Page last updated: 2024-10-16

carbamates and Melanoma

carbamates has been researched along with Melanoma in 74 studies

Melanoma: A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)

Research Excerpts

ExcerptRelevanceReference
"In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment."9.41Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). ( Arance, A; Ascierto, PA; Dummer, R; Dutriaux, C; Flaherty, KT; Garbe, C; Gogas, H; Gollerkeri, A; Gutzmer, R; Jan de Willem, G; Krajsová, I; Liszkay, G; Loquai, C; Mandalà, M; Murris, J; Queirolo, P; Robert, C; Schadendorf, D; Sellier, AT; Sileni, VC; Suissa, J; Yamazaki, N, 2021)
"In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300)."9.34Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D, 2020)
"the favorable survival results and the attractive toxicity profile suggest that encorafenib and binimetinib combination is an intriguing standard option when targeted therapies are considered as first line treatment in BRAF mutated melanoma patients."9.05Safety and efficacy evaluation of encorafenib plus binimetinib for the treatment of advanced BRAF-mutant melanoma patients. ( Indini, A; Mandalà, M, 2020)
"The author summarizes the available data on binimetinib, a reversible inhibitor of the kinase activity of MEK1 and MEK2, in BRAF- and NRAS-mutated melanoma."9.05An overview of binimetinib for the treatment of melanoma. ( Specenier, P, 2020)
"Encorafenib has shown improved efficacy in the treatment of metastatic melanoma in comparison with vemurafenib."8.98Development of encorafenib for BRAF-mutated advanced melanoma. ( Dummer, R; Koelblinger, P; Thuerigen, O, 2018)
"Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions."8.12Development of Sesamol Carbamate-L-Phenylalanine Prodrug Targeting L-Type Amino Acid Transporter1 (LAT1) as a Potential Antiproliferative Agent against Melanoma. ( Bahrami, K; Järvinen, J; Rautio, J; Srisongkram, T; Timonen, J; Weerapreeyakul, N, 2022)
"The efficacy of encorafenib plus binimetinib (E + B) combination therapy for BRAF-mutated advanced melanoma as second-line therapy and beyond is still unknown."8.02Case series of BRAF-mutated advanced melanoma treated with encorafenib plus binimetinib combination therapy. ( Aiba, S; Amagai, R; Fujimura, T; Fujisawa, Y; Furudate, S; Hashimoto, A; Ito, T; Kambayashi, Y; Kato, H; Kunimoto, K; Maekawa, T; Matsushita, S; Muto, Y; Nakamura, Y; Ohuchi, K; Yamamoto, Y; Yoshino, K, 2021)
"The authors provide an overview of the preclinical development and the clinical trials that led to the use of encorafenib in BRAFV600-mutant melanoma."7.96Preclinical discovery and clinical development of encorafenib for the treatment of melanoma. ( Eroglu, Z; Ismail, S; Okten, IN; Withycombe, BM, 2020)
"A multicenter, retrospective case series investigation of consecutive BRAF-mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response."7.96Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. ( Amaria, RN; Amin, A; Davies, MA; Davis, JM; Diab, A; Glitza, IC; Holbrook, K; Lutzky, J; Patel, SP; Tawbi, H, 2020)
" Pyrexia or a spike of fever are well-known AE of BRAF inhibitors, with or without MEK inhibitors, and have been reported to have a high incidence after dabrafenib/trametinib, but not after encorafenib/binimetinib."7.96Severe pyrexia from nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. ( Aiba, S; Amagai, R; Fujimura, T; Hashimoto, A; Kambayashi, Y; Ohuchi, K; Sato, Y; Tanita, K, 2020)
"B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients."7.91The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. ( Barysch, M; Cheng, PF; Conrad, S; Dummer, R; Galliker, N; Goldinger, SM; Graf, NP; Koelblinger, P; Mangana, J, 2019)
" Encorafenib is a new BRAF inhibitor currently being tested in phase 3 clinical trials for advanced or metastatic melanoma as monotherapy or in combination with the MEK-inhibitor binimetinib."7.88Incomplete Vogt-Koyanagi-Harada disease following treatment with encorafenib and binimetinib for metastatic melanoma. ( Anastasopoulou, A; Diamantopoulos, PT; Gogas, H; Papaxoinis, G; Stoungioti, S, 2018)
"Malignant melanoma is a malignant tumor with a poor prognosis."5.72[Efficacy of the encorafenib + binimetinib combination in a BRAF mutated metastatic melanoma case report]. ( Di Guardo, L, 2022)
"Metastatic melanoma is often accompanied by the development of brain metastases, at presentation or during the course of therapy."5.62Complete response of brainstem metastasis in BRAF-mutated melanoma without stereotactic radiosurgery after initiation of encorafenib and binimetinib. ( Hanft, S; Khullar, K; Mehnert, JM; Weiner, JP, 2021)
"Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials."5.43Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells. ( Bi, X; Cheng, W; Gong, P; Jiang, K; Li, Z; Lin, G; Liu, J; Meng, S; Piao, Y; Song, F; Song, Z; Zhao, Y; Zhu, X, 2016)
"In COLUMBUS, treatment with encorafenib plus binimetinib in patients with advanced BRAF-mutant melanoma showed improved progression-free and overall survival with favourable tolerability compared to vemurafenib treatment."5.41Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS). ( Arance, A; Ascierto, PA; Dummer, R; Dutriaux, C; Flaherty, KT; Garbe, C; Gogas, H; Gollerkeri, A; Gutzmer, R; Jan de Willem, G; Krajsová, I; Liszkay, G; Loquai, C; Mandalà, M; Murris, J; Queirolo, P; Robert, C; Schadendorf, D; Sellier, AT; Sileni, VC; Suissa, J; Yamazaki, N, 2021)
"In part 1 of the COLUMBUS trial, 577 patients with advanced/metastatic BRAF V600-mutant melanoma, untreated or progressed after first-line immunotherapy, were randomised 1:1:1 to 450 mg of encorafenib QD + 45 mg of binimetinib BID (COMBO450) vs 960 mg of vemurafenib BID (VEM) or 300 mg of encorafenib ENCO QD (ENCO300)."5.34Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D, 2020)
"Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily."5.30Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management. ( Arance, A; Ascierto, PA; de Groot, JWB; Dummer, R; Dutriaux, C; Flaherty, KT; Garbe, C; Gogas, HJ; Gollerkeri, A; Gutzmer, R; Krajsova, I; Liszkay, G; Loquai, C; Mandala, M; Pickard, MD; Robert, C; Schadendorf, D; Sileni, VC; Yamazaki, N, 2019)
"The author summarizes the available data on binimetinib, a reversible inhibitor of the kinase activity of MEK1 and MEK2, in BRAF- and NRAS-mutated melanoma."5.05An overview of binimetinib for the treatment of melanoma. ( Specenier, P, 2020)
