| ID Source | ID |
|---|---|
| PubMed CID | 71300725 |
| SCHEMBL ID | 14997572 |
| MeSH ID | M0585598 |
| Synonym |
|---|
| etirinotecan pegol |
| SCHEMBL14997572 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Most adverse events related to study drug were gastrointestinal disorders and were more frequent at higher doses of etirinotecan pegol." | ( A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Alemany, C; Anthony, S; Basche, M; Borad, MJ; Cohn, A; Eldon, MA; Hamm, JT; Hinshaw, I; Hoch, U; Jameson, GS; Jotte, R; Medve, R; Ramanathan, RK; Rosen, LS; Schroeder, K; Tibes, R; Von Hoff, DD; Weiss, GJ; White, E, 2013) | 0.39 |
| Excerpt | Reference | Relevance |
|---|---|---|
| " Etirinotecan pegol administration resulted in sustained and controlled systemic exposure to SN-38, which had a mean half-life of approximately 50 days." | ( A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Alemany, C; Anthony, S; Basche, M; Borad, MJ; Cohn, A; Eldon, MA; Hamm, JT; Hinshaw, I; Hoch, U; Jameson, GS; Jotte, R; Medve, R; Ramanathan, RK; Rosen, LS; Schroeder, K; Tibes, R; Von Hoff, DD; Weiss, GJ; White, E, 2013) | 0.39 |
| " The objective of this study was to develop a population pharmacokinetic (popPK) model of EP and four of its metabolites (irinotecan, SN38, SN38-glucuronide, and APC) and determine covariates affecting their pharmacokinetics." | ( Integrated population pharmacokinetics of etirinotecan pegol and its four metabolites in cancer patients with solid tumors. Chia, YL; Eldon, MA; Gordi, T; Hoch, U; Sy, SKB, 2018) | 0.48 |
This randomized phase II trial investigated two dosing schedules of etirinotecan pegol in patients with platinum-resistant/refractory ovarian carcinoma.
| Timeframe | Studies, This Drug (%) | All Drugs % |
|---|---|---|
| pre-1990 | 0 (0.00) | 18.7374 |
| 1990's | 0 (0.00) | 18.2507 |
| 2000's | 0 (0.00) | 29.6817 |
| 2010's | 15 (83.33) | 24.3611 |
| 2020's | 3 (16.67) | 2.80 |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Publication Type | This drug (%) | All Drugs (%) |
|---|---|---|
| Trials | 10 (55.56%) | 5.53% |
| Reviews | 2 (11.11%) | 6.00% |
| Case Studies | 0 (0.00%) | 4.05% |
| Observational | 0 (0.00%) | 0.25% |
| Other | 6 (33.33%) | 84.16% |
| [information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023] | ||
| Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
|---|---|---|---|---|---|---|---|
| A Phase 2 Study of Etirinotecan Pegol (NKTR-102) in Patients With Refractory Brain Metastases and Advanced Lung Cancer or Metastatic Breast Cancer (MBC) [NCT02312622] | Phase 2 | 27 participants (Actual) | Interventional | 2015-08-31 | Completed | ||
| A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Platinum-Resistant Ovarian Cancer [NCT00806156] | Phase 2 | 178 participants (Actual) | Interventional | 2008-10-31 | Completed | ||
| A Multicenter, Open-Label, Randomized, Phase 2 Study to Evaluate the Efficacy and Safety of NKTR-102 Versus Irinotecan in Patients With Second-Line, Irinotecan-Naive, KRAS-Mutant, Metastatic Colorectal Cancer (mCRC) [NCT00856375] | Phase 2 | 83 participants (Actual) | Interventional | 2008-12-31 | Completed | ||
| A Multicenter, Open-Label, Phase 2 Study to Evaluate the Safety and Efficacy of NKTR-102 When Given on a Q14 Day or a Q21 Day Schedule in Patients With Metastatic or Locally Advanced Breast Cancer Whose Disease Has Failed Prior Taxane-Based Treatment [NCT00802945] | Phase 2 | 70 participants (Actual) | Interventional | 2008-10-31 | Completed | ||
| A Phase 1 Study to Evaluate the Effect of Nktr-102 for Injection (Etirinotecan Pegol) on the QT/QTC Interval in Patients With Advanced or Metastatic Solid Tumors [NCT01976143] | Phase 1 | 33 participants (Actual) | Interventional | 2014-02-28 | Completed | ||
| An Open-Label, Parallel-Group, Multicenter, Phase 1 Study to Investigate the Pharmacokinetics of NKTR-102 for Injection (Etirinotecan Pegol) in Patients With Advanced or Metastatic Solid Tumors and Hepatic Impairment [NCT01991678] | Phase 1 | 25 participants (Actual) | Interventional | 2013-11-30 | Completed | ||
| A Multicenter, Open-Label, Phase 2 Study to Determine the Dose, Safety and Efficacy of NKTR-102 (PEG-Irinotecan) in Combination With Cetuximab in Patients With Solid Tumors Refractory to Standard Treatment and to Evaluate the Safety and Efficacy of NKTR-1 [NCT00598975] | Phase 2 | 18 participants (Actual) | Interventional | 2008-02-29 | Completed | ||
| The BEACON Study (Breast Cancer Outcomes With NKTR-102): A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Locally Recurrent or Metastatic Breast Cancer Previously Treated With an [NCT01492101] | Phase 3 | 852 participants (Actual) | Interventional | 2011-12-31 | Completed | ||
| An Open-Label, Multicenter, Extension Study of NKTR-102 in Subjects Previously Enrolled in NKTR-102 Studies [NCT01457118] | Phase 2 | 27 participants (Actual) | Interventional | 2011-10-31 | Completed | ||
| A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and C [NCT02915744] | Phase 3 | 178 participants (Actual) | Interventional | 2016-11-30 | Completed | ||
| Phase 2 Study of Etirinotecan Pegol (NKTR-102) in the Treatment of Patients With Metastatic and Recurrent Non-Small Cell Lung Cancer (NSCLC) After Failure of 2nd Line Treatment [NCT01773109] | Phase 2 | 40 participants (Actual) | Interventional | 2013-01-31 | Completed | ||
| A Phase II, Single Arm, Open Label Study Of NKTR-102 In Bevacizumab-Resistant High Grade Glioma [NCT01663012] | Phase 2 | 20 participants (Actual) | Interventional | 2012-07-31 | Completed | ||
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] | |||||||
Complete Response is defined as the disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. The best overall response was the best response recorded from the start of the study drug until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). (NCT00598975)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) | |||
|---|---|---|---|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | |
| NKTR-102 100 mg/m2 + Cetuximab | 0 | 3 | 2 | 7 |
| NKTR-102 125 mg/m2 + Cetuximab | 0 | 0 | 3 | 1 |
| Total | 0 | 3 | 5 | 8 |
Number of patients with Dose Limiting Toxicities by NCI-CTCAE (NCT00598975)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) | |||||
|---|---|---|---|---|---|---|
| Dehydration : Any grade | Dehydration : Grade 3 | Diarrhoea : Any grade | Diarrhoea : Grade 3 | Renal Failure Acute : Any grade | Renal Failure Acute : Grade 4 | |
| NKTR-102 100 mg/m2 + Cetuximab | 0 | 0 | 1 | 1 | 0 | 0 |
| NKTR-102 125 mg/m2 + Cetuximab | 1 | 1 | 1 | 1 | 1 | 1 |
| Total | 1 | 1 | 2 | 2 | 1 | 1 |
Number of patients with Dose Limiting Toxicities (NCT00598975)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Dehydration | Diarrhoea | Renal Failure Acute | |
| NKTR-102 100 mg/m2 + Cetuximab | 0 | 1 | 0 |
| NKTR-102 125 mg/m2 + Cetuximab | 1 | 1 | 1 |
| Total | 1 | 2 | 1 |
Per Response Evaluation Criteria In Solid Tumors (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00802945)
Timeframe: Up to 2 years.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 14 Day | 28.6 |
| NKTR-102 21 Days | 35 |
"Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 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, or similar definition as accurate and appropriate." (NCT00802945)
Timeframe: Up to 2 years.
