PARP Inhibitors Reveals Compound-Specific Secondary Targets.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (319)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's24 (7.52)29.6817
2010's223 (69.91)24.3611
2020's72 (22.57)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials87 (26.77%)5.53%
Reviews27 (8.31%)6.00%
Case Studies2 (0.62%)4.05%
Observational0 (0.00%)0.25%
Other209 (64.31%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (104)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
NCI 10147: A Phase II Randomized Study of Topotecan/Carboplatin With or Without Veliparib in Advanced Myeloproliferative Disorders and Chronic Myelomonocytic Leukemia (CMML) [NCT03289910]Phase 260 participants (Anticipated)Interventional2018-06-08Active, not recruiting
Phase I Study of ABT-888 in Combination With Gemcitabine in Patients With Advanced Malignancies [NCT01154426]Phase 131 participants (Actual)Interventional2010-05-31Completed
Randomized Phase II Study of 2nd Line FOLFIRI Versus Modified FOLFIRI With PARP Inhibitor ABT-888 (Veliparib) (NSC-737664) in Metastatic Pancreatic Cancer [NCT02890355]Phase 2123 participants (Actual)Interventional2016-09-01Active, not recruiting
A Phase I Study of a Combination of MM-398 and Veliparib in Solid Tumors [NCT02631733]Phase 148 participants (Anticipated)Interventional2017-05-31Active, not recruiting
Phase II Randomized Placebo-Controlled Trial of Cisplatin With or Without ABT-888 (Veliparib) in Metastatic Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer, With or Without Brain Metastases [NCT02595905]Phase 2333 participants (Anticipated)Interventional2016-09-15Active, not recruiting
A Dose Finding Study Followed by Phase II Randomized, Placebo-Controlled Study of Veliparib (ABT-888) Added to Chemoradiotherapy With Carboplatin and Paclitaxel for Unresectable Stage III Non-small Cell Lung Cancer (NSCLC), (NCI Study Number 8811) [NCT01386385]Phase 1/Phase 253 participants (Actual)Interventional2011-06-20Active, not recruiting
Phase I Study of ABT-888, PARP Inhibitor, and Pegylated Liposomal Doxorubicin (PLD) in Recurrent Gynecologic Cancer and Breast Cancer [NCT01145430]Phase 145 participants (Actual)Interventional2010-06-01Completed
Phase I and Randomized Phase II Double Blind Clinical Trial of Cisplatin and Etoposide in Combination With Veliparib (ABT-888) or Placebo as Frontline Therapy for Extensive Stage Small Cell Lung Cancer [NCT01642251]Phase 1/Phase 2156 participants (Actual)Interventional2012-09-28Completed
A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors [NCT01281150]Phase 122 participants (Actual)Interventional2011-01-31Completed
A Limited Access Phase I Trial of Paclitaxel, Cisplatin and CTEP Supplied Agent ABT-888 (Veliparib) (NSC#737664) in the Treatment of Advanced, Persistent, or Recurrent Carcinoma of the Cervix [NCT01281852]Phase 137 participants (Actual)Interventional2011-03-14Completed
Pre-Operative PARPi and Irradiation (POPI) in Women With an Incomplete Response to Neo-Adjuvant Chemotherapy for Breast Cancer [NCT01618357]Phase 141 participants (Anticipated)Interventional2013-07-22Suspended(stopped due to final subject consented to dose level 4)
Phase I/Ib Study of Nivolumab and Veliparib in Patients With Advanced Solid Tumors and Lymphoma With and Without Alterations in Selected DNA Repair Genes [NCT03061188]Phase 115 participants (Actual)Interventional2017-05-23Active, not recruiting
Randomized, Double-Blind, Multicenter, Phase 2 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT01560104]Phase 2160 participants (Actual)Interventional2012-02-29Completed
A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer [NCT01251874]Phase 144 participants (Actual)Interventional2010-11-16Completed
A Phase I Study of Veliparib (ABT-888) in Combination With Low-Dose Fractionated Whole Abdominal Radiation Therapy (LDFWAR) in Patients With Advanced Solid Malignancies With Peritoneal Carcinomatosis With Two Additional Dose Levels in Patients With Epithe [NCT01264432]Phase 134 participants (Actual)Interventional2011-01-01Completed
A Phase 1, Single-Dose, Randomized, Group Sequential Cross-Over Study Evaluating the Bioavailability and Food Effect of Three Formulations of Veliparib on Pharmacokinetics in Subjects With Solid Tumors [NCT01199224]Phase 127 participants (Actual)Interventional2010-06-30Completed
Phase I Study of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor in Combination With Cisplatin in Patients With Refractory Solid Tumors [NCT02723864]Phase 153 participants (Actual)Interventional2017-08-09Completed
A Phase 2 Randomized Clinical Trial of ABT-888 in Combination With Temozolomide Versus Pegylated Liposomal Doxorubicin Alone in Subjects With Recurrent High Grade Serous Ovarian Cancer [NCT01113957]Phase 2168 participants (Actual)Interventional2010-03-31Completed
An Extension Study to Evaluate the Safety of Veliparib as Single Agent Therapy or in Combination With Chemotherapy in Subjects With Solid Tumors [NCT02033551]Phase 147 participants (Actual)Interventional2013-12-31Completed
Arterial Hypertension With PARP Inhibitors in Cancer Patients: an Observational and Retrospective Study Using the WHO Pharmacovigilance Database (ArteRIB) [NCT04774406]2,336 participants (Actual)Observational2021-02-24Completed
A Phase 1 Open-Label, Dose-Escalation Study of Veliparib in Combination With Bimonthly FOLFIRI in Subjects With Advanced Solid Tumors [NCT01123876]Phase 160 participants (Actual)Interventional2010-03-31Completed
An Extension Study to Evaluate the Safety of Veliparib in Combination With Temozolomide in Subjects With Solid Tumors. [NCT01193140]Phase 224 participants (Actual)Interventional2010-07-31Completed
Phase I Study of ABT-888 in Combination With Cisplatin and Vinorelbine for Patients With Advanced Triple Negative Breast Cancer and/or BRCA-Mutation Associated Breast Cancer [NCT01104259]Phase 150 participants (Actual)Interventional2010-07-31Completed
A Phase II/III Randomized Trial of Veliparib or Placebo in Combination With Adjuvant Temozolomide in Newly Diagnosed Glioblastoma With MGMT Promoter Hypermethylation [NCT02152982]Phase 2/Phase 3447 participants (Actual)Interventional2014-12-15Active, not recruiting
A Phase I Study of ABT-888 in Combination With Oxaliplatin and Capecitabine in Advanced Solid Tumors [NCT01233505]Phase 116 participants (Actual)Interventional2010-10-31Terminated
Phase I Study of Veliparib (ABT-888) in Combination With Cisplatin Plus Gemcitabine in Advanced Biliary, Pancreatic, Urothelial, and Non-small Cell Lung Cancer [NCT01282333]Phase 144 participants (Actual)Interventional2011-01-31Terminated
A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or [NCT02470585]Phase 31,140 participants (Actual)Interventional2015-06-29Terminated(stopped due to Business decision not related to patient safety)
A Phase 1 Study of Veliparib in Combination With Carboplatin And Weekly Paclitaxel in Japanese Subjects With Ovarian Cancer [NCT02483104]Phase 19 participants (Actual)Interventional2015-07-31Completed
A Randomized Phase I/II Study of ABT-888 in Combination With Temozolomide in Recurrent (Temozolomide Resistant) Glioblastoma [NCT01026493]Phase 1/Phase 2257 participants (Actual)Interventional2010-07-31Completed
Phase II Randomized Trial of ABT-888 in Combination With Metronomic Oral Cyclophosphamide in Refractory BRCA-Positive Ovarian, Primary Peritoneal, Ovarian High-Grade Serous Carcinoma, Fallopian Tube Cancer, or Triple-Negative Breast Cancer [NCT01306032]Phase 2124 participants (Actual)Interventional2011-01-12Completed
A Phase 2 Study of ABT-888 and Temozolomide for Metastatic Breast Cancer and an Expansion Cohort in BRCA1/2 Mutation Carriers [NCT01009788]Phase 264 participants (Actual)Interventional2009-11-30Active, not recruiting
An Open-Label Phase 1b Study of the Safety and Tolerability of Veliparib in Combination With Capecitabine and Radiation in Subjects With Locally Advanced Rectal Cancer (LARC) [NCT01589419]Phase 132 participants (Actual)Interventional2012-06-30Completed
A Phase I/II Trial of Temozolomide and ABT-888 in Subjects With Newly Diagnosed Glioblastoma Multiforme [NCT00770471]Phase 124 participants (Actual)Interventional2009-07-13Completed
A Phase 1 Dose-Escalation and Phase 2 Randomized, Open-Label Study of Nivolumab and Veliparib in Combination With Platinum Doublet Chemotherapy in Subjects With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT02944396]Phase 125 participants (Actual)Interventional2016-12-23Completed
Phase II Trial of Single Agent ABT-888 With Post-Progression Therapy of ABT-888 in Combination With Carboplatin in Patients With Stage IV BRCA-Associated Breast Cancer [NCT01149083]Phase 271 participants (Anticipated)Interventional2010-06-30Active, not recruiting
A Phase 1 Study of Veliparib in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors [NCT01063816]Phase 179 participants (Actual)Interventional2010-01-31Completed
A Phase I Study of Intravenous Carboplatin/Paclitaxel or Intravenous and Intraperitoneal Paclitaxel/Cisplatin in Combination With Continuous or Intermittent /CTEP-Supplied Agent ABT-888 (NSC #737664) and CTEP-Supplied Agent Bevacizumab (NSC #704865) in Ne [NCT00989651]Phase 1431 participants (Actual)Interventional2009-10-28Completed
A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy of ABT-888 in Combination With Temozolomide Versus Temozolomide Alone in Subjects With Metastatic Melanoma [NCT00804908]Phase 2346 participants (Actual)Interventional2009-02-28Completed
A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of ABT-888 in Combination With Whole Brain Radiation Therapy in Subjects With Brain Metastases [NCT00649207]Phase 180 participants (Actual)Interventional2008-03-31Completed
A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating Safety and Efficacy of the Addition of Veliparib Plus Carboplatin Versus the Addition of Carboplatin to Standard Neoadjuvant Chemotherapy Versus Standard Neoadjuvant Chemotherapy in [NCT02032277]Phase 3634 participants (Actual)Interventional2014-04-02Completed
A Phase 1 Study of Chronically-Dosed, Single-Agent ABT-888 in Patients With Either BRCA 1/2 -Mutated Cancer; Platinum-Refractory Ovarian, Fallopian Tube, or Primary Peritoneal Cancer; or Basal-Like Breast Cancer [NCT00892736]Phase 198 participants (Actual)Interventional2009-04-20Completed
A Phase I Study of ABT-888, an Oral Inhibitor of Poly (ADP-Ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors [NCT00946335]Phase 131 participants (Actual)Interventional2009-07-31Completed
A Pilot Study Combining ABT-888, an Oral PARP Inhibitor, With Temozolomide in Patients With Metastatic Castration Resistant Prostate Cancer Who Have Failed Up to Two Non-hormonal Systemic Therapies [NCT01085422]Phase 135 participants (Actual)Interventional2010-04-30Completed
A Phase I Study of Veliparib (ABT-888) in Combination With Gemcitabine and Intensity Modulated Radiation Therapy in Patients With Locally Advanced, Unresectable Pancreatic Cancer [NCT01908478]Phase 134 participants (Actual)Interventional2013-10-02Completed
A Phase 1/2 Trial of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP), and Topotecan (TPT) in Patients With Solid Tumors (Phase 1) and Relapsed Ovarian Cancer or Primary Peritoneal Cancer (Phase 2) After Prior Platinum Containing First-Line Che [NCT01012817]Phase 1/Phase 288 participants (Actual)Interventional2009-11-03Active, not recruiting
A Randomized, Placebo-Controlled Crossover Study to Evaluate the Effect of Veliparib (ABT-888) on Cardiac Repolarization in Subjects With Relapsed or Refractory Solid Tumors [NCT02009631]Phase 145 participants (Actual)Interventional2013-11-30Completed
An Open Label, Pilot Study of Veliparib (ABT-888) and Lapatinib (Tykerb) in Patients With Metastatic, Triple Negative (ER, PR, and HER-2 Negative) Breast Cancer [NCT02158507]23 participants (Actual)Interventional2014-09-30Active, not recruiting
A Phase II Clinical Trial Platform of Sensitization Utilizing Total Neoadjuvant Therapy (TNT) in Rectal Cancer [NCT02921256]Phase 2363 participants (Actual)Interventional2017-01-11Completed
A Phase 1b/2a Study of ABT-888 in Combination With Bendamustine +/- Rituximab in Lymphoma, Multiple Myeloma and Solid Tumors [NCT01326702]Phase 1/Phase 243 participants (Actual)Interventional2011-07-31Completed
A Phase 1 Study of Veliparib (ABT-888) in Combination With Capecitabine and Temozolomide in Advanced Well-Differentiated Neuroendocrine Tumors [NCT02831179]Phase 10 participants (Actual)Interventional2017-12-31Withdrawn(stopped due to Loss of funding support)
An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors [NCT01419548]Phase 10 participants (Actual)Interventional2011-07-29Withdrawn
A Phase I Study of ABT-888 in Combination With Topotecan Hydrochloride in Adults With Refractory Solid Tumors and Lymphomas [NCT00553189]Phase 131 participants (Actual)Interventional2007-08-09Completed
A Phase 0 Pharmacokinetic, Pharmacodynamic Study of ABT-888, an Inhibitor of Poly (ADP-ribose) Polymerase (PARP), in Refractory Solid Tumors and Lymphoid Malignancies [NCT00387608]Phase 123 participants (Anticipated)Interventional2006-06-30Completed
A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-Ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors [NCT00994071]Phase 19 participants (Actual)Interventional2009-09-22Completed
ABT-888 as Monotherapy and in Combination With Mitomycin C in Patients With Solid Tumors With Deficiency in Homologous Recombination Repair [NCT01017640]Phase 120 participants (Actual)Interventional2009-10-31Completed
A Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Oral Bioavailability of Veliparib Extended Release Formulations in Subjects With Solid Tumors [NCT01853306]Phase 171 participants (Actual)Interventional2013-03-18Completed
Veliparib (ABT888) Monotherapy for Patients With BRCA Germline Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer [NCT01472783]Phase 1/Phase 249 participants (Actual)Interventional2011-11-30Completed
A Phase 1 Study of Veliparib Administered Concurrently With Chest Wall and Nodal Radiation Therapy in Patients With Inflammatory or Loco-regionally Recurrent Breast Cancer [NCT01477489]Phase 133 participants (Actual)Interventional2012-01-31Completed
A Phase I/II Study of ABT-888 in Combination With 5-fluorouracil and Oxaliplatin (Modified FOLFOX-6) in Patients With Metastatic Pancreatic Cancer [NCT01489865]Phase 1/Phase 264 participants (Actual)Interventional2011-02-28Active, not recruiting
A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies [NCT00535119]Phase 1107 participants (Actual)Interventional2007-09-30Completed
Randomized, Double-Blind, Multicenter, Phase 3 Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT02106546]Phase 3970 participants (Actual)Interventional2014-04-10Completed
A Phase II Study of ABT-888, an Inhibitor of Poly(ADP-ribose) Polymerase (PARP) in Combination With Temozolomide in Patients With Heavily Pretreated, Metastatic Colorectal Cancer [NCT01051596]Phase 275 participants (Actual)Interventional2009-09-30Completed
Phase II Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer [NCT02860819]Phase 215 participants (Actual)Interventional2016-08-01Completed
A Phase I Study of ABT-888 in Combination With Temozolomide (TMZ) in Subjects With Non-Hematologic Malignancies (NHM) and Metastatic Melanoma (MM) [NCT00526617]Phase 141 participants (Actual)Interventional2007-08-31Completed
Expanded Access to Veliparib [NCT03123211]0 participants Expanded AccessNo longer available
Phase I Study of ABT-888 in Combination With Bortezomib and Dexamethasone in Patients With Relapsed Refractory Myeloma [NCT01495351]Phase 119 participants (Actual)Interventional2011-10-31Completed
A Phase 1 Study of Veliparib (ABT-888) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Solid Tumors [NCT01617928]Phase 112 participants (Actual)Interventional2012-05-31Completed
A Phase 1 Study of Single Agent Veliparib in Japanese Subjects With Advanced Solid Tumors [NCT02210663]Phase 116 participants (Actual)Interventional2014-07-31Completed
Veliparib (ABT888) and Topotecan (Hycamtin®) for Patients With Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer With Negative or Unknown BRCA Status [NCT01690598]Phase 1/Phase 222 participants (Actual)Interventional2012-11-30Completed
A Phase I Trial of the Combination of the PARP Inhibitor ABT-888 With Intraperitoneal Floxuridine (FUDR) in Epithelial Ovarian, Primary Peritoneal and Fallopian Tube Cancers [NCT01749397]Phase 129 participants (Actual)Interventional2012-12-07Completed
Phase II Study of ABT-888 and Temozolomide in Patients With Advanced Hepatocellular Carcinoma (HCC) Progressing Following Sorafenib Treatment or Intolerant to Sorafenib [NCT01205828]Phase 216 participants (Actual)Interventional2010-08-31Terminated(stopped due to Lack of efficacy)
A Phase I Study of ABT-888 in Combination With Cyclophosphamide in Solid Tumors or Non-Hodgkin Lymphoma [NCT00740805]Phase 181 participants (Actual)Interventional2008-08-18Active, not recruiting
Randomized, Blinded, Multicenter, Phase 2 Study Comparing Veliparib Plus FOLFIRI ± Bevacizumab Versus Placebo Plus FOLFIRI ± Bevacizumab in Previously Untreated Metastatic Colorectal Cancer [NCT02305758]Phase 2130 participants (Actual)Interventional2014-12-02Completed
A Randomized Phase II Study of Gemcitabine, Cisplatin +/- Veliparib in Patients With Pancreas Adenocarcinoma and a Known BRCA/ PALB2 Mutation (Part I) and a Phase II Single Arm Study of Single-Agent Veliparib in Previously Treated Pancreas Adenocarcinoma [NCT01585805]Phase 2107 participants (Anticipated)Interventional2012-05-15Active, not recruiting
A Phase I Study of ABT-888 in Combination With Metronomic Cyclophosphamide in Adults With Refractory Solid Tumors and Lymphomas [NCT01445522]Phase 135 participants (Actual)Interventional2008-12-03Completed
I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2) [NCT01042379]Phase 25,000 participants (Anticipated)Interventional2010-03-01Recruiting
A Phase II Evaluation of ABT-888 (NCI Supplied Agent: ABT-888, NSC #737664), Topotecan (NSC # 609699) and Filgrastim or Pegfilgrastim in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix [NCT01266447]Phase 227 participants (Actual)Interventional2011-02-28Completed