"the favorable survival results and the attractive toxicity profile suggest that encorafenib and binimetinib combination is an intriguing standard option when targeted therapies are considered as first line treatment in BRAF mutated melanoma patients."5.05Safety and efficacy evaluation of encorafenib plus binimetinib for the treatment of advanced BRAF-mutant melanoma patients. ( Indini, A; Mandalà, M, 2020)
"Encorafenib has shown improved efficacy in the treatment of metastatic melanoma in comparison with vemurafenib."4.98Development of encorafenib for BRAF-mutated advanced melanoma. ( Dummer, R; Koelblinger, P; Thuerigen, O, 2018)
"Sesamol is a compound reported to have anti-melanogenesis and anti-melanoma actions."4.12Development of Sesamol Carbamate-L-Phenylalanine Prodrug Targeting L-Type Amino Acid Transporter1 (LAT1) as a Potential Antiproliferative Agent against Melanoma. ( Bahrami, K; Järvinen, J; Rautio, J; Srisongkram, T; Timonen, J; Weerapreeyakul, N, 2022)
"The efficacy of encorafenib plus binimetinib (E + B) combination therapy for BRAF-mutated advanced melanoma as second-line therapy and beyond is still unknown."4.02Case series of BRAF-mutated advanced melanoma treated with encorafenib plus binimetinib combination therapy. ( Aiba, S; Amagai, R; Fujimura, T; Fujisawa, Y; Furudate, S; Hashimoto, A; Ito, T; Kambayashi, Y; Kato, H; Kunimoto, K; Maekawa, T; Matsushita, S; Muto, Y; Nakamura, Y; Ohuchi, K; Yamamoto, Y; Yoshino, K, 2021)
"Encorafenib (Braftovi) is indicated for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation, in combination with binimetinib (Mektovi)."4.02Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report. ( Lankheet, NAG; Meussen, E; Mian, P; Piersma, D, 2021)
"The authors provide an overview of the preclinical development and the clinical trials that led to the use of encorafenib in BRAFV600-mutant melanoma."3.96Preclinical discovery and clinical development of encorafenib for the treatment of melanoma. ( Eroglu, Z; Ismail, S; Okten, IN; Withycombe, BM, 2020)
" Pyrexia or a spike of fever are well-known AE of BRAF inhibitors, with or without MEK inhibitors, and have been reported to have a high incidence after dabrafenib/trametinib, but not after encorafenib/binimetinib."3.96Severe pyrexia from nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib. ( Aiba, S; Amagai, R; Fujimura, T; Hashimoto, A; Kambayashi, Y; Ohuchi, K; Sato, Y; Tanita, K, 2020)
"A multicenter, retrospective case series investigation of consecutive BRAF-mutant patients with melanoma brain metastases (MBMs) treated with a combination of BRAF inhibitor encorafenib and MEK inhibitor binimetinib was conducted to evaluate the antitumor response."3.96Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series. ( Amaria, RN; Amin, A; Davies, MA; Davis, JM; Diab, A; Glitza, IC; Holbrook, K; Lutzky, J; Patel, SP; Tawbi, H, 2020)
"B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients."3.91The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma. ( Barysch, M; Cheng, PF; Conrad, S; Dummer, R; Galliker, N; Goldinger, SM; Graf, NP; Koelblinger, P; Mangana, J, 2019)
" Encorafenib is a new BRAF inhibitor currently being tested in phase 3 clinical trials for advanced or metastatic melanoma as monotherapy or in combination with the MEK-inhibitor binimetinib."3.88Incomplete Vogt-Koyanagi-Harada disease following treatment with encorafenib and binimetinib for metastatic melanoma. ( Anastasopoulou, A; Diamantopoulos, PT; Gogas, H; Papaxoinis, G; Stoungioti, S, 2018)
"Human BRAF V600E-positive melanoma xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1."3.88Integrin-targeted quantitative optoacoustic imaging with MRI correlation for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma. ( Burton, NC; Cyran, CC; Eschbach, RS; Heimer, M; Hirner-Eppeneder, H; Kazmierczak, PM; Keinrath, G; Reiser, MF; Ricke, J; Schneider, MJ; Solyanik, O; Todica, A, 2018)
"Two male patients with stage IV metastatic BRAF-mutated melanoma were treated with a combination of a selective BRAF inhibitor and a selective MEK inhibitor (dabrafenib and trametinib, or encorafenib (LGX818) and binimetinib (MEK162)) within two different clinical trials."3.81Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor. ( Dummer, R; Galliker, NA; Goldinger, SM; Kamarashev, J; Murer, C, 2015)
"Encorafenib + binimetinib has a favourable efficacy profile compared to other double combination therapies and a favourable safety profile compared to both double and triple combination therapies."2.82Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis. ( Berardi, R; Corrie, P; Guidoboni, M; Kolovos, S; Laramée, P; Macabeo, B; Meyer, N; Schlueter, M; Trouiller, JB, 2022)
"Physicians who treat melanoma patients thus face news issues relating to prevention, detection and treatment of these adverse events."2.72[Management of toxicities of BRAF inhibitors and MEK inhibitors in advanced melanoma]. ( Baric, L; Cantagrel, A; Di Palma, M; Ederhy, S; Paques, M; Perlemuter, G; Sibaud, V, 2021)
"Malignant melanoma is increasing in frequency at a rapid rate in the United States."2.70Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study. ( Didolkar, MS; Eckardt, JR; Flaherty, LE; Samlowski, W; Sondak, VK; Taylor, SA; Unger, JM; Whitehead, RP, 2001)
"Malignant melanoma is a malignant tumor with a poor prognosis."1.72[Efficacy of the encorafenib + binimetinib combination in a BRAF mutated metastatic melanoma case report]. ( Di Guardo, L, 2022)
"Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood."1.62Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries. ( Al-Kindi, S; Barnholtz-Sloan, JS; de Lima, M; Dowlati, A; Fradley, MG; Guha, A; Gutierrez, JM; Jain, C; Jain, P; Lenihan, D; Oliveira, GH, 2021)
"Metastatic melanoma is often accompanied by the development of brain metastases, at presentation or during the course of therapy."1.62Complete response of brainstem metastasis in BRAF-mutated melanoma without stereotactic radiosurgery after initiation of encorafenib and binimetinib. ( Hanft, S; Khullar, K; Mehnert, JM; Weiner, JP, 2021)
"Encorafenib (LGX818) is a new-generation BRAF inhibitor that is under evaluation in clinical trials."1.43Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells. ( Bi, X; Cheng, W; Gong, P; Jiang, K; Li, Z; Lin, G; Liu, J; Meng, S; Piao, Y; Song, F; Song, Z; Zhao, Y; Zhu, X, 2016)