| Intervention | Months (Median) |
|---|---|
| NKTR-102 14 Day | 3.3 |
| NKTR-102 21 Days | 5.6 |
Six-month survival (i.e., overall survival proportion at 6 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population. (NCT00802945)
Timeframe: From Cycle 1 Day 1 to the end of 6 months.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 14 Day | 57.1 |
| NKTR-102 21 Days | 82.9 |
One year survival (i.e., overall survival proportion at 12 months) was estimated using Kaplan Meier method. The analyses were performed in the ITT population. (NCT00802945)
Timeframe: From Cycle 1 Day 1 to the end of 12 months.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 14 Day | 42.9 |
| NKTR-102 21 Days | 51.4 |
OS was calculated as the time from the date of first study drug administration until death from any cause. Subjects alive at the time of analysis were censored at the time they were last known alive. OS was analyzed for the ITT population. (NCT00802945)
Timeframe: Up to 2 years.
| Intervention | Months (Median) |
|---|---|
| NKTR-102 14 Day | 8.8 |
| NKTR-102 21 Days | 13.1 |
An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not thought to be related to the investigational product. TEAE was any event not present before exposure to the study drug or any event already present that worsened in either intensity or frequency after exposure to the study drug. All AEs were assessed for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life threatening or disabling; Grade 5 = Death. (NCT00802945)
Timeframe: Up to 2 years.
| Intervention | percentage of subjects (Number) | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Percentage of Patient with at Least 1 TEAE | Diarrhoea | Nausea | Fatigue | Vomiting | Decreased appetite | Abdominal pain | Dehydration | Neutropenia | Anaemia | Dyspnoea | Disease progression | Lethargy | Dizziness | |
| NKTR-102 14 Day | 68.6 | 20.0 | 5.7 | 14.3 | 8.6 | 2.9 | 2.9 | 8.6 | 11.4 | 2.9 | 2.9 | 14.3 | 2.9 | 2.9 |
| NKTR-102 21 Days | 54.3 | 22.9 | 2.9 | 8.6 | 5.7 | 0 | 0 | 11.4 | 11.4 | 2.9 | 0 | 8.6 | 0 | 2.9 |
The ORR was defined as the proportion of patients with a complete response (CR) or a partial response (PR) per RECIST 1.0 based upon the best response as assessed by the Investigator. CR was defined by RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm. PR was defined by RECIST 1.1 as at least a 30% decrease in the sum of the diameters (SOD) of target lesions, taking as reference the baseline SOD. The analysis was performed for patients in the Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q21d | 14.4 |
| Primary Efficacy Population | 14.4 |
According to enhanced RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR an unambiguous increase in the sum of target lesion volumes with both 1) >20% increase in the sum of volumes (SOV) of all target lesions (taking as reference the nadir) and 2) greater than two times the variability of the measurements estimated by the sponsor and/or its designees. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 4.1 |
| NKTR-102 q21d | 4.4 |
| MITT Population | 4.4 |
The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the MITT Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 21.6 |
| NKTR-102 q21d | 15.2 |
| MITT Population | 16.6 |
The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 15.4 |
| NKTR-102 q21d | 15.4 |
| Platinum-Refractory Population | 15.4 |
The ORR was defined as the proportion of patients with a CR or a PR per RECIST 1.0 based upon the best response as assessed by the Investigator assessment. The analysis was performed for patients in the PLD Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 18.8 |
| NKTR-102 q21d | 14.9 |
| Prior PLD Population | 15.4 |
PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 11.9 |
| NKTR-102 q21d | 2.7 |
| Platinum-Refractory Population | 3 |
Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 61.5 |
| NKTR-102 q21d | 38.5 |
| Platinum-Refractory Population | 43.1 |
"Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment. Analysis was performed in Platinum-Refractory Population." (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 23.1 |
| NKTR-102 q21d | 17.3 |
| Platinum-Refractory Population | 18.5 |
"Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment. Analysis was performed in Primary Efficacy Population." (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q21d | 25 |
| Primary Efficacy Population | 25 |
"Best overall response was defined as the proportion of patients with a CR or a PR per assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and CA-125 criteria. A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the ULN and within 2 weeks prior to starting treatment. Analysis was performed in Prior PLD Therapy Population." (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 25 |
| NKTR-102 q21d | 24.6 |
| Prior PLD Population | 24.6 |
"Best overall response was defined as the proportion of patients with a CR or a PR as assessed per GCIG criteria. The GCIG proposed the following definition for the date of progression which used both the RECIST and cancer antigen 125 (CA-125) criteria. A response according to CA-125 has occurred if there is ≥ 50% reduction in CA-125 levels from a pretreatment sample. The response had to be confirmed and maintained for at least 28 days. Patients can be evaluated according to CA-125 only if they had a pretreatment sample that was at least twice the upper limit of normal (ULN) and within 2 weeks prior to starting treatment. Analysis was performed in MITT Population." (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 29.7 |
| NKTR-102 q21d | 25 |
| MITT Population | 26 |
CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in MITT Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 43.8 |
| NKTR-102 q21d | 34.9 |
| MITT Population | 36.9 |
CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 36.4 |
| NKTR-102 q21d | 20 |
| Platinum-Refractory Population | 23.5 |
CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q21d | 33 |
| Primary Efficacy Population | 33 |
CA-125 response was determined by having achieved a ≥50% reduction in serum levels of CA-125 from a pre-treatment level of at least twice the ULN within 2 weeks of starting treatment according to the GCIG criteria. The CA-125 response rate was calculated as the number of patients meeting the endpoint definition divided by the total number of eligible patients per the GCIG criteria for CA-125 in the analysis population. Analysis was performed in Prior PLD Therapy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 40 |
| NKTR-102 q21d | 33.7 |
| Prior PLD Population | 34.5 |
Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in MITT Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 56.8 |
| NKTR-102 q21d | 50.8 |
| MITT Population | 52.1 |
Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q21d | 51 |
| Primary Efficacy Population | 51 |
Clinical benefit rate was calculated as the number of patients with confirmed CR, PR, or SD (where the duration of SD should be ≥ 3 months) by RECIST divided by the total number of measurable patients in the population. Analysis was performed in Prior PLD Therapy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Percentage of Patients (Number) |
|---|---|
| NKTR-102 q14d | 56.3 |
| NKTR-102 q21d | 50.9 |
| Prior PLD Population | 51.5 |
DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 10.8 |
| NKTR-102 q21d | 7.4 |
| Platinum-Refractory Population | 7.4 |
DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q21d | 7.4 |
| Primary Efficacy Population | 7.4 |
DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in Prior PLD Therapy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 4.2 |
| NKTR-102 q21d | 7.4 |
| Prior PLD Population | 6.6 |
DoR was defined as the time from the first documented CR or PR, the date of PD (assessed by central radiological review according to RECIST), or death due to any cause, whichever came first. Patients who were alive without documented PD per RECIST were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease, whichever was earlier. Analysis was performed in MITT Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 4.1 |
| NKTR-102 q21d | 6.6 |
| MITT Population | 5.7 |
Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Platinum-Refractory Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 11.1 |
| NKTR-102 q21d | 8 |
| Platinum-Refractory Population | 9.4 |
Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q21d | 10.9 |