Pancytopenia Related to PARP Inhibitors in Cancer Patients : an Observational and Retrospective Study Using the WHO's Pharmacovigilance Database (PancytoRIB) [NCT04774627]200 participants (Actual)Observational2021-02-07Completed
An Adaptive, Randomized Phase II Trial to Determine Pathologic Complete Response With the Addition of Carboplatin With and Without Veliparib to Standard Chemotherapy in the Neoadjuvant Treatment of Triple-Negative Breast Cancer [NCT01818063]Phase 29 participants (Actual)Interventional2013-04-25Completed
A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer [NCT02163694]Phase 3509 participants (Actual)Interventional2014-07-17Active, not recruiting
A Multi-Center, Randomized, Double-Blind Phase II Study Comparing ABT-888, a PARP Inhibitor, Versus Placebo With Temozolomide in Patients With Relapsed Sensitive or Refractory Small Cell Lung Cancer [NCT01638546]Phase 297 participants (Actual)Interventional2012-06-30Completed
A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888), and NCI Supplied Bevacizumab in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer [NCT01459380]Phase 141 participants (Actual)Interventional2011-10-11Completed
A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in S [NCT02412371]Phase 1/Phase 248 participants (Actual)Interventional2015-04-30Terminated(stopped due to Phase 2 was not conducted due to a change in the standard of care for newly diagnosed, unresectable Stage III NSCLC)
A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination With Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer [NCT02289690]Phase 1/Phase 2221 participants (Actual)Interventional2014-10-13Completed
A Phase II Evaluation of the Poly (ADP-Ribose) Polymerase (PARP)-1 and -2 Inhibitor Veliparib (ABT-888) (NSC#737664) in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients Who Carry a Germline [NCT01540565]Phase 252 participants (Actual)Interventional2012-04-09Completed
A Phase I/II Study of ABT-888, An Oral Poly(ADP-ribose) Polymerase Inhibitor, and Concurrent Radiation Therapy, Followed by ABT-888 and Temozolomide, in Children With Newly Diagnosed Diffuse Pontine Gliomas (DIPG) [NCT01514201]Phase 1/Phase 266 participants (Actual)Interventional2012-02-01Completed
A Randomized Gene Fusion Stratified Phase 2 Trial of Abiraterone With or Without ABT-888 for Patients With Metastatic Castration-Resistant Prostate Cancer [NCT01576172]Phase 2159 participants (Actual)Interventional2012-03-30Completed
Carboplatin-Paclitaxel Induction Chemotherapy and ABT-888 (Veliparib) - a Phase 1/Randomized Phase 2 Study in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT01711541]Phase 1/Phase 224 participants (Actual)Interventional2012-10-22Completed
A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination With Temozolomide or Veliparib in Combination With Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects With BRCA1 or BRCA2 Mutation [NCT01506609]Phase 2294 participants (Actual)Interventional2012-01-23Completed
Molecular Profiling-Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors [NCT01827384]Phase 2208 participants (Actual)Interventional2014-01-07Completed
A Phase 2 Study of Veliparib (ABT-888) and Local Irradiation, Followed by Maintenance Veliparib and Temozolomide, in Patients With Newly Diagnosed High-Grade Glioma (HGG) Without H3 K27M or BRAFV600 Mutations [NCT03581292]Phase 238 participants (Actual)Interventional2018-11-06Active, not recruiting
A Phase 1, Single-Dose, Open-Label, Randomized Cross-Over Study Evaluating the Bioavailability and Food Effect of Veliparib Tablets Followed by an Extension in Subjects With Ovarian Cancer [NCT03400306]Phase 10 participants (Actual)Interventional2021-11-15Withdrawn(stopped due to Strategic considerations)
Phase II Clinical Trial on the Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients With Homologous Recombination Deficiency [NCT03032614]Phase 20 participants (Actual)Interventional2017-09-30Withdrawn(stopped due to Lack of funding)
Phase II Study With PARP Inhibitor Veliparib (ABT-888) in Patients With Increased Risk of Homologous Recombination Deficiency to Determine the Value of an (Ex-vivo) RAD51 Assay as a Biomarker [NCT03044795]Phase 20 participants (Actual)Interventional2019-11-30Withdrawn(stopped due to The study never started)
A Phase I Dose-Escalation Study of Oral ABT-888 (NSC #737664) Plus Intravenous Irinotecan (CPT-11, NSC#616348) Administered in Patients With Advanced Solid Tumors [NCT00576654]Phase 136 participants (Anticipated)Interventional2007-12-05Active, not recruiting
Phase 1 Trial of ABT-888 and SCH727965 in Patients With Advanced Solid Tumors [NCT01434316]Phase 1118 participants (Anticipated)Interventional2011-11-01Active, not recruiting
An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors [NCT01366144]Phase 194 participants (Actual)Interventional2011-06-20Active, not recruiting
Phase I Trial of Low-Dose Cyclophosphamide in Combination With Veliparib (ABT-888) in HER2/Neu-Negative Metastatic Breast Cancer [NCT01351909]Phase 135 participants (Actual)Interventional2011-05-02Active, not recruiting
A Phase I Study of the PARP Inhibitor ABT-888 in Combination With Temozolomide in Acute Leukemias [NCT01139970]Phase 166 participants (Actual)Interventional2010-05-21Active, not recruiting
A Phase I Study of ABT-888 in Combination With Topotecan Plus Carboplatin for High-Risk Myeloproliferative Disorders and AML Out of Myeloproliferative Disorders [NCT00588991]Phase 112 participants (Actual)Interventional2007-11-28Active, not recruiting
Phase I/II Study in Patients With Small Cell Lung Cancer (SCLC) of Veliparib in Combination With Topotecan [NCT03227016]Phase 130 participants (Anticipated)Interventional2016-10-31Recruiting
A Randomized, Double-Blind, Phase 2, Dose-Ranging Study to Evaluate the Safety and Efficacy of Veliparib and Whole Brain Radiation Therapy Versus Placebo and Whole Brain Radiation Therapy in Subjects With Brain Metastases From Non-Small Cell Lung Cancer [NCT01657799]Phase 2307 participants (Actual)Interventional2012-10-19Completed
A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-S [NCT02264990]Phase 3595 participants (Actual)Interventional2014-09-30Completed
Expanded Access Protocol With ABT-888 (Veliparib) in Patients With Metastatic BRCA-Mutation Associated or Triple Negative Breast Cancer [NCT02985658]0 participants Expanded AccessNo longer available
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00804908 (8) [back to overview]6-month Progression-Free Survival Rate
NCT00804908 (8) [back to overview]12-Month Overall Survival (OS) Rate
NCT00804908 (8) [back to overview]Disease Control Rate
NCT00804908 (8) [back to overview]Objective Response Rate
NCT00804908 (8) [back to overview]Overall Survival (OS): Time to Event
NCT00804908 (8) [back to overview]Progression-Free Survival (PFS): Time to Event
NCT00804908 (8) [back to overview]Time to Disease Progression
NCT00804908 (8) [back to overview]Time to Neurological/Brain Metastases Progression
NCT01012817 (2) [back to overview]Maximum Tolerated Dose of Topotecan Hydrochloride and Veliparib, Determined According to Incidence of Dose-limiting Toxicity, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
NCT01012817 (2) [back to overview]Percent of Patients With Tumor Response, Defined as Complete Response or Partial Response as Assessed Using Response Evaluation Criteria In Solid Tumors
NCT01026493 (4) [back to overview]Phase II: Overall Survival (OS)
NCT01026493 (4) [back to overview]Phase 1: Maximum Tolerated Dose (MTD)
NCT01026493 (4) [back to overview]Phase II: 6-month Progression-free Survival (PFS) Rate for Patients With Measurable Disease After Surgery
NCT01026493 (4) [back to overview]Phase II: Objective Response (Partial and Complete Response) Rate for Patients With Measurable Disease After Surgery
NCT01051596 (4) [back to overview]Percent of Patients With Disease Control
NCT01051596 (4) [back to overview]Percent of Patients With an Objective Response
NCT01051596 (4) [back to overview]Overall Survival
NCT01051596 (4) [back to overview]Median Progression-free Survival Time
NCT01205828 (4) [back to overview]Number of Participants Who Had Grade 3 or 4 Adverse Events
NCT01205828 (4) [back to overview]Overall Survival
NCT01205828 (4) [back to overview]Progression Free Survival
NCT01205828 (4) [back to overview]Clinical Benefit Rate
NCT01266447 (6) [back to overview]Progression-free Survival
NCT01266447 (6) [back to overview]Number of Patients With Dose-limiting Toxicities (in Safety lead-in)
NCT01266447 (6) [back to overview]Adverse Events (Grade 3 or Higher) During Treatment Period
NCT01266447 (6) [back to overview]Tumor Response
NCT01266447 (6) [back to overview]Overall Survival
NCT01266447 (6) [back to overview]Duration of Objective Response
NCT01306032 (6) [back to overview]Progression Free Survival
NCT01306032 (6) [back to overview]Percentage of Participants With an Overall Response Rate
NCT01306032 (6) [back to overview]Change in Poly-ADP Ribose (PAR) Concentration Levels From Baseline
NCT01306032 (6) [back to overview]Change in ϓH2AX- Positive Circulating Tumor Cells (CTCs) in Whole Blood
NCT01306032 (6) [back to overview]Number of Participants With Adverse Events
NCT01306032 (6) [back to overview]Number of Participants With Deleterious Mutations in DNA Repair Genes
NCT01326702 (7) [back to overview]Pharmacokinetic Parameters of Veliparib (Phase Ib)
NCT01326702 (7) [back to overview]Response Rate
NCT01326702 (7) [back to overview]Complete Response (CR) to Study Treatment (Phase IIa)
NCT01326702 (7) [back to overview]Progression-free Survival Using RECIST Version 1.1 (Phase IIa)
NCT01326702 (7) [back to overview]Maximum Tolerated Dose of Veliparib When Combined With Bendamustine Hydrochloride
NCT01326702 (7) [back to overview]Number of Participants With Adverse Events
NCT01326702 (7) [back to overview]Participants With Dose Limiting Toxicities
NCT01386385 (5) [back to overview]Maximum Tolerated Dose of Veliparib When Given Concurrently With Standard Carboplatin/Paclitaxel and Radiotherapy, Determined According to Incidence of Dose Limiting Toxicity (DLT) (Phase I)
NCT01386385 (5) [back to overview]Incidence of Serious (>= Grade 3) Adverse Events as Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase II)
NCT01386385 (5) [back to overview]Objective Response Rate (Phase II)
NCT01386385 (5) [back to overview]Overall Survival (Phase II)
NCT01386385 (5) [back to overview]Progression-free Survival of Patients Treated With Chemoradiotherapy Plus Veliparib (Phase II)
NCT01506609 (5) [back to overview]Objective Response Rate (ORR)
NCT01506609 (5) [back to overview]Clinical Benefit Rate (CBR) at Week 18
NCT01506609 (5) [back to overview]Overall Survival (OS)
NCT01506609 (5) [back to overview]Progression-Free Survival (PFS)
NCT01506609 (5) [back to overview]Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score
NCT01514201 (14) [back to overview]Percentage of Participants With Significant Changes in Poly(ADP-ribose) Polymerase (PARP) Levels Post-Veliparib, as Measured in Peripheral Blood Monocytes (PBMCs)
NCT01514201 (14) [back to overview]Progression-free Survival (PFS)
NCT01514201 (14) [back to overview]Trough for Veliparib [Pharmacokinetic Parameter]
NCT01514201 (14) [back to overview]Levels of Urinary Biomarkers
NCT01514201 (14) [back to overview]Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]
NCT01514201 (14) [back to overview]Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]
NCT01514201 (14) [back to overview]Percentage of Patients With Pseudo Progression
NCT01514201 (14) [back to overview]Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]
NCT01514201 (14) [back to overview]Maximum-tolerated Dose of Veliparib Defined as Highest Dose Level With Fewer Than 2 Dose Limiting Toxicities in 6 Patients as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)
NCT01514201 (14) [back to overview]Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]
NCT01514201 (14) [back to overview]Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)
NCT01514201 (14) [back to overview]Overall Survival
NCT01514201 (14) [back to overview]Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)
NCT01514201 (14) [back to overview]Terminal Half-life (t1/2) for Veliparib [Pharmacokinetic Parameter]
NCT01540565 (5) [back to overview]The Proportion of Patients Who Survive Progression-free for at Least 6 Months
NCT01540565 (5) [back to overview]Proportion of Patients With Complete and Partial Tumor Response
NCT01540565 (5) [back to overview]Duration of PFS
NCT01540565 (5) [back to overview]Duration of OS
NCT01540565 (5) [back to overview]Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0
NCT01576172 (5) [back to overview]Progression-free Survival (PFS)
NCT01576172 (5) [back to overview]Objective Response Rates in Patients With Measurable Disease.
NCT01576172 (5) [back to overview]Grade 4 or 5 Adverse Events
NCT01576172 (5) [back to overview]Confirmed Prostate-specific Antigen (PSA) Response Rate
NCT01576172 (5) [back to overview]Rates of PSA Decline
NCT01638546 (4) [back to overview]Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease
NCT01638546 (4) [back to overview]Overall Survival
NCT01638546 (4) [back to overview]Number of Participants With Adverse Events
NCT01638546 (4) [back to overview]Overall Response (ORR) by RECIST 1.1 Criteria
NCT01642251 (5) [back to overview]Progression Free Survival (Phase II)
NCT01642251 (5) [back to overview]Recommended Phase II Dose (Phase I)
NCT01642251 (5) [back to overview]Overall Survival (OS)
NCT01642251 (5) [back to overview]Neurotoxicity Total Score Change Between Baseline and 3 Months After Treatment Start
NCT01642251 (5) [back to overview]Overall Response Rate (ORR)
NCT01657799 (4) [back to overview]Best Tumor Response Rate
NCT01657799 (4) [back to overview]Overall Survival
NCT01657799 (4) [back to overview]Time to Clinical Brain Metastasis Progression
NCT01657799 (4) [back to overview]Time to Intracranial Progression (Radiographic)
NCT01711541 (2) [back to overview]Toxicity (Phase I and Phase II)
NCT01711541 (2) [back to overview]Dose Limiting Toxicity (Phase I)
NCT01818063 (1) [back to overview]Count of Participants That Achieve Pathologic Complete Response (PCR)
NCT01827384 (3) [back to overview]Number of Participants With an Objective Response
NCT01827384 (3) [back to overview]Proportion of Participants With 4 Month Progression-free Survival (PFS)
NCT01827384 (3) [back to overview]Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
NCT02152982 (5) [back to overview]Objective Tumor Response
NCT02152982 (5) [back to overview]Interaction With Optune Device
NCT02152982 (5) [back to overview]Progression-free Survival (PFS)
NCT02152982 (5) [back to overview]Overall Survival (OS)
NCT02152982 (5) [back to overview]Overall Adverse Event Rates for Grade 3 or Higher Adverse Events
NCT02163694 (1) [back to overview]Progression-Free Survival (PFS)
NCT02264990 (6) [back to overview]Progression Free Survival (PFS) in All Participants
NCT02264990 (6) [back to overview]Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
NCT02264990 (6) [back to overview]Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup
NCT02264990 (6) [back to overview]Objective Response Rate (ORR) in All Participants
NCT02264990 (6) [back to overview]Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup
NCT02264990 (6) [back to overview]Overall Survival in All Participants
NCT02289690 (20) [back to overview]Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
NCT02289690 (20) [back to overview]Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib
NCT02289690 (20) [back to overview]Phase 2: Objective Response Rate
NCT02289690 (20) [back to overview]Phase 2: Overall Survival
NCT02289690 (20) [back to overview]Phase 2: Progression-free Survival
NCT02289690 (20) [back to overview]Phase 1: Number of Participants With Adverse Events
NCT02289690 (20) [back to overview]Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib
NCT02305758 (3) [back to overview]Overall Survival (OS): Time to Event
NCT02305758 (3) [back to overview]Objective Response Rate (ORR)
NCT02305758 (3) [back to overview]Progression-Free Survival (PFS): Time to Event
NCT02412371 (5) [back to overview]Duration of Overall Response (DOR)
NCT02412371 (5) [back to overview]Progression-free Survival
NCT02412371 (5) [back to overview]Overall Survival
NCT02412371 (5) [back to overview]Objective Response Rate
NCT02412371 (5) [back to overview]Number of Participants With Dose-limiting Toxicities (DLTs)
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the BRCA-deficient Population
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the Intention-to-treat Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the ITT Population
NCT02723864 (4) [back to overview]Number of Participants With Worst Grade 2 or Higher Adverse Events Occurring in >5% of Participants at Least Possibly Related to Study Drugs
NCT02723864 (4) [back to overview]Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment
NCT02723864 (4) [back to overview]Number of Participants With a Best Response to the Antitumor Activity of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin
NCT02723864 (4) [back to overview]Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
NCT02890355 (6) [back to overview]Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
NCT02890355 (6) [back to overview]Progression Free Survival (PFS)
NCT02890355 (6) [back to overview]Overall Survival (OS)
NCT02890355 (6) [back to overview]Overall Response Rate, ORR
NCT02890355 (6) [back to overview]Duration of Response (DoR)
NCT02890355 (6) [back to overview]Disease Control Rate
NCT02921256 (3) [back to overview]Rate of Sphincter Preservation
NCT02921256 (3) [back to overview]Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0
NCT02921256 (3) [back to overview]Neoadjuvant Rectal Cancer (NAR) Score
NCT03061188 (6) [back to overview]ORR (Overall Response Rate)
NCT03061188 (6) [back to overview]Clinical Benefit Rate (CBR)
NCT03061188 (6) [back to overview]Overall Survival (OS)
NCT03061188 (6) [back to overview]Number of Patients Alive and Progression Free at 24 Weeks
NCT03061188 (6) [back to overview]Maximum Tolerated Dose (MTD)
NCT03061188 (6) [back to overview]Progression Free Survival (PFS)