Research

Studies (74)

TimeframeStudies, this research(%)All Research%
pre-199010 (13.51)18.7374
1990's0 (0.00)18.2507
2000's3 (4.05)29.6817
2010's32 (43.24)24.3611
2020's29 (39.19)2.80

Authors

AuthorsStudies
Sato, T1
Noto, M1
Yamada, M1
Kono, M1
Schadendorf, D7
Dummer, R11
Robert, C7
Ribas, A1
Sullivan, RJ2
Panella, T1
McKean, M1
Santos, ES1
Brill, K1
Polli, A1
Pietro, AD1
Ascierto, PA8
Miura, S1
Onishi, M1
Watabe, D1
Amano, H1
Di Guardo, L1
Srisongkram, T1
Bahrami, K1
Järvinen, J1
Timonen, J1
Rautio, J1
Weerapreeyakul, N1
Corrie, P1
Meyer, N2
Berardi, R1
Guidoboni, M1
Schlueter, M1
Kolovos, S1
Macabeo, B1
Trouiller, JB1
Laramée, P1
Gogas, HJ4
Flaherty, KT5
Arance, A5
Mandala, M6
Liszkay, G5
Garbe, C6
Krajsova, I5
Gutzmer, R6
Sileni, VC2
Dutriaux, C4
de Groot, JWB4
Yamazaki, N4
Loquai, C5
Gollerkeri, A3
Pickard, MD5
Kattan, J1
Kattan, C1
Farhat, F1
Assi, T1
Ngo, P1
Bycroft, R1
Holbrook, K1
Lutzky, J1
Davies, MA1
Davis, JM1
Glitza, IC1
Amaria, RN1
Diab, A1
Patel, SP1
Amin, A1
Tawbi, H1
Carr, MJ1
Sun, J1
Eroglu, Z2
Zager, JS1
Limmer, A1
Swali, R1
Robare, S1
Specenier, P1
Amagai, R2
Fujimura, T2
Kambayashi, Y2
Sato, Y1
Tanita, K1
Ohuchi, K2
Hashimoto, A2
Aiba, S2
Matsudate, Y1
Weber, J1
Patel, S1
Carlino, MS1
Tan, DSW1
Lebbé, C1
Siena, S1
Elez, E1
Wollenberg, L1
Sandor, V3
Okten, IN1
Ismail, S1
Withycombe, BM1
Lang, N1
Schinaia, CG1
Wolfsperger, F1
Schaller, M1
Forchhammer, S1
Forschner, A1
Indini, A1
Anbar, HS1
El-Gamal, MI1
Tarazi, H1
Lee, BS1
Jeon, HR1
Kwon, D1
Oh, CH1
Byron, Y1
Nott, L1
Shackleton, M1
Warburton, L1
Meniawy, TM1
Calapre, L1
Pereira, M1
McEvoy, A1
Ziman, M1
Gray, ES1
Millward, M1
Yoshino, K1
Kato, H1
Fujisawa, Y1
Nakamura, Y1
Yamamoto, Y1
Kunimoto, K1
Ito, T1
Matsushita, S1
Maekawa, T1
Muto, Y1
Furudate, S1
Mian, P1
Meussen, E1
Piersma, D1
Lankheet, NAG1
Sibaud, V1
Baric, L1
Cantagrel, A1
Di Palma, M1
Ederhy, S1
Paques, M1
Perlemuter, G1
Spagnolo, F1
Ramtohul, P1
Denis, D1
Comet, A1
Guha, A1
Jain, P1
Fradley, MG1
Lenihan, D1
Gutierrez, JM1
Jain, C1
de Lima, M1
Barnholtz-Sloan, JS1
Oliveira, GH1
Dowlati, A1
Al-Kindi, S1
Khullar, K1
Hanft, S1
Mehnert, JM1
Weiner, JP1
Gogas, H2
Queirolo, P1
Jan de Willem, G1
Sellier, AT1
Suissa, J1
Murris, J1
Cullen, GD1
Finnes, HD1
Markovic, SN1
Volcheck, GW1
Daud, A1
Tsai, K1
Maanaoui, M1
Saint-Jacques, C1
Gnemmi, V1
Frimat, M1
Lionet, A1
Hazzan, M1
Noël, C1
Provot, F1
Flaherty, K1
Russo, I1
Zorzetto, L1
Frigo, AC1
Chiarion Sileni, V2
Alaibac, M1
Schaper-Gerhardt, K1
Okoye, S1
Herbst, R1
Ulrich, J1
Terheyden, P1
Pföhler, C1
Utikal, JS1
Kreuter, A1
Mohr, P1
Dippel, E1
Satzger, I1
Sucker, A1
Ugurel, S1
Koelblinger, P2
Thuerigen, O1
Fernández-Sartorio, C1
Boada, A1
Chavez-Bourgeois, MM1
Ruiz Ares, GJ1
Arance, AM1
Manzano, JL1
García-Herrera, A1
Carrera, C1
Grob, JJ1
Chiarion-Sileni, V1
Moutouh-de Parseval, LA2
Sidaway, P1
Shirley, M1
Diamantopoulos, PT1
Stoungioti, S1
Anastasopoulou, A1
Papaxoinis, G1
Martin-Liberal, J1
Kazmierczak, PM1
Burton, NC1
Keinrath, G1
Hirner-Eppeneder, H1
Schneider, MJ1
Eschbach, RS1
Heimer, M1
Solyanik, O1
Todica, A1
Reiser, MF1
Ricke, J1
Cyran, CC1
Graf, NP1
Galliker, N1
Conrad, S1
Barysch, M1
Mangana, J2
Cheng, PF2
Goldinger, SM2
Trojaniello, C1
Festino, L1
Vanella, V1
Brue, A1
Benzaquen, M1
Bonnet, N1
Koeppel, MC1
Default, A1
Delaporte, E1
Berbis, P1
Livingstone, E1
Rose, AAN1
Paulitschke, V1
Eichhoff, O1
Gerner, C1
Paulitschke, P1
Bileck, A1
Mohr, T1
Leitner, A1
Guenova, E1
Saulite, I1
Freiberger, SN1
Irmisch, A1
Knapp, B1
Zila, N1
Chatziisaak, TP1
Stephan, J1
Kunstfeld, R1
Pehamberger, H1
Aebersold, R1
Levesque, MP1
Anforth, RM1
Carlos, GR1
Scolyer, RA1
Chou, S1
Fernandez-Peñas, P1
Deuker, MM1
Marsh Durban, V1
Phillips, WA1
McMahon, M1
Cheng, H1
Aplin, AE1
Galliker, NA1
Murer, C1
Kamarashev, J1
Li, Z1
Jiang, K1
Zhu, X1
Lin, G1
Song, F1
Zhao, Y1
Piao, Y1
Liu, J1
Cheng, W1
Bi, X1
Gong, P1
Song, Z1
Meng, S1
Vanhaecke, C1
Deilhes, F1
Chanal, J1
Regnier-Rosencher, E1
Boitier, F1
Boulinguez, S1
Avril, MF1
Guégan, S1
Dupin, N1
Aractingi, S1
Kramkimel, N1
Turner, MC1
Rossfeld, K1
Salama, AK1
Tyler, D1
Beasley, G1
Ryan, CW1
Shulman, KL1
Richards, JM1
Kugler, JW1
Sosman, JA1
Ansari, RH1
Vokes, EE1
Vogelzang, NJ1
Jordan, AM1
Khan, TH1
Malkin, H1
Osborn, HM1
Photiou, A1
Riley, PA1
Whitehead, RP1
Unger, JM1
Flaherty, LE1
Eckardt, JR1
Taylor, SA1
Didolkar, MS1
Samlowski, W1
Sondak, VK1
De Clerck, F1
De Brabander, M1
De Brabander, MJ1
Van de Veire, RM1
Aerts, FE1
Borgers, M1
Janssen, PA1
Mufson, RA1
Atassi, G1
Tagnon, HJ1
Hortobagyi, GN2
Hersh, EM1
Papadopoulos, NE1
Frye, D1
Rios, A1
Reuben, JM1
Plager, C1
Rosenblum, M1
Quesada, J1
Rosenblum, MG1
Okun, MR1
Donnellan, B1
Patel, RP1
Edelstein, LM1
Luce, JK1
Bodey, GP1
Prabhakaran, K1
Harris, EB1
Kirchheimer, WF1
Pomerantz, SH1