| Primary Efficacy Population | 10.9 |
Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in Prior PLD Therapy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 12.2 |
| NKTR-102 q21d | 11 |
| Prior PLD Population | 11 |
Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. Analysis was performed in MITT Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 11.1 |
| NKTR-102 q21d | 10.2 |
| MITT Population | 10.6 |
PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Primary Efficacy Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q21d | 4.4 |
| Primary Efficacy Population | 4.4 |
PFS was defined as the time from the date of the first NKTR-102 administration to the date of PD or death due to any cause. Progressive disease was determined by Investigators using RECIST criteria. Patients who were alive without disease progression at the time of data-cut-off were censored at the time of the last tumor assessment that demonstrated a lack of disease progression (or on Cycle 1 Day 1 if the patient did not undergo repeated imaging while on study). Analysis was performed in Prior PLD Population. (NCT00806156)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study (approximately 3 years and 11 months)
| Intervention | Months (Median) |
|---|---|
| NKTR-102 q14d | 5.5 |
| NKTR-102 q21d | 4.4 |
| Prior PLD Population | 4.5 |
An adverse event (AE) was any untoward medical occurrence in a patient administered a pharmaceutical product which did not necessarily have a causal relationship with the treatment. An AE could have been any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing events, which increased in frequency or severity or changed in nature during or as a consequence of use of the study medication were also considered as AEs. All AEs were assessed for severity using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 3.0. If a particular AE was not listed in the NCI CTCAE Version 3.0, the following criteria were used: Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. (NCT00856375)
Timeframe: From the first dose of study medication through the End-of-Treatment visit (30 ± 3 days from last dose of study drug), assessed until the end of study approximately 42 months
| Intervention | % of participants (Number) | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Percentage of participants with ≥1 TEAE | Percentage of participants with Diarrhea | Percentage of participants with Neutropenia | Percentage of participants with Abdominal Pain | Percentage of participants with Dehydration | Percentage of participants with Vomiting | Percentage of participants with Nausea | Percentage of participants with Hypokalemia | Percentage of participants with Fatigue | Percentage of participants with Intestinal Obstruction | Percentage of participants with Leukopenia | Percentage of participants with Febrile Neutropenia | Percentage of participants with Alopecia | Percentage of participants with Disease Progression | Percentage of participants with Hyponatremia | Percentage of participants with Acute Prerenal Failure | Percentage of participants with Asthenia | Percentage of participants with Hyperbilirubinemia | Percentage of participants with Performance Status Decreased | Percentage of participants with Sepsis | |
| Irinotecan | 63.9 | 19.5 | 14.6 | 4.9 | 9.8 | 7.3 | 2.4 | 7.3 | 2.4 | 9.8 | 4.9 | 7.3 | 4.9 | 2.4 | 4.9 | 2.4 | 2.4 | 2.4 | 0 | 4.9 |
| NKTR-102 | 61.9 | 21.4 | 7.1 | 14.3 | 9.5 | 11.9 | 14.3 | 7.1 | 9.5 | 2.4 | 7.1 | 2.4 | 2.4 | 4.8 | 2.4 | 2.4 | 2.4 | 2.4 | 4.8 | 0 |
ORR was defined as the proportion of patients with a complete response (CR) or a partial response (PR) per RECIST 1.1 based upon the best response as assessed by central radiological review; confirmation of response was not required. The analyses were performed for patients in the ITT population who had measurable disease as determined by the central imaging facility at baseline. (NCT00856375)
Timeframe: From randomization of the first subject until documented disease progression, start of new therapy for cancer, death, or end of study approximately 42 months
| Intervention | percentage of patients (Median) |
|---|---|
| NKTR-102 | 9.8 |
| Irinotecan | 5.0 |
PFS was defined as the time from the date of randomisation to the date of disease progression (assessed by central radiological review according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or death due to any cause, whichever comes first. PFS was determined using the intention-to-treat (ITT) population which included all randomized patients who underwent baseline evaluation, with treatment assigned according to randomized arm. For patients whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For patients who received new anti-cancer therapy, the PFS time was censored at the time of last tumor assessment prior to the new anti-cancer therapy starts. (NCT00856375)
Timeframe: Every 6 weeks (± 5 days) from Cycle 1, Day 1 until documented disease progression, start of new therapy for cancer, death, or end of study, approximately 42 months.
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 4.0 |
| Irinotecan | 2.8 |
Duration of OS was defined as the time from the date of randomization to the date of death due to any cause. Patients were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. Patients who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Patients who did not have any follow-up since the date of randomization were censored at the date of randomization. (NCT00856375)
Timeframe: From randomization to death, loss to follow-up, withdrawal of consent for further follow-up for survival, or end of study, approximately 42 months.
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 9.6 |
| Irinotecan | 8.4 |
Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that was the smallest on study); in addition to a relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. CR is defined as disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (NCT00856375)
Timeframe: From the time measurement criteria for CR/PR (whichever was first recorded) were first met until the first date that recurrent disease or PD or death was objectively documented, assessed until the end of study approximately 42 months
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 7.9 |
| Irinotecan | 1.4 |
To provide access to NKTR-102 to subjects who previously received NKTR-102 in a clinical trial and were without signs of disease progression since receiving NKTR-102. (NCT01457118)
Timeframe: Screening, Every 21 day cycle of treatment and Quarterly Follow-up
| Intervention | days (Mean) |
|---|---|
| 145 mg/m2 | 139.0 |
| 120 mg/m2 | 33.0 |
| 95 mg/m2 | 126.0 |
| 50 mg/m2 | 21.0 |
To evaluate the safety of continued exposure to NKTR-102. (NCT01457118)
Timeframe: Screening, Every 21 day cycle of treatment and Quarterly Follow-up
| Intervention | # of events (Number) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| # of Subjects with Anemia | # of Subjects with Neutropenia | # of Subjects with Leukopenia | # of Subjects with Tachycardia | # of Subjects with Vision Blurred | # of Subjects with Photophobia | # of Subjects with Diarrhea | # of Subjects with Nausea | # of Subjects with Vomiting | # of Subjects with Constipation | # of Subjects with Abdominal Pain | # of Subjects with Dyspepsia | # of Subjects with Upper Abdominal Pain | # of Subjects with Ascites | # of Subjects with Dry Mouth | # of Subjects with Hypoaesthesia Oral | # of Subjects with Mouth Ulceration | # of Subjects with Stomatitis | # of Subjects with Fatigue | # of Subjects with Oedema Peripheral | # of Subjects with Non-Cardiac Chest Pain | # of Subjects with Pyrexia | # of Subjects with Urinary Tract Infections | # of Subjects with Gastroenteritis | # of Subjects with Influenza | # of Subjects with Abdominal Infection | # of Subjects with Gingival Infection | # of Subjects with Herpex Simplex Encephalitis | # of Subjects with Weight Decreased | # of Subjects with Neutrophil Count Decreased | # of Subjects with Aspartate Aminostransferase | # of Subjects with White blood cell count decreased | # of Subjects with Activated partial thromboplastin time prolonged | # of Subjects with Alanine Aminotransferase Increased | # of Subjects with Blood bilirubin increased | # of Subjects with Blood creatine increased | # of Subjects with Liver Function Test abnormal | # of Subjects with Prothrombin time prolonged | # of Subjects with decreased appetite | # of Subjects with hypoalbuminemia | # of Subjects with hypokalemia | # of Subjects with hypoglycemia | # of Subjects with hyponatremia | # of Subjects with dehydration | # of Subjects with Hyperglycemia | # of Subjects with Hypocalcemia | # of Subjects with Hypomagnesemia | # of Subjects with Hypophosphatemia | # of Subjects with Back Pain | # of Subjects with Flank Pain | # of Subjects with Muscular Weakness | # of Subjects with Musculoskeletal Pain | # of Subjects with Appendix Cancer | # of Subjects with Cancer Pain | # of Subjects with Aphonia | # of Subjects with Dyasgeusia | # of Subjects with Hypoaesthsia | # of Subjects with Depressed Mood | # of Subjects with Insomnia | # of Subjects with Proteinuria | # of Subjects with Renal Failure Acute | # of Subjects with Vaginal Hemorrhage | # of Subjects with Oropharyngeal Pain | # of Subjects with Cough | # of Subjects with Dsypnoea | # of Subjects with Epistaxis | # of Subjects with Hypoxis | # of Subjects with Pneumothorax | # of Subjects with Productive Cough | # of Subjects with Pulmonary Embolism | # of Subjects with Decubitus Ulcer | # of Subjects with Pruritus | # of Subjects with Rash | # of Subjects with Alopecia | # of Subjects with Hypotension | # of Subjects with Pelvic Venous Thrombosis | Number of Subjects with at least one TEAE | # of Subjects with Peritonitis Bacterial | |