6-month Progression-Free Survival Rate

The 6-month progression-free survival rate was defined as the percentage of participants without disease progression at 6 months.The distribution of 6-month progression-free survival rate, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Interventionpercentage of participants (Number)
Placebo for ABT-888 BID + TMZ QD19.1
ABT-888 20 mg BID + TMZ QD32.8
ABT-888 40 mg BID + TMZ QD30.7

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12-Month Overall Survival (OS) Rate

The 12-month overall survival rate was defined as the percentage of participants surviving at 12 months. The distribution of 12-month OS rate was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Per protocol, survival was to be assessed every 4 weeks or as needed after participant is registered as off-study for up to 18 months. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

Interventionpercentage of participants (Number)
Placebo for ABT-888 BID + TMZ QD52.6
ABT-888 20 mg BID + TMZ QD43.5
ABT-888 40 mg BID + TMZ QD54.1

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Disease Control Rate

The disease control rate was defined as the percentage of participants who had at least stable disease (complete response, partial response, or stable disease) through the end of Week 8. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Placebo for ABT-888 BID + TMZ QD48.7
ABT-888 20 mg BID + TMZ QD62.9
ABT-888 40 mg BID + TMZ QD59.1

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Objective Response Rate

The objective response rate was defined as the percentage of participants with a confirmed CR or PR per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by computed tomography (CT) scan: complete response (CR), disappearance of all target lesions; partial response (PR), ≥30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

Interventionpercentage of participants (Number)
Placebo for ABT-888 BID + TMZ QD7.0
ABT-888 20 mg BID + TMZ QD10.3
ABT-888 40 mg BID + TMZ QD9.6

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Overall Survival (OS): Time to Event

OS was defined as the number of days from the date the participant was randomized to the date of death. All deaths were included, whether the participant was still taking or had discontinued study drug. If a participant had not died and was lost to follow-up, then data were censored at the last study visit or contact date, or date the participant was last known to be alive, whichever was later; if the participant was not lost to follow-up, then data were censored at the last study visit or contact date, whichever was later. The distribution of OS was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the OS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints. (NCT00804908)
Timeframe: Per protocol, survival follow-up information was to be obtained every 3 months for up to 18 months after the final visit for the subject. The maximum observed follow-up at the overall survival analysis time was 21.0 months.

,,
Interventiondays (Number)
25th Percentile50th percentile75th percentile
ABT-888 20 mg BID + TMZ QD204327NA
ABT-888 40 mg BID + TMZ QD181412NA
Placebo for ABT-888 BID + TMZ QD207390559

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Progression-Free Survival (PFS): Time to Event

PFS: the number of days from the date that the participant was randomized to the date the participant experienced a confirmed event of disease progression (radiological, as determined by the central imaging center; or clinical, as determined by the investigator), or to the date of death (all causes of mortality) if disease progression was not reached. All events were included whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced a confirmed event of disease progression, provided the death occurred within 8 weeks of the last available disease progression assessment. The distribution of PFS, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the quartiles for the PFS distribution are provided. (NCT00804908)
Timeframe: Every Cycle (28 Days) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

,,
Interventiondays (Number)
25th Percentile50th Percentile75th Percentile
ABT-888 20 mg BID + TMZ QD56113225
ABT-888 40 mg BID + TMZ QD53110226
Placebo for ABT-888 BID + TMZ QD5460163

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Time to Disease Progression

The distribution of time to disease progression, as determined by the central imaging center (radiological)/ investigator (clinical), was estimated for each treatment group using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the PFS distribution are provided. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ treatment groups were statistically significantly better than the Placebo + TMZ treatment group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Every Cycle (28 Days), until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

,,
Interventiondays (Number)
25th Percentile50th percentile75th percentile
ABT-888 20 mg BID + TMZ QD56113225
ABT-888 40 mg BID + TMZ QD53110226
Placebo for ABT-888 BID + TMZ QD5460163

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Time to Neurological/Brain Metastases Progression

Time to neurological/brain metastases progression, defined as the number of days from the date of randomization to the date the participant experienced an event of neurological/brain metastases progression, was estimated using Kaplan-Meier methodology. Point estimates and 95% CIs for the quartiles for the distribution are provided. All events of progression were included, regardless of whether the event occurred while the participant was still taking study drug. If a participant did not experience an event, data were censored at the date of the last available brain CT scan. For participants with no postbaseline brain CT scans, data were censored at randomization. Per protocol, because neither the ABT-888 20 mg BID + TMZ nor ABT-888 40 mg BID + TMZ groups were statistically significantly better than the Placebo + TMZ group for the primary endpoint of PFS, confirmatory statistical testing was not continued for any secondary endpoints, regardless of the observed P values. (NCT00804908)
Timeframe: Every 2 cycles (8 weeks) until disease progression was observed or another reason for discontinuation of assessments was identified by the investigator. The maximum observed followup duration at the progression-free survival analysis time was 9.7 months.

,,
Interventiondays (Number)
25th Percentile50th percentile75th percentile
ABT-888 20 mg BID + TMZ QD119NANA
ABT-888 40 mg BID + TMZ QD184184NA
Placebo for ABT-888 BID + TMZ QD60NANA

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Maximum Tolerated Dose of Topotecan Hydrochloride and Veliparib, Determined According to Incidence of Dose-limiting Toxicity, Graded Using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

The number of patients with a dose limiting toxicity will be reported. Dose-limiting toxicity (DLT) will be defined as a cycle 1 adverse event attributed (definitely, probably, or possibly) to the study treatment and meeting the following criteria: Grade 4 anemia, grade 4 neutrophil count decrease, grade 4 platelet count decrease, Serum creatinine >= 2 times baseline or ≥ 2 times the upper limit of normal if baseline is < the upper limit of normal, or other >= Grade 3 as per NCI Common Terminology Criteria for Adverse Events CTCAE version 4.0. >= Grade 3 nausea, vomiting, or diarrhea with maximal supportive treatment(s) will be considered dose-limiting. Grade 3 fatigue or anorexia will not be considered dos (NCT01012817)
Timeframe: 4 weeks

InterventionParticipants (Count of Participants)
Phase 1 Dose Level 10
Phase 1 Dose Level 20
Phase 1 Dose Level 30
Phase 1 Dose Level 40
Phase 1 Dose Level 53
Phase 1 Dose Level 62
Phase 1 Dose Level 70
Phase 1 Dose Level 80
Phase 1 Dose Level 90
Phase 1 Dose Level 101
Phase 1 Dose Level 110
Phase 1 Dose Level 121
Phase 1 Dose Level 132

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Percent of Patients With Tumor Response, Defined as Complete Response or Partial Response as Assessed Using Response Evaluation Criteria In Solid Tumors

The proportion of successes will be estimated by the number of successes(CR or PR) divided by the total number of evaluable patients. Confidence intervals for the true success proportion will be calculated according to the approach of Duffy and Santner (1987). Complete Response (CR) is defined as disappearance of all target lesions and, if non target lesions exist, the disappearance of all non-target lesions and normalization of tumor maker level. At least 30% decrease in the sum of the longest diameter (LD) of target lesion taking as reference the baseline sum. (NCT01012817)
Timeframe: Up to 48 weeks (12 courses)

Interventionpercent of patients with response (Number)
Phase 1 Dose Level 10
Phase 1 Dose Level 233
Phase 1 Dose Level 30
Phase 1 Dose Level 40
Phase 1 Dose Level 517
Phase 1 Dose Level 60
Phase 1 Dose Level 70
Phase 1 Dose Level 80
Phase 1 Dose Level 90
Phase 1 Dose Level 100
Phase 1 Dose Level 110
Phase 1 Dose Level 1250
Phase 1 Dose Level 130
Phase 20

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Phase II: Overall Survival (OS)

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 6 months. (NCT01026493)
Timeframe: Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.)