Clinical Trials (4)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A PHASE 3, RANDOMIZED, DOUBLE-BLIND STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS PLACEBO PLUS PEMBROLIZUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE METASTATIC OR UNRESECTABLE LOCALLY ADVANCED MELANOMA[NCT04657991]Phase 3624 participants (Anticipated)Interventional2021-01-15Recruiting
A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma[NCT01909453]Phase 3921 participants (Actual)Interventional2013-12-13Active, not recruiting
A Phase 1B Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of the Combination of Encorafenib, Binimetinib and Palbociclib in Patients With BRAF-mutant Metastatic Melanoma (The CELEBRATE Study)[NCT04720768]Phase 1/Phase 278 participants (Anticipated)Interventional2020-06-04Recruiting
A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors[NCT01543698]Phase 1/Phase 2189 participants (Actual)Interventional2012-05-28Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Part 1 and Part 2: Disease Control Rate (DCR)

DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionpercentage of participants (Number)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)92.2
Part 1: LGX818 300 mg84.0
Part 1: Vemurafenib 960 mg BID81.7
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)90.7
Part 2: LGX818 300 mg79.1
Part 1 + Part 2: LGX818 300 mg82.5

Part 1 and Part 2: Duration of Response (DOR)

DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)16.6
Part 1: LGX818 300 mg15.2
Part 1: Vemurafenib 960 mg BID12.3
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)12.7
Part 2: LGX818 300 mg7.5
Part 1 + Part 2: LGX818 300 mg12.9

Part 1 and Part 2: Objective Response Rate (ORR)

ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionpercentage of participants (Number)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)63.0
Part 1: LGX818 300 mg50.5
Part 1: Vemurafenib 960 mg BID40.3
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)65.9
Part 2: LGX818 300 mg50.0
Part 1 + Part 2: LGX818 300 mg50.4

Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50 percent (%) of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)NA
Part 1: LGX818 300 mg26.7
Part 1: Vemurafenib 960 mg BID18.2
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)NA
Part 2: LGX818 300 mg10.2
Part 1 + Part 2: LGX818 300 mg19.2

Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale

FACT-M:melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items,not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause. (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)NA
Part 1: LGX818 300 mg30.5
Part 1: Vemurafenib 960 mg BID22.1
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)NA
Part 2: LGX818 300 mgNA
Part 1 + Part 2: LGX818 300 mg20.5

Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)

"EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical, role, cognitive, emotional, social functioning), 3 multi-item symptom scales (fatigue, nausea/vomiting, and pain), global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea, sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from not at all to very much and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score represented better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause." (NCT01909453)
Timeframe: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)23.9
Part 1: LGX818 300 mg14.7
Part 1: Vemurafenib 960 mg BID16.6
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18.4
Part 2: LGX818 300 mg9.5
Part 1 + Part 2: LGX818 300 mg11.1

Part 1 and Part 2: Time to Objective Response (TTR)

TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit [FPFV] to last patient last visit [LPLV] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review. (NCT01909453)
Timeframe: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)1.9
Part 1: LGX818 300 mg2.0
Part 1: Vemurafenib 960 mg BID2.1
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1.9
Part 2: LGX818 300 mg1.9
Part 1 + Part 2: LGX818 300 mg1.9

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)14.9
Part 1: LGX818 300 mg9.6

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm^2). (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)

Interventionmonths (Median)
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)14.9
Part 1: Vemurafenib 960 mg BID7.3

Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group

PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm^2. (NCT01909453)
Timeframe: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)

Interventionmonths (Median)
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)12.9
Part 2: LGX818 300 mg7.4
Part 1 + Part 2: LGX818 300 mg9.2

Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg74.201.792.96-3.62-0.60-2.69-6.41-2.121.792.7816.675.56
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)73.047.296.159.379.2210.568.6610.5910.338.3313.13-4.17

Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg74.380.321.98-0.911.26-0.740.831.303.261.27-0.762.94-0.32-0.83
Part 1: LGX818 300 mg74.46-0.341.540.342.150.123.782.303.641.00-1.162.94-0.32-3.57
Part 1: Vemurafenib 960 mg BID72.311.882.032.71-0.174.53-2.25-5.46-1.390.38-3.13-0.69-1.1912.50
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)74.683.235.375.424.474.813.527.355.334.254.17-1.743.9241.67

Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg0.73-0.06-0.06-0.16-0.11-0.16-0.20-0.26-0.20-0.11-0.11-0.06
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)0.750.060.070.060.070.060.050.050.060.050.12-0.27

Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg0.75-0.09-0.13-0.14-0.14-0.17-0.18-0.20-0.15-0.17-0.14-0.11-0.11-0.08
Part 1: LGX818 300 mg0.76-0.10-0.15-0.13-0.15-0.18-0.17-0.18-0.14-0.18-0.14-0.11-0.11-0.09
Part 1: Vemurafenib 960 mg BID0.730.00-0.04-0.03-0.04-0.01-0.02-0.07-0.02-0.02-0.04-0.05-0.17-0.14
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)0.740.050.040.050.030.040.050.050.070.030.070.040.070.03

Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg67.39-4.95-4.72-7.08-8.73-7.53-9.29-12.75-7.14-0.930.004.17
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)65.954.475.615.014.944.765.896.115.861.233.03-6.25

Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg66.48-6.81-7.87-8.53-10.96-10.13-8.80-10.56-7.85-8.05-10.80-5.64-7.054.63
Part 1: LGX818 300 mg66.07-7.64-9.24-9.21-12.03-11.27-8.59-9.91-8.03-9.33-11.05-5.64-7.054.76
Part 1: Vemurafenib 960 mg BID64.74-3.46-4.05-3.04-6.94-3.80-2.93-10.34-6.94-1.89-8.85-3.47-2.38-4.17
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)66.723.561.551.53-0.550.810.425.020.41-0.510.74-1.391.960.00

Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg81.45-13.63-12.63-17.01-15.83-13.49-13.85-24.31-19.05-14.07-13.33-4.44
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)80.672.942.731.223.030.500.47-0.40-0.88-5.71-8.48-5.00

Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg82.63-13.74-15.74-16.49-18.27-19.87-18.22-21.18-18.91-19.14-16.78-14.46-15.93-2.00
Part 1: LGX818 300 mg83.18-13.79-17.14-16.26-19.43-22.65-20.00-20.26-18.88-20.07-16.86-14.46-15.93-0.95
Part 1: Vemurafenib 960 mg BID80.71-2.90-7.45-6.98-6.82-4.11-6.30-6.22-3.27-1.90-4.90-2.22-4.76-15.00
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)82.100.200.15-1.93-0.45-0.85-1.250.29-0.03-1.22-0.95-5.00-5.4933.33

Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg78.31-10.00-5.11-13.89-9.52-12.37-5.77-15.69-7.14-12.96-33.330.00
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)81.374.053.373.053.661.951.752.861.591.234.55-16.67

Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

"EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from not at all to very much and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms." (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1 + Part 2: LGX818 300 mg80.09-10.59-9.80-11.11-13.70-12.54-9.74-11.78-10.54-12.43-15.15-6.37-7.05-13.33
Part 1: LGX818 300 mg80.91-10.86-11.92-9.80-15.71-12.62-11.38-10.63-11.42-12.33-14.73-6.37-7.05-19.05
Part 1: Vemurafenib 960 mg BID78.54-4.90-7.21-2.75-1.99-0.36-0.45-6.321.393.79-3.131.394.76-8.33
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)80.69-0.663.262.821.57-2.72-4.273.731.11-1.04-1.52-12.32-5.2125.00

Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at End of treatment visit
Part 2: LGX818 300 mg51.13-2.16-0.60-3.14-1.83-2.41-3.31-4.14-2.640.00-2.00-1.61
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)52.082.792.582.643.232.541.972.082.451.232.586.58

Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit

FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each),emotional well-being (6 items),surgery specific concerns related to melanoma(8 items, not included in this study). Each item range from 0(not at all) to 4(very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172,higher scores represented better quality of life. Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. (NCT01909453)
Timeframe: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)