| 120 mg/m2 | 1 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 1 |
| 145 mg/m2 | 3 | 3 | 1 | 1 | 3 | 1 | 11 | 6 | 4 | 4 | 2 | 2 | 1 | 0 | 0 | 1 | 1 | 1 | 6 | 2 | 1 | 1 | 3 | 1 | 0 | 0 | 1 | 0 | 5 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 4 | 3 | 2 | 1 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 20 | 0 |
| 50 mg/m2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 0 |
| 95 mg/m2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
To evaluate the efficacy of NKTR-102 in subjects with advanced or metastatic solid tumors. (NCT01457118)
Timeframe: Screening, Every 21 day cycle of treatment and Quarterly Follow-up
| Intervention | participants (Number) | |
|---|---|---|
| # of Participants who achieved Complete Response (CR) | # of Participants who achieved Partial Response (PR) | |
| 120 mg/m2 | 0 | 0 |
| 145 mg/m2 | 0 | 0 |
| 95 mg/m2 | 0 | 0 |
CBR was defined as the proportion of subjects with a CR, PR, or stable disease (SD) for at least 6 months (≥ 182 days). (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 | 20.5 |
| Physician's Treatment of Choice | 19.6 |
DOR was defined as the time from first documented CR or PR until the earliest evidence of disease progression or death from any cause. Subjects who were alive without documented disease progression per RECIST version 1.1 were censored at the date of last tumor assessment without disease progression or start of new anti-cancer therapy for the study disease. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | Months (Median) |
|---|---|
| NKTR-102 | 3.9 |
| Physician's Treatment of Choice | 3.7 |
Proportion of subjects who had a reduction in dose. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 | 27.5 |
| Physician's Treatment of Choice | 28.3 |
Duration of OS was defined as the time from the date of randomisation to the date of death due to any cause. Subjects were followed until their date of death, loss to follow-up, withdrawal of consent for further follow-up for survival, or final database closure. OS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. Subjects who were lost-to-follow-up or were not known to have died were censored at last date they were shown to be alive. Subjects who did not have any follow-up since the date of randomization were censored at the date of randomization. (NCT01492101)
Timeframe: 36 Months
| Intervention | Months (Median) |
|---|---|
| NKTR-102 | 12.4 |
| Physician's Treatment of Choice | 10.3 |
PFS was defined as the time from the date of randomization to the earliest date of disease progression (assessed by the investigator according to RECIST version 1.1) or death due to any cause. PFS was determined using the ITT population which included all subjects randomized into 1 of the 2 treatment arms. For subjects whose disease did not progress or who did not die, the PFS time was censored at the time of the last tumor assessment that demonstrated lack of disease progression. For subjects who received new anti-cancer therapy, the PFS time was censored at the start of the new anti-cancer therapy. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | Months (Median) |
|---|---|
| NKTR-102 | 2.4 |
| Physician's Treatment of Choice | 2.8 |
ORR was defined as the proportion of subjects with a complete response (CR) or a partial response (PR), assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 The analyses were performed for subjects in the efficacy evaluable population who had measurable disease as determined by the investigator at baseline. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | percentage of subjects (Number) |
|---|---|
| NKTR-102 | 16.4 |
| Physician's Treatment of Choice | 17.0 |
Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean t½ values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. The t½ of all analytes was primarily driven by NKTR-102. Thus, the NKTR-102 t½ of 37 days also applies to all NKTR-102 metabolites. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | days (Mean) |
|---|---|
| NKTR-102 | 36.8 |
"The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms." (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | units on a scale (Mean) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Body image: Week 8 | Body image: Week 16 | Body image: Week 24 | Body image: Week 32 | Body image: Week 40 | Body image: Week 48 | Body image: Week 56 | Sexual functioning: Week 8 | Sexual functioning: Week 16 | Sexual functioning: Week 24 | Sexual functioning: Week 32 | Sexual functioning: Week 40 | Sexual functioning: Week 48 | Sexual functioning: Week 56 | Sexual enjoyment: Week 8 | Sexual enjoyment: Week 16 | Sexual enjoyment: Week 24 | Sexual enjoyment: Week 32 | Sexual enjoyment: Week 40 | Sexual enjoyment: Week 48 | Sexual enjoyment: Week 56 | Future perspective: Week 8 | Future perspective: Week 16 | Future perspective: Week 24 | Future perspective: Week 32 | Future perspective: Week 40 | Future perspective: Week 48 | Future perspective: Week 56 | Systemic therapy side effects: Week 8 | Systemic therapy side effects: Week 16 | Systemic therapy side effects: Week 24 | Systemic therapy side effects: Week 32 | Systemic therapy side effects: Week 40 | Systemic therapy side effects: Week 48 | Systemic therapy side effects: Week 56 | Breast symptoms: Week 8 | Breast symptoms: Week 16 | Breast symptoms: Week 24 | Breast symptoms: Week 32 | Breast symptoms: Week 40 | Breast symptoms: Week 48 | Breast symptoms: Week 56 | Arm symptoms: Week 8 | Arm symptoms: Week 16 | Arm symptoms: Week 24 | Arm symptoms: Week 32 | Arm symptoms: Week 40 | Arm symptoms: Week 48 | Arm symptoms: Week 56 | Upset by hair loss: Week 8 | Upset by hair loss: Week 16 | Upset by hair loss: Week 24 | Upset by hair loss: Week 32 | Upset by hair loss: Week 40 | Upset by hair loss: Week 48 | Upset by hair loss: Week 56 | |
| NKTR-102 | -0.8 | -0.8 | 0.8 | -1.2 | 3.3 | -0.3 | 3.9 | -0.8 | 0.1 | -2.8 | -2.2 | -5.4 | -9.6 | -5.3 | 2.6 | -0.3 | 1.9 | 2.0 | -15.3 | -27.8 | -9.8 | 3.5 | 6.9 | 9.3 | 6.1 | 7.1 | 9.2 | 16.0 | 2.3 | 3.0 | 2.2 | 3.5 | 3.2 | 0.3 | -1.1 | -1.7 | -3.5 | -4.8 | -2.5 | -1.9 | -2.7 | -3.4 | -3.0 | -5.1 | -4.9 | -4.4 | -6.0 | -5.6 | -5.6 | -4.7 | 8.3 | 6.8 | 6.9 | -4.2 | -16.7 | -14.6 |
| Physician's Treatment of Choice | -2.2 | -2.3 | -4.7 | -0.3 | -2.4 | -1.1 | -10.2 | -2.2 | -0.8 | -1.4 | -.7 | 2.7 | 1.6 | 1.7 | -4.2 | -8.6 | -3.5 | -2.6 | 7.1 | 6.7 | 0 | 1.5 | 3.6 | 6.6 | 4.4 | 13.3 | 6.1 | -3.1 | 7.9 | 9.1 | 6.9 | 7.3 | 10.1 | 6.4 | 6.8 | -0.2 | 0.1 | -1.1 | -2.8 | -0.2 | 0 | 2.5 | -0.9 | 1.1 | -0.3 | -0.5 | 5.2 | -1.4 | -1.4 | 0.1 | 2.9 | 3.5 | -2.3 | 20.2 | 21.7 | 16.7 |
Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population pharmacokinetic (PK) model-derived mean AUC values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | μg·h/mL (Mean) | ||||
|---|---|---|---|---|---|
| NKTR-102 | Irinotecan | SN38 | SN38G | APC | |
| NKTR-102 | 4619 | 18.8 | 5.32 | 40.6 | 4.0 |
"The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhea, constipation, insomnia and dyspnea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (from 1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms." (NCT01492101)
Timeframe: From Baseline to Week 8, Week 16, Week 24, Week 32, Week 40, Week 48, Week 56.