Interventionmonths (Median)
Phase II: Arm 1/BEV-NAIVE10.3
Phase II: Arm 2/BEV-NAIVE10.7
Phase II: Arm 1/BEV-FAILURE4.7
Phase II: Arm 2/BEV-FAILURE4.7

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Phase 1: Maximum Tolerated Dose (MTD)

Dose limiting toxicity (DLT) = any of the following events within 1st 8 weeks of treatment attributable to study drugs: Any grade (gr) 3/4 thrombocytopenia, gr 4 anemia, gr 3 neutropenia with fever (>100.4). gr 4 neutropenia lasting > 7 days; Any non-hematologic (NH) gr 3+ toxicity (TOX), excluding alopecia, despite maximal medical therapy (MLT); NH TOX such as rash, nausea, vomiting, diarrhea, mucositis, hypophosphatemia, and hypertension will only be considered DLTs if they remain gr 3+ despite MLT; 2nd occurrence of thromboembolism; Failure to recover from TOX (<= gr 1) to be eligible for re-treatment with study drugs <= 14 days of last dose of either drug; Any episode of non-infectious radiologically observed pneumonitis gr 2-4 any duration. Dose level will be considered acceptable if <= 1 of the 1st 6 eligible patients experiences a DLT. If current level is considered acceptable, dose escalation occurs. Otherwise preceding acceptable dose level will be declared the MTD. (NCT01026493)
Timeframe: Start of treatment to 8 weeks.

Interventionparticipants (Number)
Phase I: Dose Level 11
Phase I: Dose Level 2a0
Phase I: Dose Level 2b1
Phase I: Dose Level 31

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Phase II: 6-month Progression-free Survival (PFS) Rate for Patients With Measurable Disease After Surgery

For patients with measureable disease after surgery: Progression defined as ≥ 25% increase in size of enhancing tumor or any new tumor; or neurologically worse, and steroids stable/increased. Bevacizumab (BEV)-naïve group: p0= 15% as estimate of 6-mo. PFS [null hypothesis (NH)], p1= 30%, with a 15% absolute increase [alternative hypothesis (AH)]. Error rates of 10% alpha and 10% beta. If <= 11 patients experience 6-month PFS of the first 53 analyzable patients, then do not reject the null hypothesis that the 6-month PFS rate of experimental arm is less than 15%; BEV-failure group: p0 = 2% as a conservative estimate of 6-month PFS [NH], p1 = 15%, with a 13% absolute increase [AH]. Using first 26 analyzable subjects for each experimental arm, there is >= 90% power to detect >= 15% increase at a significance level of 0.10, using a 1-sided binomial test. If >= 2 patients (8%) are progression free at 6 mo., then claim this regimen to be promising in the patient group. (NCT01026493)
Timeframe: Randomization to 6 months.

Interventionparticipants (Number)
Phase II: Arm 1/BEV-NAIVE9
Phase II: Arm 2/BEV-NAIVE9
Phase II: Arm 1/BEV-FAILURE1
Phase II: Arm 2/BEV-FAILURE1

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Phase II: Objective Response (Partial and Complete Response) Rate for Patients With Measurable Disease After Surgery

Response and progression will be evaluated using standard criteria for patients with malignant gliomas (Macdonald 1990). Partial response and complete response are centrally reviewed. (NCT01026493)
Timeframe: Analysis occurs after all patients have been on study for at 6 months. (Patients are followed from randomization to death or study termination whichever occurs first.)

Interventionpercentage of participants (Number)
Phase II: Arm 1/BEV-NAIVE0
Phase II: Arm 2/BEV-NAIVE3.8
Phase II: Arm 1/BEV-FAILURE5.3
Phase II: Arm 2/BEV-FAILURE0

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Percent of Patients With Disease Control

Disease control rate defined as stable disease, partial response, or complete response according to the Response Evaluation Criteria in Solid Tumors (RECIST). (NCT01051596)
Timeframe: 2 months

InterventionParticipants (Count of Participants)
ABT-888 and Temozolomide18

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Percent of Patients With an Objective Response

Objective response rate defined as partial response or complete response according to RECIST criteria (NCT01051596)
Timeframe: 2 months

InterventionParticipants (Count of Participants)
ABT-888 and Temozolomide2

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Overall Survival

Overall survival defined as the time in days from study entry until death (NCT01051596)
Timeframe: 1 year

InterventionMonths (Median)
ABT-888 and Temozolomide6.6

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Median Progression-free Survival Time

Progression-free survival defines as the time in days from study study entry until progression or death (NCT01051596)
Timeframe: 1 year

InterventionMonths (Median)
ABT-888 and Temozolomide1.8

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Number of Participants Who Had Grade 3 or 4 Adverse Events

Record of all toxicities graded according to the NCI CTCAE version 3.0 (NCT01205828)
Timeframe: 6 months

Interventionparticipants (Number)
ABT-888 and Temozolomide5

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Overall Survival

the number of months between a patient's enrollment and his/her date of death (NCT01205828)
Timeframe: 2 years

Interventionmonths (Median)
ABT-888 and Temozolomide13.1

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Progression Free Survival

The number of months between a patient's enrollment and his/her disease progression (NCT01205828)
Timeframe: 2 years

Interventionmonths (Median)
ABT-888 and Temozolomide1.9

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Clinical Benefit Rate

complete response at any time + partial response at any time + stable disease after 8 weeks of treatment based on RECIST Criteria (NCT01205828)
Timeframe: 8 weeks

Interventionparticipants (Number)
ABT-888 and Temozolomide3

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Progression-free Survival

Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is defined as at least a 20% increase in the sum of the longest dimensions (LD) of target lesions taking as reference the smallest sum LD recorded since study entry, or unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions, or global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or death due to disease without prior objective documentation of progression. (NCT01266447)
Timeframe: From study entry to disease progression, death or date of last contact, whichever occurs first, up to 5 years of follow-up.

Interventionmonths (Median)
ABT-888, Topotecan and Filgrastim or Pegfilgrastim2.0

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Number of Patients With Dose-limiting Toxicities (in Safety lead-in)

A dose-limiting toxicity (DLT) is assessed by NCI CTCAE v4, occurring during cycle 1 of therapy.: A dose-limiting toxicity (DLT) is defined as either hematologic or non-hematologic toxicity assessed by NCI CTCAE v4, occurring during cycle 1 of therapy, which cause any of the following: For hematologic toxicity - dose delay of greater than 2 weeks due to failure to recover counts, Treatment related febrile neutropenia, grade 4 neutropenia lasting >7 days, treatment related grade 4 thrombocytopenia or clinically significant bleeding with grade 3 thrombocytopenia. For non-hematologic toxicity; study treatment related grade 3 or 4 non-hematological toxicity (excluding anorexia, constipation, fatigue, hypersensitivity/allergic reaction to one of the study drugs, nausea & vomiting, and grade 3 dehydration), grade 4 nausea and vomiting for >48 hours despite maximum medical management, electrolyte imbalance of > or equal to grade 3 that can be replaced within 48 hours; any drug related death (NCT01266447)
Timeframe: Up to 21 days

Interventionparticipants (Number)
ABT-888, Topotecan and Filgrastim or Pegfilgrastim1

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Adverse Events (Grade 3 or Higher) During Treatment Period

Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0. (NCT01266447)
Timeframe: During treatment period and up to 30 days after stopping the study treatment.The average of study treatment time was 2.3 months.

InterventionParticipants (Number)
LeukopeniaThrombocytopeniaNeutropeniaAnemiaOther InvestigationsCardiac DisordersGastrointestinal DisordersGeneral Disorders & administration site conditionsInfections and InfestationsMetabolism and nutrition disordersMusculoskeletal and connective tissue disordersNeoplasms benign, malignant and unspecifiedNervous system disordersRenal and urinary disordersReproductive system and breast disordersRespiratory, thoracic and mediastinal disordersSurgical and medical proceduresVascular disorders
ABT-888, Topotecan and Filgrastim or Pegfilgrastim61251641754351102413

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Tumor Response

Complete and Partial Tumor Response as Assessed by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation. (NCT01266447)
Timeframe: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicted based on symptoms or physical signs suggestive of progressive disease. The average time was 2.3 months

Interventionpercentage of participants (Number)
ABT-888, Topotecan and Filgrastim or Pegfilgrastim7.4

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Overall Survival

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. (NCT01266447)
Timeframe: From study entry to death or last contact, up to 5 years of follow-up.

Interventionmonths (Median)
ABT-888, Topotecan and Filgrastim or Pegfilgrastim8.2

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Duration of Objective Response

Duration of objective response is defined as the duration from the time measurement criteria is met for partial or complete response by RECIST 1.1, whichever is first recorded, until the first date the recurrent or progressive disease is objectively documented. Per Response Evaluation Criteria in Solid Tumors (RECIST) criteria Complete Response (CR), disappearance of all target and non-target lesions without evidence of new lesion; Partial Response (PR), at least 30% decrease in the sum of the longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD with no unequivocal progression of non-target lesions and no evidence of new lesion. Complete or partial response requires confirmation at greater than or equal to 4 weeks from initial documentation. (NCT01266447)
Timeframe: Every other cycle for first 6 months; then every 3 months until disease progression confirmed; and at any other time if clinically indicated based on symptoms or signs suggestive of progressive disease.The average of study treatment time was 2.3 months.

InterventionMonths (Median)
ABT-888, Topotecan and Filgrastim or Pegfilgrastim5.3

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Progression Free Survival

Time to progression for each participant for the initial intervention. (NCT01306032)
Timeframe: Ovarian cancer patients stayed on study for an average of 126 days and triple-negative breast cancer patients for an average of 71 days.

InterventionCycles of therapy (Median)
Triple-negative Breast Cancer: ABT-888 + Cyclophosphamide3
Triple-negative Breast Cancer: Cyclophosphamide Alone2
BRCA-positive Ovarian Cancer: ABT-888 + Cyclophosphamide3
BRCA-positive Ovarian Cancer: Cyclophosphamide Alone3

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Percentage of Participants With an Overall Response Rate

Complete response (CR) + partial response (PR)) of the combination of ABT-888 with metronomic oral cyclophosphamide to the response rate (CR+PR) of metronomic oral cyclophosphamide in patients with deleterious BRCA mutations and refractory ovarian cancer or patients with primary peritoneal or ovarian high-grade serous carcinoma or fallopian tube cancer. CR + PR was determined by the Response Evaluation Criteria in Solid Tumors (RECIST). CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm). Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (NCT01306032)
Timeframe: an average of 126 days for ovarian; 71 days for TNBC; for crossover intervention, pts stayed on study for an avg of 134 days for ovarian; 50 days for TNBC.

Interventionpercentage of participants (Number)
Triple-negative Breast Cancer: ABT-888 + Cyclophosphamide9.5
Triple-negative Breast Cancer: Cyclophosphamide Alone5.6
Triple-negative Breast Cancer: Crossover0
BRCA-positive Ovarian Cancer: ABT-888 + Cyclophosphamide11.8
BRCA-positive Ovarian Cancer: Cyclophosphamide Alone19.4
BRCA-positive Ovarian Cancer: Crossover3.4

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Change in Poly-ADP Ribose (PAR) Concentration Levels From Baseline

PAR levels (in pg/μg protein) were assessed in peripheral blood mononuclear cells (PBMCs) by immunoassay to assess poly (ADP-ribose) polymerase (PARP) activity. Significant inhibition of PARP activity is associated with 50% or greater reduction in PAR levels. (NCT01306032)
Timeframe: At baseline (t=0h) and 4h post drug administration (t=4h)

Interventionpg/μg protein (Mean)
BRCA-positive Ovarian Cancer: ABT-888 & Cyclophosphamide-81
BRCA-positive Ovarian Cancer: Crossover-88
Triple-negative Breast Cancer: Cyclophosphamide & ABT-888-74
Triple-negative Breast Cancer: Crossover-85

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Change in ϓH2AX- Positive Circulating Tumor Cells (CTCs) in Whole Blood

Number of CTCs (evaluable defined as ≥ 6 CTCs) were measured in whole blood during the course of treatment to determine drug-induced deoxyribonucleic acid damage in tumor cells. (NCT01306032)
Timeframe: At baseline (t=0h) and 24h post drug administration (t=24h)

InterventionϓH2AX- Positive CTCs (Mean)
BRCA-positive Ovarian Cancer: Crossover400
Triple-negative Breast Cancer: Cyclophosphamide & ABT-888200
Triple-negative Breast Cancer: Crossover9.5

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Number of Participants With Adverse Events

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. (NCT01306032)
Timeframe: up to 30 days following the last dose of study drug.

InterventionParticipants (Count of Participants)
BRCA-positive Ovarian Cancer: ABT-888 & Cyclophosphamide28
BRCA-positive Ovarian Cancer: Cyclophosphamide Alone24
BRCA-positive Ovarian Cancer: Crossover29
Triple-negative Breast Cancer: Cyclophosphamide & ABT-88814
Triple-negative Breast Cancer: Cyclophosphamide Alone4
Triple-negative Breast Cancer: Crossover6
Non-Hodgkin's: ABT-888 & Cyclophosphamide0
Non-Hodgkin's: Cyclophosphamide Alone1

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Number of Participants With Deleterious Mutations in DNA Repair Genes

Gene expression profiling was performed in archival tumor tissue for a panel of 211 genes using deoxyribonucleic acid (DNA) array to determine deleterious mutations (i.e. nonsynonymous mutations at coding regions) of genes. Sequences were mapped to human genome reference hg19. Variants were identified with VarScan, annotated with AVIA, and masked to the exonic or exonic:splicing regions of the 211 interrogated DNA repair genes, with nonsynonymous/frameshift/stop-gain/stop-loss variants that have a population frequency of 1% or less in either 1000G (2014_04) or the ExomeSequencingProject (ESP6500si_all) with a minimum variant frequency of 10% and at least 20 reads. Lastly, variants were manually inspected for known platform and mapping errors. (NCT01306032)
Timeframe: Optional tumor biopsies were performed prior to start of treatment (baseline) and 6 months

InterventionParticipants (Count of Participants)
BRCA-positive Ovarian Cancer: ABT-888 & Cyclophosphamide28
BRCA-positive Ovarian Cancer: Crossover27

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Pharmacokinetic Parameters of Veliparib (Phase Ib)

Area Under the Curve from time zero to 12 hours following Veliparib administration (NCT01326702)
Timeframe: From time zero to 12 hours on day 2 of course 1

Interventionμg*h/mL (Geometric Mean)
Dose Level 1-Bendamustine 70 mg/m2, ABT-888 50 mg1.79
Dose Level 2: Bendamustine 90 mg/m2, ABT-888 50 mg3.58
Dose Level 3: Bendamustine 90 mg/m2, ABT-888 100 mg BID7.93
Dose Level 4: Bendamustine 90 mg/m2, ABT-888 150 mg BID12.6
Dose Level 5: Bendamustine 90 mg/m2, ABT-888 200 mg BID16.9
Dose Level 6: Bendamustine 90 mg/m2, ABT-888 300 mg BID19.0
Dose Level 7: Bendamustine 90 mg/m2, ABT-888 400 mg BID25.0

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Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions. (NCT01326702)
Timeframe: 2 years

,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable DiseaseProgression of Disease
Dose Level 1-Bendamustine 70 mg/m2, ABT-888 50 mg0111
Dose Level 2: Bendamustine 90 mg/m2, ABT-888 50 mg0120
Dose Level 3: Bendamustine 90 mg/m2, ABT-888 100 mg BID1022
Dose Level 4: Bendamustine 90 mg/m2, ABT-888 150 mg BID0020
Dose Level 5: Bendamustine 90 mg/m2, ABT-888 200 mg BID0102
Dose Level 6: Bendamustine 90 mg/m2, ABT-888 300 mg BID4451
Dose Level 7: Bendamustine 90 mg/m2, ABT-888 400 mg BID0002

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Complete Response (CR) to Study Treatment (Phase IIa)

Summary statistics will be used for CR. Responses will be evaluated by the International Uniform Response Criteria for Multiple Myeloma. (NCT01326702)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
All Study Participants5

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Progression-free Survival Using RECIST Version 1.1 (Phase IIa)

Kaplan-Meier estimates will be calculated and log-rank tests will be employed when certain comparisons are needed. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the RECIST criteria. (NCT01326702)
Timeframe: 2 years

InterventionMonths (Median)
All Study Participants14.2

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Maximum Tolerated Dose of Veliparib When Combined With Bendamustine Hydrochloride

Maximum Tolerated Dose (MTD) reflects the highest dose of Veliparib when combined with Bendamustine Hydrochloride that did not cause a DLT. The maximum tolerated dose (MTD) was defined as the highest dose level at which 33% of patients experienced DLT. (NCT01326702)
Timeframe: 28 days

Interventionmg (Number)
All Study Participants300

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Number of Participants With Adverse Events

Adverse events assessed by NCI CTCAE version 4.0 (Phase Ib) See adverse events section. (NCT01326702)
Timeframe: 2 years

Interventionparticipants (Number)
Dose Level 1-Bendamustine 70 mg/m2, ABT-888 50 mg3
Dose Level 2: Bendamustine 90 mg/m2, ABT-888 50 mg3
Dose Level 3: Bendamustine 90 mg/m2, ABT-888 100 mg BID4
Dose Level 4: Bendamustine 90 mg/m2, ABT-888 150 mg BID2
Dose Level 5: Bendamustine 90 mg/m2, ABT-888 200 mg BID2
Dose Level 6: Bendamustine 90 mg/m2, ABT-888 300 mg BID5
Dose Level 7: Bendamustine 90 mg/m2, ABT-888 400 mg BID3

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Participants With Dose Limiting Toxicities

(NCT01326702)
Timeframe: 28 days

Interventionparticipants (Number)
Dose Level 1-Bendamustine 70 mg/m2, ABT-888 50 mg0
Dose Level 2: Bendamustine 90 mg/m2, ABT-888 50 mg0
Dose Level 3: Bendamustine 90 mg/m2, ABT-888 100 mg BID1
Dose Level 4: Bendamustine 90 mg/m2, ABT-888 150 mg BID0
Dose Level 5: Bendamustine 90 mg/m2, ABT-888 200 mg BID0
Dose Level 6: Bendamustine 90 mg/m2, ABT-888 300 mg BID1
Dose Level 7: Bendamustine 90 mg/m2, ABT-888 400 mg BID2

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Maximum Tolerated Dose of Veliparib When Given Concurrently With Standard Carboplatin/Paclitaxel and Radiotherapy, Determined According to Incidence of Dose Limiting Toxicity (DLT) (Phase I)

"DLTs will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. DLTs must be attributable (probably, possibly, definitely related) to the study regimen and only occur during RT or 2 weeks after completing RT.~DLTs are defined as:~Radiation esophagitis or dermatitis radiation Grade 3 that lasts > 7 consecutive days or Grade 4~Grade 4 neutropenia for > 7 days or neutropenic fever ( ANC <500 and temperature >= 38.5 oC)~Grade 4 thrombocytopenia~Grade 4 nausea/vomiting despite appropriate antiemetic therapy~Delays in radiotherapy or chemotherapy or ABT-888 due to toxicity of > 3 weeks~All other non-hematologic toxicities >= Grade 3, except~anorexia~fatigue~infection without neutropenia~Grade 3 AST/ALT elevations <= 7 days, infusion reactions~Grade 3 or 4 lymphopenia~Grade 3 or 4 electrolyte abnormalities that are corrected to <=Grade 2 in < 48 hours~Grade 3 dehydration lasting < 7 days" (NCT01386385)
Timeframe: 9 weeks

Interventiondose limiting toxicity (Number)
Phase I 40mg Veliparib1
Phase I 80mg Veliparib1
Phase I 120mg Veliparib0

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Incidence of Serious (>= Grade 3) Adverse Events as Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase II)

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT01386385)
Timeframe: Duration of treatment and follow up until death or 5 years post registration

,,,
InterventionParticipants (Number)
AnemiaAnorexiaDehydrationDiarrheaDysphagiaEsophageal painEsophagitisFatigueHyperglycemiaHypocalcemiaHypoglycemiaHypokalemiaHypomagnesemiaHyponatremiaHypotensionLung infectionLymphocyte count decreasedMucositis oralNauseaNeutrophil count decreasedPlatelet count decreasedPneumonitisUpper gastrointestinal hemorrhageVomitingWeight lossWhite blood cell decreased
Arm I Concurrent Chemoradiation (Veliparib, 3D-CRT, Carboplati11000111100000103103100012
Arm I Consolidation (Veliparib, Carboplatin, Paclitaxel)11112001000000002013101102
Arm II Concurrent Chemoradiation (Placebo, 3D-CRT, Carboplatin01100011011113014001010102
Arm II Consolidation (Placebo, Carboplatin, Paclitaxel)00000000100110002000010010

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Objective Response Rate (Phase II)

ORR is defined as the percentage of participants with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (NCT01386385)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)56
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)69

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Overall Survival (Phase II)

From date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. (NCT01386385)
Timeframe: Up to 5 years

Interventionmonths (Median)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)27.6
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)15.2

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Progression-free Survival of Patients Treated With Chemoradiotherapy Plus Veliparib (Phase II)

"Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive are censored at date of last contact.~Assessed by Response Evaluation Criteria in Solid Tumors, RECIST 1.1" (NCT01386385)
Timeframe: The time from randomization to progression or death due to any cause, assessed up to 5 years

Interventionmonths (Median)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)9.3
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)9.9

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Objective Response Rate (ORR)

The objective response rate, defined as percentage of participants with a confirmed CR or PR based on RECIST 1.1 criteria. CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 0 mm. PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline SODs. (NCT01506609)
Timeframe: Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for ORR was 34 months.

Interventionpercentage of participants (Number)
Group 2 Placebo + Carboplatin/Paclitaxel61.3
Group 2 Veliparib + Carboplatin/Paclitaxel77.8
Group 2 Veliparib + TMZ28.6

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Clinical Benefit Rate (CBR) at Week 18

"CBR: percentage of participants who were progression-free at 18 weeks, defined as complete response (CR), partial response (PR), stable disease (SD) or non-CR/non-disease progression (PD) per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1.~CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 0 mm. PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (SOD). PD: >= 20% increase in the SOD of target lesions, taking as reference the smallest SOD recorded since the treatment started (baseline or after) or the appearance of >=1 new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after)." (NCT01506609)
Timeframe: Week 18

Interventionpercentage of participants (Number)
Group 2 Placebo + Carboplatin/Paclitaxel87.0
Group 2 Veliparib + Carboplatin/Paclitaxel90.7
Group 2 Veliparib + TMZ73.0

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Overall Survival (OS)

Time to death for a given participant was defined as the number of months from the day the participant is randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurs while the participant was still taking study drug, or after the participant discontinued study drug. If a participant had not died, then the data will be censored at the date when the participant was last known to be alive. (NCT01506609)
Timeframe: From Cycle 1 Day 1 until participant's death or 3 years post discontinuation (data cutoff date: 04 March 2016); maximum duration of follow up for OS was 72 months.

Interventionmonths (Median)
Group 2 Placebo + Carboplatin/Paclitaxel25.4
Group 2 Veliparib + Carboplatin/Paclitaxel28.3
Group 2 Veliparib + TMZ19.1

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Progression-Free Survival (PFS)

PFS is defined as the number of months from the date the participant was randomized to the date of radiographic progression as determined by the central imaging center, or to the date of all cause deaths within 63 days of last tumor assessment if disease progression was not reached. (NCT01506609)
Timeframe: Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for PFS was 34 months.

Interventionmonths (Median)
Group 2 Placebo + Carboplatin/Paclitaxel12.3
Group 2 Veliparib + Carboplatin/Paclitaxel14.1
Group 2 Veliparib + TMZ7.4

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Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score

EORTC QLQ-CIPN20 sensory subscale score was calculated following the standard scoring algorithm, transformed to a 0 (low quality of life) to 100 (best quality of life) scale. A positive change from baseline indicates improvement. (NCT01506609)
Timeframe: Baseline, Week 18

Interventionscore on a scale (Mean)
Group 2 Placebo + Carboplatin/Paclitaxel13.94
Group 2 Veliparib + Carboplatin/Paclitaxel11.24

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Percentage of Participants With Significant Changes in Poly(ADP-ribose) Polymerase (PARP) Levels Post-Veliparib, as Measured in Peripheral Blood Monocytes (PBMCs)

Blood samples were collected from patients and assessed pre- and post-Veliparib to assess treatment-induced changes. A significant change in PBMC PARP level was arbitrarily defined as a >50% increase or decrease from the pre-treatment level, documented at week 6 and/or week 11 after starting protocol therapy. (NCT01514201)
Timeframe: Baseline and up to 11 weeks

Interventionpercentage of participants (Number)
Phase I, Dose Level 1 (50 mg)100
Phase I, Dose Level 2 (65 mg)100
Phase I, Dose Level 3 (85 mg)75
Phase II (MTD)36

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Progression-free Survival (PFS)

PFS was defined as the interval from date of treatment initiation to date of first event (disease progression or relapse, second malignancy or death from any cause). Patients who had not failed at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate PFS. A 3-year estimate with a 95% confidence interval is reported. (NCT01514201)
Timeframe: Time from initiation of treatment to the earliest date of failure (disease progression, death from any cause, or second malignancy), assessed up to 3 years

InterventionPercent probability (Number)
Phase II Patients + Phase I MTD Patients2.9

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Trough for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

Interventionng/mL (Mean)
Phase I, Dose Level 1 (50 mg)58
Phase I, Dose Level 2 (65 mg)140
Phase I, Dose Level 3 (85 mg)163
Phase II (MTD)84

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Levels of Urinary Biomarkers

Urine samples were analyzed for a panel of biomarkers. Netrin-1 levels were determined by ELISA. Levels of matrix metalloproteinase 3 (MMP3) and basic fibroblast growth factor (bFGF) were analyzed using custom Luminex® screening assays. Tissue inhibitor of metalloproteinase 1 (TIMP1) levels were analyzed using a Luminex® performance assay. Protein concentrations are given in picograms per microgram (pg/μg), and were determined by dividing the concentration of the target protein in the sample (pg/mL) by the concentration of total protein in the sample (μg/mL) as a normalization measure. (NCT01514201)
Timeframe: Baseline to up to 3 years

,,,
Interventionpg/μg (Median)
MMP3 at pre-studyMMP3 at week 10-11MMP3 at week 18MMP3 at week 26Netrin-1 at pre-studyNetrin-1 at week 10-11Netrin-1 at week 18Netrin-1 at week 26TIMP1 at pre-studyTIMP1 at week 10-11TIMP1 at week 18TIMP1 at week 26bFGF at pre-studybFGF at week 10-11bFGF at week 18bFGF at week 26
Phase I, Dose Level 1 (50 mg)2.01.44.32.90.10.10.30.43.46.210.77.33.13.610.37.7
Phase I, Dose Level 2 (65 mg)1.01.01.70.40.10.10.10.29.911.97.75.21.92.13.50.9
Phase I, Dose Level 3 (85 mg)0.00.80.71.00.10.10.00.010.812.314.832.81.21.81.31.1
Phase II (MTD)1.12.62.33.00.10.00.10.07.37.57.110.74.53.54.44.5

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Apparent Volume of Distribution (Vd/F) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

InterventionL/m^2 (Mean)
Phase I, Dose Level 1 (50 mg)75.4
Phase I, Dose Level 2 (65 mg)56.1
Phase I, Dose Level 3 (85 mg)63.9
Phase II (MTD)73.1

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Maximum Concentration of Veliparib (Cmax) on Days 1 and 4 (Measured in ng/mL) [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug. (NCT01514201)
Timeframe: Up to day 4

,,,
Interventionng/mL (Mean)
Day 1, Cmax (ng/mL)Day 4, Cmax (ng/mL)
Phase I, Dose Level 1 (50 mg)519409
Phase I, Dose Level 2 (65 mg)843788
Phase I, Dose Level 3 (85 mg)1074954
Phase II (MTD)844717

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Percentage of Patients With Pseudo Progression

For participants that showed possible tumor progression (pseudo progression) on magnetic resonance imaging (MRI) during the first 6 months of therapy, treating physicians had the option of allowing patients to remain on therapy and repeating the disease assessment in 4-6 weeks. If the repeat MRI at 4-6 weeks showed disease progression, the patient was noted to have true disease progression (and the progression date corresponded to that of the first MRI). If the repeat MRI at 4-6 weeks did not show disease progression, then the patient was noted to have pseudo progression. The percentage of patients observed to have experienced pseudo progression was provided with a 95% confidence interval. (NCT01514201)
Timeframe: Up to 6 months

InterventionPercentage of participants (Number)
Phase I, Dose Level 1 (50 mg)33.3
Phase I, Dose Level 2 (65 mg)16.7
Phase I, Dose Level 3 (85 mg)0
Phase II (MTD)12.8

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Maximum Concentration of Veliparib (Cmax) on Day 1 (Measured in μM) [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. Cmax measures the highest concentration of drug. (NCT01514201)
Timeframe: Day 1

InterventionμM (Mean)
Phase I, Dose Level 1 (50 mg)2.12
Phase I, Dose Level 2 (65 mg)3.45
Phase I, Dose Level 3 (85 mg)4.40
Phase II (MTD)3.45

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Maximum-tolerated Dose of Veliparib Defined as Highest Dose Level With Fewer Than 2 Dose Limiting Toxicities in 6 Patients as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase I)