| Intervention | units on a scale (Mean) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Global health status/QoL: Week 8 | Global health status/QoL: Week 16 | Global health status/QoL: Week 24 | Global health status/QoL: Week 32 | Global health status/QoL: Week 40 | Global health status/QoL: Week 48 | Global health status/QoL: Week 56 | Physical functioning: Week 8 | Physical functioning: Week 16 | Physical functioning: Week 24 | Physical functioning: Week 32 | Physical functioning: Week 40 | Physical functioning: Week 48 | Physical functioning: Week 56 | Role functioning: Week 8 | Role functioning: Week 16 | Role functioning: Week 24 | Role functioning: Week 32 | Role functioning: Week 40 | Role functioning: Week 48 | Role functioning: Week 56 | Emotional functioning: Week 8 | Emotional functioning: Week 16 | Emotional functioning: Week 24 | Emotional functioning: Week 32 | Emotional functioning: Week 40 | Emotional functioning: Week 48 | Emotional functioning: Week 56 | Cognitive functioning: Week 8 | Cognitive functioning: Week 16 | Cognitive functioning: Week 24 | Cognitive functioning: Week 32 | Cognitive functioning: Week 40 | Cognitive functioning: Week 48 | Cognitive functioning: Week 56 | Social functioning: Week 8 | Social functioning: Week 16 | Social functioning: Week 24 | Social functioning: Week 32 | Social functioning: Week 40 | Social functioning: Week 48 | Social functioning: Week 56 | Fatigue: Week 8 | Fatigue: Week 16 | Fatigue: Week 24 | Fatigue: Week 32 | Fatigue: Week 40 | Fatigue: Week 48 | Fatigue: Week 56 | Nausea and vomiting: Week 8 | Nausea and vomiting: Week 16 | Nausea and vomiting: Week 24 | Nausea and vomiting: Week 32 | Nausea and vomiting: Week 40 | Nausea and vomiting: Week 48 | Nausea and vomiting: Week 56 | Pain: Week 8 | Pain: Week 16 | Pain: Week 24 | Pain: Week 32 | Pain: Week 40 | Pain: Week 48 | Pain: Week 56 | Dyspnoea: Week 8 | Dyspnoea: Week 16 | Dyspnoea: Week 24 | Dyspnoea: Week 32 | Dyspnoea: Week 40 | Dyspnoea: Week 48 | Dyspnoea: Week 56 | Insomnia: Week 8 | Insomnia: Week 16 | Insomnia: Week 24 | Insomnia: Week 32 | Insomnia: Week 40 | Insomnia: Week 48 | Insomnia: Week 56 | Appetite loss: Week 8 | Appetite loss: Week 16 | Appetite loss: Week 24 | Appetite loss: Week 32 | Appetite loss: Week 40 | Appetite loss: Week 48 | Appetite loss: Week 56 | Constipation: Week 8 | Constipation: Week 16 | Constipation: Week 24 | Constipation: Week 32 | Constipation: Week 40 | Constipation: Week 48 | Constipation: Week 56 | Diarrhoea: Week 8 | Diarrhoea: Week 16 | Diarrhoea: Week 24 | Diarrhoea: Week 32 | Diarrhoea: Week 40 | Diarrhoea: Week 48 | Diarrhoea: Week 56 | Financial difficulties: Week 8 | Financial difficulties: Week 16 | Financial difficulties: Week 24 | Financial difficulties: Week 32 | Financial difficulties: Week 40 | Financial difficulties: Week 48 | Financial difficulties: Week 56 | |
| NKTR-102 | -4.4 | -2.5 | -1.8 | -0.2 | -5.2 | -2.3 | 2.9 | -4.9 | -3.0 | 0.3 | -3.0 | -1.9 | 0.2 | 2.2 | -6.6 | -4.8 | -7.8 | -9.7 | -8.7 | -3.1 | -2.6 | -0.5 | 2.7 | -0.6 | -2.8 | -1.4 | 0.9 | -3.6 | -3.3 | -1.4 | -1.8 | -4.6 | -5.7 | -4.6 | -2.9 | -4.9 | 0.4 | -3.4 | -8.8 | -9.7 | -5.5 | -3.2 | 6.7 | 3.7 | 3.0 | 5.0 | 4.1 | 0.9 | 2.1 | 12.8 | 8.8 | 7.2 | 6.5 | 4.5 | 5.0 | 8.0 | -1.7 | -5.0 | -4.1 | -1.0 | 1.6 | -0.8 | -4.2 | 0.7 | -1.1 | -2.0 | 0 | 2.4 | -5.6 | -7.1 | -1.5 | -1.4 | -2.7 | 1.5 | 0 | 2.8 | -1.3 | 11.6 | 9.4 | 4.6 | 8.9 | 6.9 | 2.2 | 14.7 | 2.1 | 0.2 | 0.5 | 4.6 | 1.0 | -0.6 | 1.9 | 10.2 | 10.8 | 9.4 | 9.2 | 8.3 | 12.1 | 4.5 | -0.7 | 0.8 | 1.0 | 1.2 | 4.2 | 0 | -1.9 |
| Physician's Treatment of Choice | -4.7 | -5.6 | -6.6 | -6.3 | -2.6 | -1.8 | -11.1 | -7.1 | -7.0 | -4.7 | -8.5 | -6.4 | -7.4 | -10.4 | -8.3 | -8.3 | -10.8 | -12.2 | -7.8 | -5.7 | -9.4 | -2.0 | -1.6 | -3.7 | -7.6 | 0.8 | 1.2 | -4.7 | -3.2 | -4.4 | -2.2 | -7.9 | -3.5 | 2.2 | -6.7 | -6.2 | -6.4 | -7.2 | -7.2 | -7.0 | -6.6 | -24.4 | 6.6 | 7.7 | 3.6 | 6.6 | 2.3 | 6.7 | 4.5 | 4.2 | -2.0 | -0.1 | 3.5 | 5.6 | 3.9 | 1.6 | 2.4 | 1.9 | 2.1 | 3.9 | 1.3 | -0.4 | 0.5 | 5.8 | 4.6 | 1.4 | 8.6 | 5.0 | -0.9 | -1.2 | 3.3 | 2.1 | 1.3 | 2.5 | 4.4 | 0.9 | -1.0 | 4.0 | -2.1 | -1.6 | 0 | 5.4 | 13.0 | 1.0 | 6.7 | 3.1 | -2.0 | 0.3 | -3.2 | 7.0 | -4.4 | 1.8 | 3.4 | 2.4 | 0.8 | 7.8 | 0 | 6.7 | 0.6 | 1.0 | 4.6 | 10.2 | -1.7 | 3.5 | 5.6 |
"The QLQ-BR23 incorporates 5 multi-item scales to assess systemic therapy side effects, arm symptoms, breast symptoms, body image and sexual functioning, and 3 single items to assess sexual enjoyment, upset by hair loss and future perspective. Most items were scaled one to four except the items contributing to the global health status/QoL, which were seven-point questions. Raw scores were transformed using a linear transformation to standardize the results so that scores ranged from 0-100. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms." (NCT01492101)
Timeframe: Baseline
| Intervention | units on a scale (Mean) | |||||||
|---|---|---|---|---|---|---|---|---|
| Body image | Sexual functioning | Sexual enjoyment | Future perspective | Systemic therapy side effects | Breast symptoms | Arm symptoms | Upset by hair loss | |
| NKTR-102 | 69.5 | 14.1 | 36.1 | 38.7 | 21.9 | 15.3 | 20.8 | 33.2 |
| Physician's Treatment of Choice | 69.9 | 13.3 | 34.2 | 36.1 | 22.3 | 15.8 | 22.2 | 30.5 |
"The QLQ-C30 is composed of 5 multi-item functional scales (physical, role, social, emotional and cognitive functioning), a global health status/QoL scale, 3 symptom scales (fatigue, nausea/vomiting, and pain), and 6 single items (financial impact, appetite loss, diarrhoea, constipation, insomnia and dyspnoea). Most items are scaled 1 to 4 (1 = not at all, 2 = a little, 3 = quite a bit, 4 = very much) except the items contributing to the global health status/QoL, which are 7-point questions (1 = very poor to 7 = excellent). Raw scores were transformed using a linear transformation to standardize the results so that scores range from 0 to 100. n=number of subjects who completed each individual scale. Note that for scores measuring function, a higher score represented a higher better level of functioning, while for scores measuring symptoms, a higher score represented a lower worse level of symptoms." (NCT01492101)
Timeframe: Up to 39 months