The traditional 3+3 dose finding algorithm was used to estimate the maximum-tolerated dose of veliparib given concurrently with radiation therapy. The dose-limiting toxicity observation period was the first 10 weeks of therapy. Dose-limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with a few exceptions (see section 5.2.1.2 of the protocol document), any grade 2 non-hematologic toxicity that persisted for >7 days and considered medically significant that required treatment interruption; grade 3 or higher thrombocytopenia or grade 4 neutropenia; and any Veliparib related adverse event that led to a dose reduction or the permanent cessation of therapy. (NCT01514201)
Timeframe: 10 weeks

Interventionmg/m2/dose BID (Number)
Phase I Patients65

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Mean Apparent Clearance (CL/F) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

InterventionL/m^2/h (Mean)
Phase I, Dose Level 1 (50 mg)16.1
Phase I, Dose Level 2 (65 mg)13.2
Phase I, Dose Level 3 (85 mg)15.8
Phase II (MTD)11.7

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Number of Phase I Patients Who Experienced Dose Limiting Toxicities (DLTs)

DLTs were defined as any of the following adverse events that were at least possibly attributable to Veliparib observed during the dose finding phase (the first 10 weeks of therapy). Hematologic dose limiting toxicities included grade 3 and higher thrombocytopenia or grade 4 neutropenia. Non-hematologic dose limiting toxicities included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., nausea and vomiting of <5 days; fever or infection of <5 days; hypophosphatemia, hypokalemia, hypocalcemia or hypomagnesemia responsive to oral supplementation; elevation of transaminases that return to levels meeting eligibility criteria within 7 days), or any grade non-hematologic toxicity that persisted for >7 days and considered medically significant or sufficiently intolerable by patients that required treatment interruption. (NCT01514201)
Timeframe: 10 weeks

InterventionParticipants (Count of Participants)
Phase I, Dose Level 1 (50 mg)1
Phase I, Dose Level 2 (65 mg)0
Phase I, Dose Level 3 (85 mg)3

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Overall Survival

Overall survival was defined as the interval from date on treatment to date of death from any cause or to date of last follow-up. Patients who had not failed (died) at the time of analyses were censored at their last date of contact. The method of Kaplan and Meier was used to estimate overall survival. The 3-year estimate with a 95% confidence interval is reported. (NCT01514201)
Timeframe: Time from initiation of therapy to the date of death from any cause or to the date patient was known to be alive for surviving patients, assessed to up to 3 years

InterventionPercent probability (Number)
Phase II Patients + Phase I MTD Patients5.3

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Percentage of Participants Observed to Have Unacceptable Toxicity During the Intra-patient Dose Escalation of Temozolomide During Maintenance Therapy (Feasibility Analysis Population)

Unacceptable toxicities during maintenance included events at least possibly attributable to Veliparib and temozolomide (TMZ) such as any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., grade 3 nausea/vomiting <5 days, grade 3 fever or infection <5 days), grade 3+ thrombocytopenia, grade 4 neutropenia, delay >14 days in starting subsequent cycle due to neutrophil <1,000/mm3 or platelet <100,000/mm3. Maintenance therapy was initiated with 25 mg/m2 Veliparib and 135 mg/m2 of TMZ, with the possibility to escalate TMZ to 175 mg/m2 and 200 mg/m2 in courses 2 and 3, respectively, if no unacceptable toxicities occurred following one course of treatment at each of the dose levels to be tested. Intra-patient dose escalation to a given dose (135, 175, or 200 mg/m2) was halted based on rules employed in 3+3 designs. This dose escalation was intended for all patients but was halted early, during the phase I portion, as it was not well tolerated. (NCT01514201)
Timeframe: 28 days per treatment cycle

Intervention% of participants (Number)
Dose Level 1 (135 mg/m2)9
Dose Level 2 (175 mg/m2)40
Dose Level 3 (200 mg/m2)67

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Terminal Half-life (t1/2) for Veliparib [Pharmacokinetic Parameter]

During course 1, blood samples were collected pre-veliparib on day 1, at 0.5, 1, 2, and 6-8 hours after the first dose, pre-veliparib on day 4 (steady state), and 2 hours after the morning dose. Veliparib concentrations were measured using a liquid chromatography tandem mass spectrometry assay and pharmacokinetic parameters were evaluated using a non-compartmental analysis. (NCT01514201)
Timeframe: Up to day 4

InterventionHour (Mean)
Phase I, Dose Level 1 (50 mg)5.18
Phase I, Dose Level 2 (65 mg)2.62
Phase I, Dose Level 3 (85 mg)4.45
Phase II (MTD)2.18

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The Proportion of Patients Who Survive Progression-free for at Least 6 Months

This outcome captures whether or not the patient survived progression-free for at least 6 months, and is displayed as a proportion. (NCT01540565)
Timeframe: 6 months

InterventionProportion of patients (Number)
Treatment (Veliparib)0.54

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Proportion of Patients With Complete and Partial Tumor Response

Patients with complete and partial tumor response by RECIST V1.1 (per response evaluation criteria in Solid Tumors Criteria (RECIST V1.1) for target lesions and assessed by MRI (CT scan): Complete Response (CR), disappearance of all target lesions (confirmed at >= 4 weeks); Partial Response (PR) >= 30% decrease in the sum of the longest diameter of target lesions (confirmed at >= 4 weeks); Overall Response = CR + PR. (NCT01540565)
Timeframe: CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Repeat at other times if clinically indicated.Responses require confirmation at >= 4 wks from first documentation.

InterventionProportion of patients (Number)
Treatment (Veliparib)0.26

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Duration of PFS

The time from randomization until disease progression, death, or date of last contact. Endpoints are progression or death. Patients who are not observed with an endpoint are censored. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions (and >= 5 mm increase of target lesions), or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01540565)
Timeframe: CT scan/MRI if used to follow lesion for measurable disease every other cycle for the first 6 months, then every 3 months until progression. Patients who begin subsequent therapy without progression will be monitored for PFS for 5 years.

Interventionmonths (Median)
Treatment (Veliparib)8.18

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Duration of OS

Overall survival (NCT01540565)
Timeframe: Every cycle while patient is receiving protocol therapy. Patients will be monitored for survival after going off therapy for a 5 year period, every 3 months for the first 2 years, then every 6 months for the last 3 years.

InterventionMonths (Median)
Treatment (Veliparib)NA

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Proportion of Patients With Adverse Events as Assessed by CTCAE v4.0

Patients with grade 3 or greater Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. (NCT01540565)
Timeframe: After every cycle while on study therapy. Followed for late adverse events up to 30 days after completing therapy.

InterventionProportion of patients (Number)
Treatment (Veliparib)0.32

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Progression-free Survival (PFS)

Time from randomization to disease progression or death. (NCT01576172)
Timeframe: Up to 42 months

Interventionmonths (Median)
Arm I (Abiraterone Acetate and Prednisone)10.1
Arm II (Abiraterone Acetate, Prednisone, and Veliparib)11.0

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Objective Response Rates in Patients With Measurable Disease.

Overall response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01576172)
Timeframe: Up to 3 years

InterventionParticipants (Count of Participants)
Arm I (Abiraterone Acetate and Prednisone)18
Arm II (Abiraterone Acetate, Prednisone, and Veliparib)24

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Grade 4 or 5 Adverse Events

Grade 4 or greater toxicity graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 at least possibly related to treatment. (NCT01576172)
Timeframe: 30 days after completion of study treatment

InterventionParticipants (Count of Participants)
Arm I (Abiraterone Acetate and Prednisone)1
Arm II (Abiraterone Acetate, Prednisone, and Veliparib)3

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Confirmed Prostate-specific Antigen (PSA) Response Rate

50% or greater decline in PSA from baseline. (NCT01576172)
Timeframe: Up to 3 years

InterventionParticipants (Count of Participants)
Arm I (Abiraterone Acetate and Prednisone)46
Arm II (Abiraterone Acetate, Prednisone, and Veliparib)55

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Rates of PSA Decline

Change in PSA from baseline to 12 weeks (NCT01576172)
Timeframe: 12 weeks

Interventionng/ml (Mean)
Arm I (Abiraterone Acetate and Prednisone)-41.1
Arm II (Abiraterone Acetate, Prednisone, and Veliparib)-52.9

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Progression-free Survival, Calculated as the Proportion of Patients Alive and Without Evidence of Disease

Compared across the two arms using a Fisher exact test. (NCT01638546)
Timeframe: From randomization to time of progression or death, whichever occurs first, assessed at 4 months

Interventionparticipants (Number)
Arm I (Veliparib and Temozolomide)18
Arm II (Placebo and Temozolomide)11

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Overall Survival

Estimated in each treatment group using Kaplan-Meier method. Group comparisons will be performed using log-rank test. (NCT01638546)
Timeframe: From randomization to time of death

Interventionmonths (Median)
Arm I (Veliparib and Temozolomide)8.2
Arm II (Placebo and Temozolomide)7

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Number of Participants With Adverse Events

Tabulated According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. Summary level. (NCT01638546)
Timeframe: From the start of treatment until 30 days from coming off treatment

InterventionParticipants (Count of Participants)
Arm I (Veliparib and Temozolomide)52
Arm II (Placebo and Temozolomide)45

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Overall Response (ORR) by RECIST 1.1 Criteria

Corresponding exact two-sided 95% confidence intervals will be calculated and reported in both arms of the study. Comparisons between treatment arms will be performed using Fisher-exact test. (NCT01638546)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 4 months

Interventionparticipants (Number)
Arm I (Veliparib and Temozolomide)20
Arm II (Placebo and Temozolomide)6

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Progression Free Survival (Phase II)

Profession free survival (PFS) is defined as time from randomization to date of disease progression or death from any cause, whichever occurred first. Patients who had not experienced an event of interest by the time of analysis were censored at the date they were last known to be alive and progression-free. Tumor response was evaluated via Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, and progression was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Median PFS was estimated using the Kaplan-Meier method. (NCT01642251)
Timeframe: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of first documented progression or death. No specific requirements if patient is > 3 years from registration

,
Interventionmonths (Median)
Overall samplePatients within the male/abnormal LDH stratumPatients not within the male/abnormal LDH stratum
Phase II: Arm D (Veliparib)6.16.26.0
Phase II: Arm E (Placebo)5.55.15.6

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Overall Survival (OS)

Overall survival (OS) is defined as time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method. (NCT01642251)
Timeframe: Assessed every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration until the date of death. No specific requirements if patient is > 3 years from registration

Interventionmonths (Median)
Phase II: Arm D (Veliparib)10.3
Phase II: Arm E (Placebo)8.9

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Neurotoxicity Total Score Change Between Baseline and 3 Months After Treatment Start

Neurotoxicity total score was measured by the 11 items in the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire. Each item was scored from 0-4. The severity of neurotoxicity was measured by the total score of the 11 items, ranged from 0 to 44. Lower values of the FACT/GOG-Ntx neurotoxicity total score indicate higher neurotoxicity. (NCT01642251)
Timeframe: assessed at baseline and 3 months after treatment initiation

Interventionunits on a scale (Mean)
Phase II: Arm D (Veliparib)-0.1
Phase II: Arm E (Placebo)-1.8

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Overall Response Rate (ORR)

Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Complete response (CR) was defined as disappearance of all target lesions. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Overall response rate= (CR+PR)/all eligible and treated patients (NCT01642251)
Timeframe: assessed every 6 weeks while on study, then every 3 months for patients < 2 years from registration and every 6 months if patient is 2- 3 years from registration.

Interventionpercentage of patients (Number)
Phase II: Arm D (Veliparib)72
Phase II: Arm E (Placebo)66

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Best Tumor Response Rate

"Best tumor response rate was calculated as the percentage of participants with a complete response or partial response, as determined by brain scan imaging (magnetic resonance image or computed tomography) by a central imaging vendor. Response was assessed according to the modified bidimensional criteria:~Complete response required all of the following: complete disappearance of all target and non-target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease; no systemic corticosteroid dose.~Partial response required all of the following: ≥ 50% decrease compared with baseline in the size of all target lesions sustained for at least 4 weeks; no new lesions, including no new leptomeningeal disease and no unequivocal progression of non-target lesions, which, even in presence of stable disease or progressive disease in target lesions, was significant enough to qualify as progression; stable or reduced daily total systemic corticosteroid dose." (NCT01657799)
Timeframe: From randomization up to 24 months

Interventionpercentage of participants (Number)
Placebo BID + WBRT41.2
Veliparib 50 mg BID + WBRT36.9
Veliparib 200 mg BID + WBRT42.2

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Overall Survival

Overall survival was defined as the number of days from the date of randomization to the date of death. All events of death were included, regardless of whether the event occurred while the participant was still taking study treatment or after treatment was discontinued. If a participant had not died, the data were censored at the date the participant was last known to be alive. (NCT01657799)
Timeframe: From randomization up to 36 months

Interventiondays (Median)
Placebo BID + WBRT185
Veliparib 50 mg BID + WBRT209
Veliparib 200 mg BID + WBRT209

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Time to Clinical Brain Metastasis Progression

Time to clinical brain metastases progression was defined as the number of days from randomization to the date of the first experience of clinical brain metastases progression, as assessed by a team of neuro-oncology experts (Event Review Board). All events of clinical brain metastasis progression were included, regardless of whether the event occurred while the participant was still receiving study treatment or had previously discontinued study treatment. If a participant did not have an event of clinical brain metastases progression, their data were censored at the date of the last available clinical disease progression assessment. Time to clinical brain metastasis progression was estimated for each treatment group using Kaplan-Meier methodology. (NCT01657799)
Timeframe: From randomization up to 24 months

Interventiondays (Median)
Placebo BID + WBRT348
Veliparib 50 mg BID + WBRT286
Veliparib 200 mg BID + WBRT255

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Time to Intracranial Progression (Radiographic)

Time to intracranial progression (radiographic) was defined as the number of days from the date of randomization to the date of the first intracranial progression, as determined by brain scan imaging (magnetic resonance image [MRI]/ computed tomography [CT] scan) by a central imaging vendor. All confirmed events of intracranial progression were included, regardless of whether the event occurred while the participant was still taking study treatment or had previously discontinued study treatment. If the participant did not have a confirmed event of intracranial progression, their data were censored at the date of the last available intracranial progression assessment. Time to intracranial progression (radiographic) was estimated for each treatment group using Kaplan-Meier methodology. (NCT01657799)
Timeframe: From randomization up to 24 months

Interventiondays (Median)
Placebo BID + WBRT259
Veliparib 50 mg BID + WBRT226
Veliparib 200 mg BID + WBRT224

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Toxicity (Phase I and Phase II)

Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event. (NCT01711541)
Timeframe: upt to 5 years

,,,,
InterventionParticipants (Count of Participants)
Grade 3 Adverse EventGrade 4 Adverse EventGrade 5 Adverse Event
Dose Level 0030
Dose Level 0B210
Dose Level 1210
Dose Level 2400
Dose Level 3610

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Dose Limiting Toxicity (Phase I)

"Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.~The following events are considered DLTs: Grade 4 neutropenia (ANC < 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.~The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT." (NCT01711541)
Timeframe: Up to 3 weeks

InterventionParticipants (Count of Participants)
Dose Level 00
Dose Level 0B0
Dose Level 10
Dose Level 20
Dose Level 31

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Count of Participants That Achieve Pathologic Complete Response (PCR)

PCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin (H&E) evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes. (NCT01818063)
Timeframe: 36 months following surgery

InterventionParticipants (Count of Participants)
Arm 1 (Paclitaxel, Carboplatin)3
Arm 2 (Veliparib, Paclitaxel, Carboplatin)3

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Number of Participants With an Objective Response

ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. (NCT01827384)
Timeframe: Up to 30 days after completion of study treatment, up to 75 months

,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
TAC1 -> TAC400
TAC200
TAC2 -> TAC100
TAC2 -> TAC300
TAC301
TAC3 -> TAC100
TAC3 -> TAC1 -> TAC400
TAC3 -> TAC400
TAC400
TAC4 -> TAC100
TAC4 -> TAC200
TAC4 -> TAC300
Treatment Assignment Code 1 (TAC1)00

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Proportion of Participants With 4 Month Progression-free Survival (PFS)

Time from random assignment to progression or death from any cause (whichever comes first). Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions is also considered progressions. (NCT01827384)
Timeframe: 4 months

Interventionproportion of participants (Number)
Treatment Assignment Code 1 (TAC1)0.23
TAC1 -> TAC40.00
TAC20.22
TAC2 -> TAC10.00
TAC2 -> TAC31.00
TAC30.41
TAC3 -> TAC10.50
TAC3 -> TAC1 -> TAC40.00
TAC3 -> TAC40.00
TAC40.13
TAC4 -> TAC10.29
TAC4 -> TAC20.00
TAC4 -> TAC30.00

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Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01827384)
Timeframe: Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.

InterventionParticipants (Count of Participants)
Treatment Assignment Code 1 (TAC1)13
TAC1 -> TAC41
TAC29
TAC2 -> TAC11
TAC2 -> TAC31
TAC322
TAC3 -> TAC12
TAC3 -> TAC1 -> TAC41
TAC3 -> TAC42
TAC415
TAC4 -> TAC17
TAC4 -> TAC21
TAC4 -> TAC32
Participants Enrolled But Not Treated2

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Objective Tumor Response

"Defined as complete response (CR) or partial response (PR) as specified in the Revised Assessment in Neuro-Oncology criteria. An objective tumor response will be evaluated for each patient and the tumor response count will be summarized for each arm and compared using the Chi-square test. For CR, all of the following must be true:~disappearance of all enhancing measurable and non-measurable disease; no new enhancing lesions; stable or improved non-enhancing lesions; patients must be off corticosteroids; stable or improved clinically~A PR requires all of the following: > 50% decrease in sum of products of perpendicular diameters of all measurable enhancing lesions compared with baseline; no progression of non-measurable disease; no new lesions; stable or improved non-enhancing lesions on same or lower dose of corticosteroids compared with baseline scan; steroid dose should be same or lower compared with baseline scan; stable or improved clinically" (NCT02152982)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Arm I (Temozolomide, Veliparib)34
Arm II (Temozolomide, Placebo)37

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Interaction With Optune Device

Cox proportional hazards model will be used to evaluate whether there is a potential interaction between the treatment arm and the Optune device. If an interaction is detected, separate analyses of treatment effect (using Cox models) will be done for patients treated with the Optune device and patients who were not treated with the Optune device. (NCT02152982)
Timeframe: 5 years

,
Interventionparticipants (Number)
Reporting actual Optune useNo actual Optune use
Arm I (Temozolomide, Veliparib)33125
Arm II (Temozolomide, Placebo)33135

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Progression-free Survival (PFS)

"The distribution of PFS for each arm will be estimated using the Kaplan-Meier method, and be compared using Cox proportional hazard models with all stratification factors adjusted. Progression (PD): Defined by any of the following:~> 25% increase in sum of products of perpendicular diameters of enhancing lesions, compared with the smallest tumor measurement obtained either at baseline or best response~Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared with baseline scan or best response after therapy initiation (stable doses of steroids include patient not on steroids) not caused by comorbid events~Any new lesion~Clear clinical deterioration not attributable to other causes apart from tumor or change in corticosteroid dose~Failure to return for evaluation as a result of death or deteriorating condition~Clear progression of non-measurable disease" (NCT02152982)
Timeframe: 83 months

Interventionmonths (Median)
Arm I (Temozolomide, Veliparib)12.1
Arm II (Temozolomide, Placebo)13.2

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Overall Survival (OS)

The distribution of OS for each arm will be estimated using the Kaplan-Meier method and compared with a stratified logrank test. (NCT02152982)
Timeframe: 83 months

Interventionmonths (Median)
Arm I (Temozolomide, Veliparib)24.8
Arm II (Temozolomide, Placebo)28.1

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Overall Adverse Event Rates for Grade 3 or Higher Adverse Events

Assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5 beginning April 1, 2018). The overall adverse event rates for grade 3 or higher adverse events will be summarized and be compared using Chi-Square or Fisher's Exact tests between treatment arms. The maximum grade for each type of treatment-related adverse event will be recorded for each patient, and frequency tables for each arm will be reviewed to determine patterns. Treatment-related adverse events will be tabulated for each arm. (NCT02152982)
Timeframe: 5 years

Interventionparticipants with at least 1 grade 3+ AE (Number)
Arm I (Temozolomide, Veliparib)94
Arm II (Temozolomide, Placebo)137

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Progression-Free Survival (PFS)

Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology. (NCT02163694)
Timeframe: From randomization until the primary analysis data cut-off date of 05 April 2019; the median duration of follow-up was 35.5 months

Interventionmonths (Median)
Veliparib Placebo With Carboplatin and Paclitaxel12.6
Veliparib With Carboplatin and Paclitaxel14.5

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Progression Free Survival (PFS) in All Participants

"Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first.~PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.~PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death." (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy6.7
Veliparib + Carboplatin + Paclitaxel5.9

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Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup

Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive. (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy9.2
Veliparib + Carboplatin + Paclitaxel11.2

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Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup

"Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.~CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions." (NCT02264990)
Timeframe: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.

Interventionpercentage of participants (Number)
Investigator's Choice Chemotherapy30.0
Veliparib + Carboplatin + Paclitaxel22.5

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Objective Response Rate (ORR) in All Participants

"Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.~CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions." (NCT02264990)
Timeframe: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.

Interventionpercentage of participants (Number)
Investigator's Choice Chemotherapy29.0
Veliparib + Carboplatin + Paclitaxel26.2

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Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup

"Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first.~PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.~PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death." (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy5.2
Veliparib + Carboplatin + Paclitaxel6.3

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Overall Survival in All Participants

Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive. (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy12.1
Veliparib + Carboplatin + Paclitaxel12.1

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Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)16.9
Etoposide Cycle 2 Day 1 (No Veliparib)16.4

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Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

"A DLT was defined as any of the following drug-related toxicities, graded according to the Common Toxicity Criteria for Adverse Events (CTCAE), V.4.0:~Events associated with treatment delay >14 days in initiating Cycle 2 therapy:~Grade 4 thrombocytopenia, neutropenia, or febrile neutropenia, or Grade 3 febrile neutropenia with fever for > 7 days~Grade ≥ 3 non-hematologic toxicity with ≥ 2 grade increase from baseline and attributed to veliparib treatment, excluding nausea or vomiting for ≤ 48 hours or inadequately treated, electrolyte abnormalities resolving in ≤ 24 hours, hypersensitivity reactions or alopecia~Grade 2 non-hematologic toxicity of ≥ 2 grade increase from baseline, attributed to veliparib treatment requiring delay of >14 days in initiation of Cycle 2~Any toxicity of ≥ 2-grade increase from baseline, attributed to veliparib and requiring a dose modification in Cycle 1 or omission of carboplatin, >1 daily etoposide dose, or >30% veliparib doses in Cycle 1" (NCT02289690)
Timeframe: Cycle 1 Day -2 to pre-dose on Cycle 2 Day 1 (23 days)

InterventionParticipants (Count of Participants)
Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide1
Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide1

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Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib

The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg*h/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide3.18
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide4.24
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide7.51
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide6.66
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide9.29

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Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionhours (Median)
Etoposide Cycle 1 Day 1 (With Veliparib)0.9
Etoposide Cycle 2 Day 1 (No Veliparib)0.9

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Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib

Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionhours (Median)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide2.0
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide1.0
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide1.5
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide2.0
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide1.0

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Phase 2: Objective Response Rate

"Objective response rate (ORR) is defined as the percentage of participants with objective response (confirmed) as assessed by the investigator using RECIST version 1.1. Objective response includes both complete response (CR) and partial response (PR). Response must be confirmed at a subsequent tumor assessment at least 28 days apart. Participants with no post-baseline confirmed response were counted as non-responders.~CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. No new lesions.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and no new lesions." (NCT02289690)
Timeframe: Tumor assessments were performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until disease progression; median time on follow-up was 7.3, 7.1, and 8.9 months in each group respectively.

Interventionpercentage of participants (Number)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib77.0
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo59.3
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo63.9

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Phase 2: Overall Survival

Overall survival (OS) is defined as the time from the date of randomization to the date of death. If a participant did not die on or prior to the cut-off for OS analysis, the participant's data were censored at the date of their last known alive date, which is defined as the last date of the last survival follow-up visit, the start date of the last AE, the start date or end date of the last dose of any study drugs, the last lab and vital sign collection date, or the last disease assessment date, whichever occurred last. (NCT02289690)
Timeframe: From randomization until the end of study; median time on follow-up was 10.0, 8.6, and 11.7 months in each treatment group respectively.

Interventionmonths (Median)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib10.1
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo10.0
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo12.4

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Phase 2: Progression-free Survival

"Progression-free survival (PFS) is defined as the time from the date of randomization to the date of earliest radiographic disease progression or death provided no radiographic disease progression occurred.~If a participant did not have an event of disease progression and had not died on or prior to the cutoff for PFS analysis, the participant's data was censored at the date of their last disease assessment or randomization date provided participant did not have any post-baseline disease assessment.~Disease assessments were performed using computed tomography according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.~Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions." (NCT02289690)
Timeframe: From randomization up to the date the 126th PFS event was reached; Median time on follow-up was 7.3, 7.1, and 8.9 months in each treatment group respectively.

Interventionmonths (Median)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib5.8
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo5.7
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo5.6

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Phase 1: Number of Participants With Adverse Events

"The intensity of each adverse event (AE) was assessed utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, and according to the following: Grade 1 (Mild): AE is transient and easily tolerated by the participant; Grade 2 (Moderate): AE causes the participant discomfort and interrupts the participant's usual activities; Grade 3/4 (Severe): The adverse event causes considerable interference with the participant's usual activities and may be incapacitating or life-threatening; Grade 5: Death.~Serious adverse events were those that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in congenital anomaly, or persistent or significant disability/incapacity." (NCT02289690)
Timeframe: From first dose of any study drug to 30 days after the last dose; the median duration of treatment with veliparib across all groups in Phase 1 was 127.5 days.

,,,,,,
InterventionParticipants (Count of Participants)
Any adverse eventAny AE Grade 3/4Any serious adverse eventAny fatal adverse event
Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide3310
Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide4431
Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide3321
Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide141460
Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide4430
Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide8730
Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide4430

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Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg*h/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)112
Etoposide Cycle 2 Day 1 (No Veliparib)99.5

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Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg*h/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)102
Etoposide Cycle 2 Day 1 (No Veliparib)94.7

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Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib

The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg*h/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide4.07
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide5.25
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide9.71
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide8.35
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide11.6

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Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib

Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide0.620
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide1.00
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide1.39
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide1.44
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide1.99

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Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-∞) is calculated as AUC(0-∞) / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng*h/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)1120
Etoposide Cycle 2 Day 1 (No Veliparib)1020

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Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-t) is calculated as AUC(0-t) / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng*h/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)1020
Etoposide Cycle 2 Day 1 (No Veliparib)952

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Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib

The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. Dose normalized AUC(0-12) is calculated as AUC(0-12) / veliparib dose in mg. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng*h/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide50.9
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide43.8
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide60.7
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide41.7
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide48.5

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Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib

The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. Dose normalized AUC(0-8) is calculated as AUC(0-8) / veliparib dose in mg. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng*h/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide39.8
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide35.3
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide46.9
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide33.3
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide38.7

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Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. Dose normalized Cmax is calculated as Cmax / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)169
Etoposide Cycle 2 Day 1 (No Veliparib)170

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Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib

"Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.~Dose normalized Cmax is calculated as Cmax / veliparib dose in mg." (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide7.75
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide8.35
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide8.66
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide7.19
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide8.31

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Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib

The terminal half-life of etoposide was estimated using using non-compartmental methods. Values reported represent the harmonic mean ± pseudo-standard deviation. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionhours (Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)5.7
Etoposide Cycle 2 Day 1 (No Veliparib)5.0

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Overall Survival (OS): Time to Event

Overall survival was defined as the number of days from the date that the participant was randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurred while the participant was still taking or had discontinued study drug. If a participant had not died, the data were censored at the date last known to be alive. The OS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the OS distribution quartiles are provided. (NCT02305758)
Timeframe: Survival information was to be collected 4 wks after the last study visit, continuing every 4 wks for 1 yr, then every 8 wks for up to 2 more yrs or until death. The maximum observed follow up duration at the overall survival analysis time was 914 days.

,
Interventiondays (Number)
25th Quartile50th Quartile75th Quartile
Placebo + FOLFIRI ± Bevacizumab512811NA
Veliparib + Modified FOLFIRI ± Bevacizumab557770NA

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Objective Response Rate (ORR)

ORR was defined as the proportion of participants with a complete (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) for target lesions, assessed by computed tomography (CT). Complete response (CR) was defined as disappearance of all target lesions; partial response (PR) ≥30% decrease in the the sum of diameters of target lesions, taking as reference the baseline sum diameters. For participants who underwent surgery, ORR was not evaluated after surgery. (NCT02305758)
Timeframe: Per protocol, post-baseline tumor assessment was conducted every 8 weeks from Cycle 1 Day 1 until radiographic progression. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

InterventionParticipants (Count of Participants)
Veliparib + Modified FOLFIRI ± Bevacizumab37
Placebo + FOLFIRI ± Bevacizumab40

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Progression-Free Survival (PFS): Time to Event

PFS was defined as the number of days from the date the participant was randomized to the date the participant experienced an event of disease progression or death, whichever occurred first. All events of disease progression were included, whether the participant was still taking or had discontinued study drug. Events of death were included for participants who had not experienced an event of disease progression, if the death occurred within 8 weeks of the last evaluable disease progression assessment. If the participant did not have an event of disease progression and the participant had not died as defined above, data were censored at the date of the participant's last evaluable disease progression assessment. The PFS distribution was estimated using Kaplan-Meier methodology. Point estimates and 95% confidence intervals (95% CIs) for the PFS distribution quartiles are provided. (NCT02305758)
Timeframe: Every 8 weeks from Cycle 1, Day 1 until radiographic progression was observed. The maximum observed follow up duration at the progression-free survival analysis time was 579 days.