| Intervention | units on a scale (Mean) | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Global health status/QoL | Physical functioning | Role functioning | Emotional functioning | Cognitive functioning | Social functioning | Fatigue | Nausea and vomiting | Pain | Dyspnoea | Insomnia | Appetite loss | Constipation | Diarrhoea | Financial difficulties | |
| NKTR-102 | 61.4 | 74.5 | 71.8 | 72.4 | 82.5 | 73.0 | 37.7 | 8.6 | 32.3 | 24.5 | 29.3 | 24.3 | 18.0 | 6.3 | 26.4 |
| Physician's Treatment of Choice | 58.0 | 72.3 | 67.3 | 71.9 | 81.2 | 71.0 | 41.3 | 9.9 | 35.3 | 23.6 | 31.5 | 26.6 | 21.0 | 5.6 | 21.9 |
Plasma concentrations of NKTR-102 and its major metabolites irinotecan, SN38, SN38G, and APC were measured using validated analytical methods. The population PK model-derived mean Cmax values were computed by integration from t = 0 (start of first dose) to 21 days after the last dose. Integration was implemented using a separate compartment defined as the amount of drug or metabolite in the central compartment divided by the model-estimated volume of distribution. (NCT01492101)
Timeframe: Up to 38 months.
| Intervention | ng/mL (Mean) | ||||
|---|---|---|---|---|---|
| NKTR-102 | Irinotecan | SN38 | SN38G | APC | |
| NKTR-102 | 62701 | 138 | 4.45 | 47.7 | 7.3 |
Will be described using Kaplan-Meier estimates. (NCT01663012)
Timeframe: From date of first dose of NKTR-102 to date of death, assessed up to 2 years
| Intervention | Months (Median) |
|---|---|
| Drug: Etirinotecan Pegol | 4.5 |
Will be described using Kaplan-Meier estimates. (NCT01663012)
Timeframe: From date of pathologic diagnosis/confirmation of high grade glioma to date of death, assessed up to 2 years.
| Intervention | Months (Median) |
|---|---|
| Drug: Etirinotecan Pegol | 17.1 |
Will be described using Kaplan-Meier estimates. The PFS probability at 6 weeks (PFS-6week) will be estimated with an 80% power and 95% confidence intervals (80% in accord with the planned alpha level, 95% for comparability with other studies, confidence intervals based on the Greenwood formula for the variance of a survival probability). (NCT01663012)
Timeframe: 6 weeks from first administration of NKTR-102
| Intervention | participants (Number) |
|---|---|
| Drug: Etirinotecan Pegol | 11 |
The primary objective of this phase 2 trial is to estimate the objective response rate (Complete Response or Partial Response, as measured by RECIST version 1.1) for patients with metastatic or recurrent NSCLC being treated with etirinotecan pegol after failure of second-line therapy. (NCT01773109)
Timeframe: 6 weeks
| Intervention | Participants (Count of Participants) | ||
|---|---|---|---|
| Partial Response | Stable Disease | Progressive Disease | |
| Etirinotecan Pegol | 2 | 17 | 18 |
"Overall response by subject (OR) is defined as the lower assessment between the central nervous system response and the systemic response. Response is defined as either complete response (CR) or partial response (PR). The outcome is reported as the number and percentage of participants who achieve OR, a number without dispersion.~Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved~PR = ≥ 30% decrease in target lesion LD & no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved~PD = Any of: 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration~SD = Neither PR or PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 1 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 0 |
Overall survival (OS) is defined as the period remaining alive after the start of treatment. The outcome is reported as the median with full range. (NCT02312622)
Timeframe: 4 years
| Intervention | months (Median) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 7.00 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 8.49 |
Progression-free survival (PFS) is defined as the time from the date of start of treatment until disease progression or death. The outcome is reported by cohort as PFS in months, with full range. (NCT02312622)
Timeframe: Date of first dose of pegylated irinotecan NKTR 102 to date of disease progression, assessed up to 2 years
| Intervention | months (Median) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 2.66 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 1.35 |
"Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion.~Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all target lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved~PR = ≥ 30% decrease in target lesion LD and no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved~PD = Any of 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration~SD = Neither PR or PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort B - Pegylated Irinotecan to Treat SCLC | 0 |
"Systemic (ie, non-central nervous system) disease control (DC) rate by cohort is defined as the number of patients with complete response (CR) + partial response (PR) + stable disease (SD), divided by the total number of patients. The outcome will be reported as DC rate, a number without dispersion.~Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all lesions, no new lesions; pathological lymph nodes reduced in short axis to < 10 mm~PR = ≥ 30% decrease in sum of lesion diameters; no new lesions; no progression of non-target lesions~PD = Any of 20% increase in sum of lesion diameters; progression of non-target lesions; new lesions~SD = Neither CR, PR, nor PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort B - Pegylated Irinotecan to Treat SCLC | 0 |
"Systemic (ie, non-central nervous system) response rate by cohort is defined as the number of participants achieving a complete response (CR) or partial response (PR), divided by the number of participants. The outcome will be reported as a number without dispersion.~Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all target lesions, no new lesions; pathological lymph nodes reduced in short axis to < 10 mm~PR = ≥ 30% decrease in sum of lesion diameters; no new lesions; no progression of non-target lesions~PD = Any of 20% increase in sum of lesion diameters; progression of non-target lesions; new lesions~SD = Neither CR, PR, nor PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 1 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 0 |
"Systemic (ie, non-central nervous system) disease control (DC) rate by cohort is defined as the number of patients with complete response (CR) + partial response (PR) + stable disease (SD), divided by the total number of patients. The outcome will be reported as DC rate, a number without dispersion.~Response criteria are as follows. Note that any lesion < 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all lesions, no new lesions; pathological lymph nodes reduced in short axis to < 10 mm~PR = ≥ 30% decrease in sum of lesion diameters; no new lesions; no progression of non-target lesions~PD = Any of 20% increase in sum of lesion diameters; progression of non-target lesions; new lesions~SD = Neither CR, PR, nor PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 3 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 3 |
Toxicity, defined as related adverse events, is reported as the total number of events experienced by the participants in each cohort, a number without dispersion. Related is defined as meaning possibly, probably, or definitely related to the study drug. (NCT02312622)
Timeframe: Up to 2 years
| Intervention | adverse events (Number) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 70 |
| Cohort B - Pegylated Irinotecan to Treat SCLC | 40 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 68 |
"Central nervous system (CNS) disease control (DC) is defined as a complete response (CR); partial response (PR); or stable disease (SD). The outcome is reported as the number and percentage of participants who achieve DC, a number without dispersion.~Response criteria are as follows. Note that any lesion less than 10 mm in longest diameter (LD) is considered unchanged unless there is a ≥ 3 mm change in the sum of the LDs.~CR = Disappearance of all target lesions, sustained for ≥ 4 weeks with no new lesions; clinical condition stable or improved~PR = ≥ 30% decrease in target lesion LD and no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved~PD (progressive disease) = Any of 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration~SD = Neither PR or PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | Participants (Count of Participants) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 2 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 2 |
"Overall disease control (DC) rate is defined as the sum in a cohort of the numbers of participants achieving complete response (CR); partial response (PR); or stable disease (SD), divided by the number of patients in that cohort. For this outcome, overall means all body systems, not just the central nervous system (CNS). The outcome is reported as DC rate, a number without dispersion.~Response criteria are as follows. Note that any lesion <10 mm in longest diameter (LD) is considered unchanged unless there is a ≥3 mm change in the sum of the LDs.~CR = Disappearance of all target lesions, sustained for ≥4 weeks with no new lesions; clinical condition stable or improved~PR = ≥30% decrease in target lesion LD & no new lesions, sustained for ≥ 4 weeks; clinical condition stable or improved~PD = Any of: 20% increase in target lesion LD; increase in T2/FLAIR non-enhancing lesions; any new lesions; non-target progression; or clinical deterioration~SD = Neither PR or PD" (NCT02312622)
Timeframe: At 12 weeks
| Intervention | participants (Number) |
|---|---|
| Cohort A - Pegylated Irinotecan to Treat NSCLC | 2 |
| Cohort C - Pegylated Irinotecan to Treat mBC | 2 |
Duration of response (DoR) outside the CNS will be defined as the time from first documented CR or PR until the earliest evidence of disease progression per RECIST v1.1 or death from any cause. CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) 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 included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 7.4 |
| Treatment of Physician's Choice (TPC) | 3.5 |
Progression-free survival (CNS and peripheral) is defined as the time from the date of randomization to the earliest evidence of documented PD in either the CNS or peripheral (using RANO-BM) or death from any cause. The PD will be determined by both the investigator's and the central imaging facility assessments. The same statistical methods that were used for PFS and PFS-BM will be used for PFS (Overall). Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 2.1 |
| Treatment of Physician's Choice (TPC) | 1.9 |
Progression-Free Survival in Brain Metastasis (PFS-BM) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) in brain metastases or death from any cause. The PD will also be determined by the investigator's assessments. Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 3.9 |
| Treatment of Physician's Choice (TPC) | 3.3 |
Clinical Benefit Rate will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 4 months (≥ 120 days). CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) 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 included the baseline sum if that was the smallest on study). Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. (NCT02915744)
Timeframe: For at least 4 months, with an expected average of 1 year
| Intervention | participants (Number) | |||
|---|---|---|---|---|
| # of Patients who achieved Complete Response | # of Patients who achieved Partial Response | # of Patients who have Stable Disease >= 120 days | # of Patients who achieved Clinical Benefit Rate (CBR) | |
| NKTR-102 | 0 | 6 | 17 | 23 |
| Treatment of Physician's Choice (TPC) | 0 | 6 | 5 | 11 |
The Brief Fatigue Inventory scale utilizes a series of 4 questions. The first three are scored with a scale from 1-10. The fourth question has 6 six sub components each of which are scored with a scale of 1-10. For every scale, a score of 0 indicates no fatigue/interference where a score of 10 indicates as bad as you can imagine. A patient's score can range from 0 to 100 where 0 indicates the best outcome and 100 indicates the worst. (NCT02915744)
Timeframe: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
| Intervention | Units on a Scale (Mean) | |
|---|---|---|
| BFI Score at Baseline | BFI Score at End of Treatment, approximately 1 year | |
| NKTR-102 | 4.18 | 4.83 |
| Treatment of Physician's Choice (TPC) | 4.04 | 4.74 |
"The EORTC QLQ-BN20 Scale has a series of 20 questions each of which involve reporting a scale from 1-4. It is an increasing scale where a score of one indicates not at all while a score of four indicates very much. The minimum score is 20 and the maximum score is 80. The higher the score the worse the outcome." (NCT02915744)
Timeframe: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44.