,
Interventiondays (Number)
25th Quartile50th Quartile75th Quartile
Placebo + FOLFIRI ± Bevacizumab213337512
Veliparib + Modified FOLFIRI ± Bevacizumab221361534

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Duration of Overall Response (DOR)

Duration of overall response was defined as time from the date of first response (CR or PR) to the earliest documentation of radiographic progressive disease or death due to disease progression, calculated using Kaplan-Meier methods. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. (NCT02412371)
Timeframe: Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Interventionmonths (Median)
Total30.4

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Progression-free Survival

"Progression-free survival (PFS) was defined as the time from first dose of study drug to the date of earliest radiographic disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, and was calculated using Kaplan-Meier methods. All radiographic disease progression was included regardless whether the event occurred while the participant was taking study drug or had previously discontinued study drug. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. Participants with no post-baseline disease assessment were censored at first dose date plus 1 day.~Progressive disease (PD) was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions." (NCT02412371)
Timeframe: From first dose until end of study; maximum time on follow-up was approximately 46 months.

Interventionmonths (Median)
Total19.6

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Overall Survival

Overall survival (OS) was defined as the time from the participant's first dose of study drug to the date of death, and was calculated using Kaplan-Meier methods. Participants who did not die were censored at the date of last study visit or the last known date to be alive, whichever was later. (NCT02412371)
Timeframe: From first dose of study drug until end of study; maximum time on follow-up was approximately 46 months.

Interventionmonths (Median)
Total32.6

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Objective Response Rate

"Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders.~Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Response must have been confirmed 4 weeks after the first documentation." (NCT02412371)
Timeframe: Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Interventionpercentage of participants (Number)
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT50.0
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT50.0
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT100.0
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT62.5
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT72.7
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT0.0

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Number of Participants With Dose-limiting Toxicities (DLTs)

"DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.~Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity~Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy)~≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia~≥G2 seizure~G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours~Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT~Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours" (NCT02412371)
Timeframe: For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.

InterventionParticipants (Count of Participants)
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT1
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT2

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Progression-Free Survival (PFS) in the BRCA-deficient Population

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo22.0
Veliparib + Carboplatin + Paclitaxel -> Placebo21.1
Veliparib + Carboplatin + Paclitaxel -> Veliparib34.7

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Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.~." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo20.5
Veliparib + Carboplatin + Paclitaxel -> Placebo18.1
Veliparib + Carboplatin + Paclitaxel -> Veliparib31.9

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Progression-Free Survival (PFS) in the Intention-to-treat Population

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.~The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo17.3
Veliparib + Carboplatin + Paclitaxel -> Placebo15.2
Veliparib + Carboplatin + Paclitaxel -> Veliparib23.5

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Number of Participants With RAD51 Recombinase (Rad51), Phosphorylated Histone H2AX (γH2AX), Phosphorylated at Serine 343 (pS343)-Nibrin (Nbs1), and Phosphorylated KRAB-associated Protein 1 (pKAP-1) Induced After Treatment

Biopsies were collected at Cycle 1 Day 1, and Cycle 1 Day 9 and markers Rad51, γH2AX, pS343-Nbs1, and pKAP-1 were measured for deoxyribonucleic acid (DNA) damage and apoptosis by immunofluorescence assays (IFA). (NCT02723864)
Timeframe: Cycle 1 Day 1, and Cycle 1 Day 9 (i.e., one cycle = 21 days)

InterventionParticipants (Count of Participants)
Rad51 induced after veliparib and cisplatin treatment on Cycle 1, Day 1Rad51 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9γH2AX induced after veliparib and cisplatin treatment on Cycle 1, Day 1γH2AX induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9pS343-Nbs1 induced after veliparib and cisplatin treatment on Cycle 1, Day 1pS343-Nbs1 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9pKap1 induced after veliparib and cisplatin treatment on Cycle 1, Day 1pKap1 induced after veliparib, cisplatin and M6620 treatment on Cycle 1, Day 9
Dose Level 655001000

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Number of Participants With a Best Response to the Antitumor Activity of Veliparib (ABT-888), an Oral PARP Inhibitor, and VX-970, an ATR Inhibitor, in Combination With Cisplatin

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, and the appearance of one or more new lesions. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02723864)
Timeframe: 4 cycles (i.e., one cycle = 21 days)

,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot Evaluable for Response
Dose Level 100120
Dose Level 200210
Dose Level 302310
Dose Level 400430
Dose Level 500300
Dose Level 6031057
Dose Level 700330

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Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT02723864)
Timeframe: Date treatment consent signed to date off study, approximately 6 months and 20 days, 3 months and 17 days, 24 months and 13 days, 9 months and 8 days, 5 months and 18 days, 35 months and 20 days, and 5 months and 22 days for each Arm/Group respectively.

InterventionParticipants (Count of Participants)
Dose Level 13
Dose Level 23
Dose Level 36
Dose Level 47
Dose Level 53
Dose Level 625
Dose Level 76

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Progression Free Survival (PFS)

From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. (NCT02890355)
Timeframe: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Interventionmonths (Median)
Arm I (Veliparib and mFOLFIRI)2.1
Arm II (FOLFIRI)2.9

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Overall Survival (OS)

"OS: time to death by any cause from randomized treatment arm assignment.~The log-rank test with stratification was used by prior systemic treatment for metastatic disease. Distributions of overall survival in arms 1 and 2 were estimated using the method of Kaplan-Meier." (NCT02890355)
Timeframe: Up to 3 years

Interventionmonths (Median)
Arm I (Veliparib and mFOLFIRI)5.4
Arm II (FOLFIRI)6.5

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Overall Response Rate, ORR

Overall response rate (ORR) is defined as the proportion of participants who have a confirmed and unconfirmed, partial or complete response to therapy. (NCT02890355)
Timeframe: Up to 3 years post registration

Interventionproportion of participants (Number)
Arm I (Veliparib and mFOLFIRI)0.09
Arm II (FOLFIRI)0.10

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Duration of Response (DoR)

"DoR: time from date of first documentation of response (complete response, CR, or partial response, PR) to date of first documentation of progression or symptomatic deterioration, or death due to any cause among participants, who achieve a response (CR or PR).~The distribution of DoR in each treatment arm will be estimated using the Kaplan-Meier method." (NCT02890355)
Timeframe: Up to 3 years post registration

Interventionmonths (Median)
Arm I (Veliparib and mFOLFIRI)3.4
Arm II (FOLFIRI)5.1

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Disease Control Rate

Disease control rate (DCR) is defined as the proportion of participants who have a confirmed and unconfirmed, partial, complete or stable response to therapy. (NCT02890355)
Timeframe: Up to 3 years post registration

Interventionproportion of participants (Number)
Arm I (Veliparib and mFOLFIRI)0.32
Arm II (FOLFIRI)0.47

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Rate of Sphincter Preservation

Sphincter preservation means that the surgical procedure used to remove the tumor did not disturb the sphincter muscle. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment. (NCT02921256)
Timeframe: Up to 3 years

Interventionpercentage of participants (Mean)
Arm Ia (mFOLFOX6, RT, Capecitabine)52.5
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)59.3
Arm Ib (mFOLFOX6, RT, Capecitabine, Pembrolizumab)71.0
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)59.4

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Rate of Pathologic Complete Response (Nodes and Tumor) ypT0 and ypN0

Pathologic Complete Response means no remaining cancer detectable in the pathology sample. Analyzed by a logistic regression model that controls for the stratification factors (cT-stage and cN-stage). Observed proportions along with confidence intervals will be presented by treatment. (NCT02921256)
Timeframe: Up to 3 years

Interventionpercentage of participants (Mean)
Arm Ia (mFOLFOX6, RT, Capecitabine)21.6
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)33.8
Arm Ib (mFOLFOX6, RT, Capecitabine)29.4
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)31.9

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Neoadjuvant Rectal Cancer (NAR) Score

A linear regression model that controls for the stratification factors (cT-stage and cN-stage) will be used. Mean NAR scores along with standard errors and confidence intervals will be reported by treatment. The NAR score ranges from zero to 100 with lower values corresponding to better prognosis. (NCT02921256)
Timeframe: Baseline to up to 3 years

Interventionscore on a scale (Mean)
Arm Ia (mFOLFOX6, RT, Capecitabine)12.6
Arm II (mFOLFOX6, RT, Capecitabine, Veliparib)13.7
Arm Ib (mFOLFOX6, RT, Capecitabine)14.1
Arm III (mFOLFOX6, RT, Capecitabine, Pembrolizumab)11.5

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ORR (Overall Response Rate)

"Overall response rate or ORR, (partial response (PR) + complete response (CR)) will be evaluated using RECIST criteria v1.1 or Lugano 2014 classification for assessment of Lymphoma.~Per RECIST v. 1.1: PR= : At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR= Disappearance of all target lesions.~Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.~Per Lugano 2014 classification, scored on a Deauville 5-point scale (an internationally-recommended scale using FDG PET-CT in the initial staging and assessment of treatment response in Hodgkin lymphoma (HL) and certain types of non-Hodgkin lymphomas (NHL).~Partial metabolic response (PMR): score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size.~Complete metabolic response (CMR): Score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass" (NCT03061188)
Timeframe: after 2 cycles at first response time point (1 cycle = 28 days)

,,
Interventionparticipants (Number)
Complete ResponsePartial Response
Velaparib PO Twice Daily + Nivolumab (Cohort 1)00
Velaparib PO Twice Daily + Nivolumab (Cohort 2)00
Velaparib PO Twice Daily + Nivolumab (Phase 2)00

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Clinical Benefit Rate (CBR)

CBR= stable disease for ≥12 weeks + Partial Response + Complete Response per RECIST v1.1 for solid tumors or Lugano 2014 classification for lymphomas. Lugano scored on a Deauville 5-point scale. RECIST v. 1.1: PR= : At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. CR= Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. Lugano 2014 classification: PR: score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size. CR: Score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass. SD: No metabolic response, Score 4 or 5 with no significant change in FDG uptake from baseline at interim or end of treatment. (NCT03061188)
Timeframe: From the start of treatment and every 2 cycles during treatment where 1 cycle =28 days, average number of cycles is 4 and range of cycles is 1-12.

,,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable Disease for or ≥12 weeks
Velaparib PO Twice Daily + Nivolumab (Cohort 1)000
Velaparib PO Twice Daily + Nivolumab (Cohort 2)004
Velaparib PO Twice Daily + Nivolumab (Phase 2)002

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Overall Survival (OS)

Overall Survival is defined as the time from treatment initiation until death due to any cause, assessed up to 3 years from the start of treatment. (NCT03061188)
Timeframe: From the start of treatment and up to 3 years, where 1 cycle =28 days, and range of cycles is 1-12.

Interventionmonths (Median)
Velaparib PO Twice Daily + Nivolumab (Cohort 1)5.82
Velaparib PO Twice Daily + Nivolumab (Cohort 2 + Phase 2)11.79

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Number of Patients Alive and Progression Free at 24 Weeks

To evaluate the number of patients alive and progression free at 24 weeks. -Per RECIST v. 1.1 (for solid tumors) progression is defined as : At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression.) -Lugano 2014 classification, scored on a Deauville 5-point scale (an internationally-recommended scale using FDG PET-CT in the initial staging and assessment of treatment response i Hodgkin lymphoma (HL) and certain types of non-Hodgkin lymphomas (NHL). Per Lugano criteria: Partial metabolic disease (PMD):Score 4 or 5 with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment. (NCT03061188)
Timeframe: At 24 weeks

Interventionparticipants (Number)
Velaparib PO Twice Daily + Nivolumab (Cohort 1)0
Velaparib PO Twice Daily + Nivolumab (Cohort 2)1
Velaparib PO Twice Daily + Nivolumab (Phase 2)2

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Maximum Tolerated Dose (MTD)

"The MTD will be defined as the highest dose that causes dose-limiting toxicities (DLTs) in <2 of 6 patients. Toxicity will be assessed using CTCAEv4.03. A DLT is defined as an Adverse Event (AE) or abnormal laboratory value assessed as at least possibly related to the study medication, occurs ≤ 28 days (1 cycle) following the first dose of veliparib and nivolumab and meets any of the following criteria:~Grade ≥ 3 non-hematologic toxicities that represent at least a 2-grade increase from baseline excluding Nausea, vomiting, diarrhea lasting ≤48 hours, Electrolyte abnormalities resolving within ≤24 hours, Hypersensitivity reactions,and Alopecia.~Grade 4 thrombocytopenia (platelets < 25.0 x 109 /L) Grade 3 thrombocytopenia with bleeding (platelets < 0.5 x 109 /L) 5. Grade 3 febrile neutropenia with fever lasting for > 7 days 6. Grade 4 febrile neutropenia of any duration 7. Dosing delay due to toxicity for > 14 consecutive days from the date nivolumab or veliparib is due." (NCT03061188)
Timeframe: First Cycle of Treatment with velaparib and nivolumab (28 days)

Interventionmg (Number)
Velaparib PO Twice Daily + Nivolumab (Phase 1)400

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Progression Free Survival (PFS)

To evaluate Progression Free Survival (PFS) for patients treated with nivolumab and veliparib, defined as the time from treatment initiation to documented disease progression. Evaluated by RECIST criteria v1.1 for solid tumors or Lugano 2014 classification for assessment of Lymphoma. RECIST v. 1.1 definition for PD (Progressive disease): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Lugano 2014 classification, scored on a Deauville 5-point scale (an internationally-recommended scale using FDG PET-CT in the initial staging and assessment of treatment response in Hodgkin lymphoma (HL) and certain types of non-Hodgkin lymphomas (NHL). Per Lugano criteria: Partial metabolic disease (PMD):Score 4 or 5 with an increase in intensity of uptake from baseline and/or new FDG-avid foci consistent with lymphoma at interim or end-of-treatment assessment. (NCT03061188)
Timeframe: From the start of treatment and every 2 cycles during treatment, and up to three years, where 1 cycle =28 days, and range of cycles is 1-12.

Interventionmonths (Median)
Velaparib PO Twice Daily + Nivolumab (Cohort 1)2.07
Velaparib PO Twice Daily + Nivolumab (Cohort 2 + Phase 2)1.94

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