| Intervention | Units on a Scale (Mean) | |
|---|---|---|
| QLQ-C30 Score at Baseline | QLQ-C30 Score at End of Treatment, approximately 1 year | |
| NKTR-102 | 57.59 | 46.97 |
| Treatment of Physician's Choice (TPC) | 52.25 | 52.38 |
The EQ-5D-5L scale is used to measure health by having a patient answer a series of questions. There are a series of 5 questions each of which is scaled from a score of 4-20 in increasing increments of 4. The scale is numbered from 0 to 100 where 100 means the beast health you can imagine and 0 means the worst health. (NCT02915744)
Timeframe: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 for NKTR-102 or 28 days for TPC] and end of Cycle 44
| Intervention | Units on a Scale (Mean) | |
|---|---|---|
| EQ-5D-5L Score at Baseline | EQ-5D-5L Score at End of Treatment, approximately 1 year | |
| NKTR-102 | 61.41 | 56.53 |
| Treatment of Physician's Choice (TPC) | 60.33 | 61.60 |
The magnitude of clinical benefit of NKTR-102 is assessed by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) (v1.0). The scale is graded 5, 4, 3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit, and grade 1 represents no clinical benefit. To determine the magnitude of clinical benefit when the median OS with the standard of treatment is ≤ 1 year, the score is derived from the Hazard Ratio (HR) of Overall Survival, overall survival gain, and QoL improvement between two treatment arms. Values reported in the data table are Overall Survival values. (NCT02915744)
Timeframe: Through study completion, within 3 years from study start
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 7.8 |
| Treatment of Physician's Choice (TPC) | 7.5 |
The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3 (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | Participants (Count of Participants) |
|---|---|
| NKTR-102 | 90 |
| Treatment of Physician's Choice (TPC) | 76 |
To compare Overall Survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician's Choice (TPC). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis. (NCT02915744)
Timeframe: Within 3 years from study start
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 7.8 |
| Treatment of Physician's Choice (TPC) | 7.5 |
Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) or of death from any cause. The date of global deterioration or symptomatic deterioration will not be used as the date of PD. The assessment of PFS outside the CNS will utilize RECIST criteria v1.1. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|---|
| NKTR-102 | 2.8 |
| Treatment of Physician's Choice (TPC) | 1.9 |
| Substance | Relationship Strength | Studies | Trials | Classes | Roles |
|---|---|---|---|---|---|
| deoxycytidine [no description available] | 4.45 | 1 | 1 | pyrimidine 2'-deoxyribonucleoside | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| camptothecin NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source | 5.32 | 4 | 1 | delta-lactone; pyranoindolizinoquinoline; quinoline alkaloid; tertiary alcohol | antineoplastic agent; EC 5.99.1.2 (DNA topoisomerase) inhibitor; genotoxin; plant metabolite |
| paclitaxel Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL). | 4.45 | 1 | 1 | taxane diterpenoid; tetracyclic diterpenoid | antineoplastic agent; human metabolite; metabolite; microtubule-stabilising agent |
| gemcitabine gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. | 4.45 | 1 | 1 | organofluorine compound; pyrimidine 2'-deoxyribonucleoside | antimetabolite; antineoplastic agent; antiviral drug; DNA synthesis inhibitor; EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor; environmental contaminant; immunosuppressive agent; photosensitizing agent; prodrug; radiosensitizing agent; xenobiotic |
| irinotecan [no description available] | 5.32 | 4 | 1 | carbamate ester; delta-lactone; N-acylpiperidine; pyranoindolizinoquinoline; ring assembly; tertiary alcohol; tertiary amino compound | antineoplastic agent; apoptosis inducer; EC 5.99.1.2 (DNA topoisomerase) inhibitor; prodrug |
| capecitabine Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers. | 9.41 | 1 | 1 | carbamate ester; cytidines; organofluorine compound | antimetabolite; antineoplastic agent; prodrug |
| docetaxel anhydrous Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group. | 4.45 | 1 | 1 | secondary alpha-hydroxy ketone; tetracyclic diterpenoid | antimalarial; antineoplastic agent; photosensitizing agent |
| epothilone a Epothilones: A group of 16-member MACROLIDES which stabilize MICROTUBULES in a manner similar to PACLITAXEL. They were originally found in the myxobacterium Sorangium cellulosum, now renamed to Polyangium (MYXOCOCCALES). | 4.45 | 1 | 1 | epothilone; epoxide | antineoplastic agent; metabolite; microtubule-stabilising agent; tubulin modulator |
| ixabepilone [no description available] | 4.45 | 1 | 1 | 1,3-thiazoles; beta-hydroxy ketone; epoxide; lactam; macrocycle | antineoplastic agent; microtubule-destabilising agent |
| taxane taxane: produced by Taxomyces andreanae | 9.41 | 1 | 1 | diterpene; terpenoid fundamental parent | |
| er-086526 eribulin: a halichondrin B derivative that suppresses microtubule growth and acts as an antimitotic agent; structure in first source. eribulin : A fully synthetic macrocyclic ketone analogue of marine sponge natural products. Inhibits growth phase of microtubules via tubulin-based antimitotic mechanism, which leads to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage | 4.45 | 1 | 1 | cyclic ketal; cyclic ketone; macrocycle; polycyclic ether; polyether; primary amino compound | antineoplastic agent; microtubule-destabilising agent |
| Condition | Indicated | Relationship Strength | Studies | Trials |
|---|---|---|---|---|
| Benign Neoplasms, Brain [description not available] | 0 | 7.75 | 6 | 4 |
| Breast Cancer [description not available] | 0 | 9.69 | 10 | 5 |
| Brain Neoplasms Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. | 0 | 7.75 | 6 | 4 |
| Breast Neoplasms Tumors or cancer of the human BREAST. | 0 | 9.69 | 10 | 5 |
| Cancer-Associated Pain [description not available] | 0 | 4.45 | 1 | 1 |
| Bone Cancer [description not available] | 0 | 4.45 | 1 | 1 |
| Breathlessness [description not available] | 0 | 4.45 | 1 | 1 |
| Lassitude [description not available] | 0 | 4.45 | 1 | 1 |
| Chronic Insomnia [description not available] | 0 | 4.45 | 1 | 1 |
| Cancer of Liver [description not available] | 0 | 4.45 | 1 | 1 |
| Cancer of Lung [description not available] | 0 | 5.43 | 2 | 2 |
| Emesis [description not available] | 0 | 4.45 | 1 | 1 |
| Cancer Pain Pain that may be caused by or related to cellular, tissue, and systemic changes that occur during NEOPLASM growth, tissue invasion, and METASTASIS. | 0 | 4.45 | 1 | 1 |
| Anorexia The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA. | 0 | 4.45 | 1 | 1 |
| Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. | 0 | 4.45 | 1 | 1 |
| Dyspnea Difficult or labored breathing. | 0 | 4.45 | 1 | 1 |
| Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. | 0 | 4.45 | 1 | 1 |
| Sleep Initiation and Maintenance Disorders Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition. | 0 | 4.45 | 1 | 1 |
| Liver Neoplasms Tumors or cancer of the LIVER. | 0 | 4.45 | 1 | 1 |
| Lung Neoplasms Tumors or cancer of the LUNG. | 0 | 5.43 | 2 | 2 |
| Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. | 0 | 4.45 | 1 | 1 |
| Vomiting The forcible expulsion of the contents of the STOMACH through the MOUTH. | 0 | 4.45 | 1 | 1 |
| Epithelial Ovarian Cancer [description not available] | 0 | 12.95 | 5 | 5 |
| Epithelial Neoplasms [description not available] | 0 | 7.95 | 5 | 5 |
| Cancer of Ovary [description not available] | 0 | 7.95 | 5 | 5 |
| Local Neoplasm Recurrence [description not available] | 0 | 9 | 8 | 8 |
| Carcinoma, Ovarian Epithelial A malignant neoplasm that originates in cells on the surface EPITHELIUM of the ovary and is the most common form of ovarian cancer. There are five histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Mutations in BRCA1, OPCML, PRKN, PIK3CA, AKT1, CTNNB1, RRAS2, and CDH1 genes are associated with this cancer. | 0 | 7.95 | 5 | 5 |
| Ovarian Neoplasms Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS. | 0 | 7.95 | 5 | 5 |
| Adverse Drug Event [description not available] | 0 | 3.56 | 1 | 1 |
| Carcinoma, Non-Small Cell Lung [description not available] | 0 | 3.56 | 1 | 1 |
| Cholera Infantum [description not available] | 0 | 3.56 | 1 | 1 |
| Metastase [description not available] | 0 | 10.7 | 3 | 2 |
| Carcinoma, Non-Small-Cell Lung A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy. | 0 | 3.56 | 1 | 1 |
| Neoplasm Metastasis The transfer of a neoplasm from one organ or part of the body to another remote from the primary site. | 0 | 5.7 | 3 | 2 |
| Drug-Related Side Effects and Adverse Reactions Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals. | 0 | 3.56 | 1 | 1 |
| Benign Neoplasms [description not available] | 0 | 5.11 | 3 | 1 |
| Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. | 0 | 5.11 | 3 | 1 |
| Experimental Neoplasms [description not available] | 0 | 2.1 | 1 | 0 |
| Glial Cell Tumors [description not available] | 0 | 3.5 | 1 | 1 |
| Glioma Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21) | 0 | 8.5 | 1 | 1 |