,,,
Interventionunits on a scale (Mean)
BaselineChange at Cycle 3 Day 1Change at Cycle 5 Day 1Change at Cycle 7 Day 1Change at Cycle 9 Day 1Change at Cycle 11 Day 1Change at Cycle 13 Day 1Change at Cycle 15 Day 1Change at Cycle 17 Day 1Change at Cycle 19 Day 1Change at Cycle 21 Day 1Change at Cycle 23 Day 1Change at Cycle 25 Day 1Change at End of treatment visit
Part 1: Vemurafenib 960 mg BID52.01-1.55-1.90-2.19-1.90-0.51-0.97-1.720.700.23-3.33-0.17-0.14-2.31
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)52.390.92-0.011.350.520.18-0.330.400.27-0.59-0.69-1.67-1.8318.50
Part 1 + Part 2: LGX818 300 mg52.24-3.14-2.78-3.08-2.39-3.29-2.88-2.88-1.88-2.38-2.58-1.38-1.00-3.81
Part 1: LGX818 300 mg52.76-3.58-3.77-3.05-2.69-3.67-2.71-2.48-1.66-2.80-2.59-1.38-1.00-5.18

Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. (NCT01909453)
Timeframe: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)

,,,,,
InterventionParticipants (Count of Participants)
Baseline: ECOG score 0Baseline: ECOG score 1Cycle 2 Day 1: ECOG score 0Cycle 2 Day 1: ECOG score 1Cycle 2 Day 1: ECOG score 2Cycle 2 Day 1: ECOG score 3Cycle 2 Day 1: ECOG score 4Cycle 3 Day 1: ECOG score 0Cycle 3 Day 1: ECOG score 1Cycle 3 Day 1: ECOG score 2Cycle 4 Day 1: ECOG score 0Cycle 4 Day 1: ECOG score 1Cycle 4 Day 1: ECOG score 2Cycle 4 Day 1: ECOG score 3Cycle 5 Day 1: ECOG score 0Cycle 5 Day 1: ECOG score 1Cycle 5 Day 1: ECOG score 2Cycle 5 Day 1: ECOG score 3Cycle 5 Day 1: ECOG score 4Cycle 6 Day 1: ECOG score 0Cycle 6 Day 1: ECOG score 1Cycle 6 Day 1: ECOG score 2Cycle 6 Day 1: ECOG score 3Cycle 6 Day 1: ECOG score 4Cycle 7 Day 1: ECOG score 0Cycle 7 Day 1: ECOG score 1Cycle 7 Day 1: ECOG score 2Cycle 8 Day 1: ECOG score 0Cycle 8 Day 1: ECOG score 1Cycle 8 Day 1: ECOG score 2Cycle 8 Day 1: ECOG score 3Cycle 9 Day 1: ECOG score 0Cycle 9 Day 1: ECOG score 1Cycle 9 Day 1: ECOG score 2Cycle 9 Day 1: ECOG score 3Cycle 9 Day 1: ECOG score 4Cycle 9 Day 1: ECOG score 5Cycle 10 Day 1: ECOG score 0Cycle 10 Day 1: ECOG score 1Cycle 10 Day 1: ECOG score 2Cycle 10 Day 1: ECOG score 3Cycle 11 Day 1: ECOG score 0Cycle 11 Day 1: ECOG score 1Cycle 11 Day 1: ECOG score 2Cycle 11 Day 1: ECOG score 3Cycle 12 Day 1: ECOG score 0Cycle 12 Day 1: ECOG score 1Cycle 12 Day 1: ECOG score 2Cycle 12 Day 1: ECOG score 3Cycle 12 Day 1: ECOG score 4Cycle 13 Day 1: ECOG score 0Cycle 13 Day 1: ECOG score 1Cycle 13 Day 1: ECOG score 2Cycle 13 Day 1: ECOG score 4Cycle 14 Day 1: ECOG score 0Cycle 14 Day 1: ECOG score 1Cycle 14 Day 1: ECOG score 2Cycle 14 Day 1: ECOG score 3Cycle 14 Day 1: ECOG score 4Cycle 15 Day 1: ECOG score 0Cycle 15 Day 1: ECOG score 1Cycle 15 Day 1: ECOG score 2Cycle 15 Day 1: ECOG score 3Cycle 15 Day 1: ECOG score 4Cycle 16 Day 1: ECOG score 0Cycle 16 Day 1: ECOG score 1Cycle 16 Day 1: ECOG score 2Cycle 16 Day 1: ECOG score 3Cycle 17 Day 1: ECOG score 0Cycle 17 Day 1: ECOG score 1Cycle 17 Day 1: ECOG score 2Cycle 18 Day 1: ECOG score 0Cycle 18 Day 1: ECOG score 1Cycle 18 Day 1: ECOG score 2Cycle 18 Day 1: ECOG score 3Cycle 19 Day 1: ECOG score 0Cycle 19 Day 1: ECOG score 1Cycle 19 Day 1: ECOG score 2Cycle 20 Day 1: ECOG score 0Cycle 20 Day 1: ECOG score 1Cycle 20 Day 1: ECOG score 2Cycle 20 Day 1: ECOG score 3Cycle 21 Day 1: ECOG score 0Cycle 21 Day 1: ECOG score 1Cycle 21 Day 1: ECOG score 2Cycle 22 Day 1: ECOG score 0Cycle 22 Day 1: ECOG score 1Cycle 22 Day 1: ECOG score 3Cycle 22 Day 1: ECOG score 4Cycle 23 Day 1: ECOG score 0Cycle 23 Day 1: ECOG score 1Cycle 24 Day 1: ECOG score 0Cycle 24 Day 1: ECOG score 1Cycle 25 Day 1: ECOG score 0Cycle 25 Day 1: ECOG score 1Cycle 26 Day 1: ECOG score 0Cycle 26 Day 1: ECOG score 1Cycle 26 Day 1: ECOG score 2Cycle 27 Day 1: ECOG score 0Cycle 27 Day 1: ECOG score 1Cycle 28 Day 1: ECOG score 0Cycle 28 Day 1: ECOG score 1Cycle 29 Day 1: ECOG score 0Cycle 29 Day 1: ECOG score 1Cycle 30 Day 1: ECOG score 0Cycle 30 Day 1: ECOG score 1Cycle 31 Day 1: ECOG score 0Cycle 31 Day 1: ECOG score 1
Part 1 + Part 2: LGX818 300 mg1997714211172013011361289671118100600979061195872777061726711007053206156405549210554630623720154372005230404833241290040261342220312012716112612231023821802061861359373
Part 1: LGX818 300 mg139539879320908149366418569400686530168601554931504710005235104440104431110413110472700141301004123303927136240038201311920291912716112612231023821802061861359373
Part 1: Vemurafenib 960 mg BID13551113644001076449852448252711784611074352583340553041004326213920213216210271820251920022181002410102111118111120911980015801160010595927203441504020
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)136561424410113153112850101284231012445000111461112332110236401194323088302084251007722107423000722011064241065161601410549253701361092980024621717314315353120000
Part 2: LGX818 300 mg602444324004032235303033312002925310272712221302220010018181017163011181001415201510200137100117109615500260330021000000000000000000000000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18968193621001975511895641181552101685831115858214058111355200101214631116420011338001102391110033210822710164230152151341110227115500112042000000000000000000000

Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Hemoglobin (hypo)Prothrombin international normalized ratio increasedLymphocytes (hypo)Lymphocytes (hyper)Neutrophils (hypo)Platelets (hypo)Leukocytes (hypo)Albumin (hypo)Alkaline phosphataseAlanine aminotransferaseAspartate aminotransferaseBilirubinCreatine (phospho)kinaseCorrected Calcium (hypo)Corrected Calcium (hyper)CreatinineGamma-glutamyl transferaseGlucose serum fasting (hypo)Glucose serum fasting (hyper)Magnesium (hypo)Magnesium (hyper)Phosphate (hypo)Potassium (hypo)Potassium (hyper)Sodium (hypo)
Part 1: LGX818 300 mg11115115135384011015294121025141
Part 1: Vemurafenib 960 mg BID13341531424841313248153120135361
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)190201414253615121321035432200218167

Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
RashSkin infectionsPPE syndromePhotosensitivityNail disordersSevere cutaneous adverse reactions
Part 1: LGX818 300 mg10126001
Part 1: Vemurafenib 960 mg BID2502305
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)240100

Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values

Newly occurring notable ECG values were reported for QT (millisecond [ms]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (>) 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60. Heart rate: New <60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
QT: Increase >30 msQT: Increase >60 msQT: New >450 msQT: New >480 msQT: New >500 msQTcF: Increase >30 msQTcF: Increase >60 msQTcF: New >450 msQTcF: New >480 msQTcF: New >500 msQTcB: Increase >30 msQTcB: Increase >60 msQTcB: New >450 msQTcB: New >480 msQTcB: New >500 msHeart rate: New <60 bpmHeart rate: New <100 bpm
Part 1: LGX818 300 mg68191542567397574157623103723
Part 1: Vemurafenib 960 mg BID81241732761042537814652081618
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)105272352501025714711471235814

Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high diastolic blood pressure (DBP) [mmHg]: <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 beats per minute (bpm) with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight [kilogram]: >=20 percent (%) decrease from baseline/>= 10% increase from baseline. Low/high Body temperature degree Celsius (C): <= 36 degree C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Sitting Pulse Rate (bpm): HighSitting Pulse Rate (bpm): LowSitting Systolic Blood Pressure (mmHg): HighSitting Systolic Blood Pressure (mmHg): LowSitting Diastolic Blood Pressure (mmHg): HighSitting Diastolic Blood Pressure (mmHg): LowWeight (kg): HighWeight (kg): LowBody temperature (degree C): HighBody temperature (degree C): Low
Part 1: LGX818 300 mg78144571081174
Part 1: Vemurafenib 960 mg BID823111358131757
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)132772394421976

Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Retinopathy excluding RVORVOUveitis-type events
Part 1: LGX818 300 mg010
Part 1: Vemurafenib 960 mg BID000
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)501

Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
InterventionParticipants (Count of Participants)
Grade 0Grade 2Grade 3Grade 4Missing
Part 1: LGX818 300 mg161174010
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)12756306
Part 1: Vemurafenib 960 mg BID16116207

Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

,,
Interventionpercentage of participants (Number)
Participants with AEsParticipants with SAEs
Part 1: LGX818 300 mg99.534.9
Part 1: Vemurafenib 960 mg BID99.537.1
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)98.434.4

Part 1: Plasma Concentrations of LGX 818

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

,
Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1: LGX818 300 mg58.111904090185073.653.8
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)18.6164068603400119150

Part 1: Plasma Concentrations of MEK162

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450)2.9542683233081.068.1

Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Hemoglobin (hypo)Prothrombin international normalized ratio increasedLymphocytes (hypo)Lymphocytes (hyper)Neutrophils (hypo)Platelets (hypo)Leukocytes (hypo)Albumin (hypo)Alkaline phosphatase (hyper)Alanine aminotransferaseAspartate aminotransferaseBilirubinCreatine kinaseCorrected Calcium (hypo)CreatinineGamma-glutamyl transferaseGlucose serum fasting (hypo)Glucose serum fasting (hyper)Magnesium (hypo)Magnesium (hyper)Phosphate (hypo)Potassium (hypo)Potassium (hyper)Sodium (hypo)Sodium (hyper)
Part 1 + Part 2: LGX818 300 mg16125139259495012263841710331730
Part 2: LGX818 300 mg501024124111001119050080320
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1642811191371118152404443832703262842

Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
RashSkin infectionPPE syndromePhotosensitivityNail disordersSevere cutaneous adverse reactions
Part 1 + Part 2: LGX818 300 mg13130001
Part 2: LGX818 300 mg304000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)271000

Part 2: Number of Participants With Newly Occurring Notable ECG Values

Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New >450, New >480, New >500, increase from baseline >30, Increase from baseline >60. Heart rate: New < 60, New >100 was considered as newly occurring notable value. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
QT (ms): Increase from baseline > 30QT (ms): Increase from baseline > 60QT (ms): New > 450QT (ms): New > 480QT (ms): New > 500QTcF (ms): Increase from baseline > 30QTcF (ms): Increase from baseline > 60QTcF (ms): New > 450QTcF (ms): New > 480QTcF (ms): New > 500QTcB (ms): New > 450QTcB (ms): New > 480QTcB (ms): New > 500QTcB (ms): Increase from baseline > 30QTcB (ms): Increase from baseline > 60Heart rate (bpm): New < 60Heart rate (bpm): New > 100
Part 1 + Part 2: LGX818 300 mg95252062761450126104291198234233
Part 2: LGX818 300 mg27652020711512861248510
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1323434945913361127023106922828

Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg, Low/high diastolic blood pressure (DBP) [mmHg]: <=50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg, Low/high pulse rate [bpm]: <=50 bpm with decrease from baseline of >=15 bpm/>=120 bpm with increase from baseline of >=15 bpm, Low/high weight (kg): >=20 % decrease from baseline/>= 10% increase from baseline Low/high Body temperature degree C): <= 36°C/>= 37.5 degree C. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Sitting Pulse Rate (bpm): HighSitting Pulse Rate (bpm): LowSitting Systolic Blood Pressure (mmHg): HighSitting Systolic Blood Pressure (mmHg): LowSitting Diastolic Blood Pressure (mmHg): HighSitting Diastolic Blood Pressure (mmHg): LowWeight (kg): HighWeight (kg): LowBody temperature (°C): HighBody temperature (°C): Low
Part 1 + Part 2: LGX818 300 mg109178791191696
Part 2: LGX818 300 mg31342211522
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)711401041746014120

Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AEs of grade 3 or 4 are reported in this outcome measure. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Retinopathy excluding RVORVOUveitis-type events
Part 1 + Part 2: LGX818 300 mg010
Part 2: LGX818 300 mg000
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)404

Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline LVEF Values were graded as Grade 0: Non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%;Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
InterventionParticipants (Count of Participants)
Grade 0Grade 2Grade 3Grade 4Missing
Part 1 + Part 2: LGX818 300 mg235224015
Part 2: LGX818 300 mg745005
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)18171302

Part 2: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence; Grade 5: death. AEs of all grades were reported. (NCT01909453)
Timeframe: Baseline up to 30 days after last dose of study drug (up to 36 months)

,,
Interventionpercentage of Participants (Number)
AEsSAEs
Part 1 + Part 2: LGX818 300 mg98.633.3
Part 2: LGX818 300 mg96.429.8
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)98.129.2

Part 2: Plasma Concentrations of LGX 818

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

,,
Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 1 + Part 2: LGX818 300 mg39.712504170198060.160.6
Part 2: LGX818 300 mg0.014513704310225029.579.5
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)5.0213604390242012174.1

Part 2: Plasma Concentrations of MEK162

(NCT01909453)
Timeframe: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose

Interventionnanogram per milliliter (Mean)
Cycle 1 Day 1: pre-doseCycle 1 Day 1: 0.5 hours post doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 4 to 8 hours post doseCycle 2 Day 1: pre-doseCycle 3 Day 1: pre-dose
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300)1.6836664228772.373.2

Reviews

13 reviews available for carbamates and Melanoma

ArticleYear
STARBOARD: encorafenib + binimetinib + pembrolizumab for first-line metastatic/unresectable
    Future oncology (London, England), 2022, Volume: 18, Issue:17

    Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; C

2022
Comparative efficacy and safety of targeted therapies for BRAF-mutant unresectable or metastatic melanoma: Results from a systematic literature review and a network meta-analysis.
    Cancer treatment reviews, 2022, Volume: 110

    Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Benzimidazoles; Carbamates; Humans; M

2022
An evaluation of encorafenib for the treatment of melanoma.
    Expert opinion on pharmacotherapy, 2020, Volume: 21, Issue:2

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanoma; Mutati

2020
An overview of binimetinib for the treatment of melanoma.
    Expert opinion on pharmacotherapy, 2020, Volume: 21, Issue:7

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Clinical Trials as Topic

2020
Safety and efficacy evaluation of encorafenib plus binimetinib for the treatment of advanced BRAF-mutant melanoma patients.
    Expert opinion on drug safety, 2020, Volume: 19, Issue:10

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanom

2020
[Management of toxicities of BRAF inhibitors and MEK inhibitors in advanced melanoma].
    Bulletin du cancer, 2021, Volume: 108, Issue:5

    Topics: Antineoplastic Combined Chemotherapy Protocols; Azetidines; Benzimidazoles; Carbamates; Drug Combina

2021
Management of Treatment-Related Adverse Events with Agents Targeting the MAPK Pathway in Patients with Metastatic Melanoma.
    The oncologist, 2017, Volume: 22, Issue:7

    Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azetidines; Benzimidazoles; C

2017
Development of encorafenib for BRAF-mutated advanced melanoma.
    Current opinion in oncology, 2018, Volume: 30, Issue:2

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carbamates; Clinical Trials, Phase III as T

2018
Encorafenib and Binimetinib: First Global Approvals.
    Drugs, 2018, Volume: 78, Issue:12

    Topics: Benzimidazoles; Carbamates; Drug Approval; Humans; MAP Kinase Kinase Kinases; Melanoma; Molecular St

2018
[What's new in oncodermatology?]
    Annales de dermatologie et de venereologie, 2018, Volume: 145 Suppl 7

    Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Ben

2018
Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.
    Expert review of clinical pharmacology, 2019, Volume: 12, Issue:3

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Disease-Free Su

2019
Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma.
    Drugs of today (Barcelona, Spain : 1998), 2019, Volume: 55, Issue:4

    Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Pr

2019
Can binimetinib, encorafenib and masitinib be more efficacious than currently available mutation-based targeted therapies for melanoma treatment?
    Expert opinion on pharmacotherapy, 2017, Volume: 18, Issue:5

    Topics: Benzamides; Benzimidazoles; Carbamates; Humans; Melanoma; Mutation; Piperidines; Protein Kinase Inhi

2017

Trials

9 trials available for carbamates and Melanoma

ArticleYear
Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
    European journal of cancer (Oxford, England : 1990), 2019, Volume: 119

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Fatigue; Female; Humans;

2019
Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma.
    European journal of cancer (Oxford, England : 1990), 2020, Volume: 126

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carb

2020
A Phase Ib/II Study of the BRAF Inhibitor Encorafenib Plus the MEK Inhibitor Binimetinib in Patients with
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2020, 10-01, Volume: 26, Issue:19

    Topics: Adult; Aged; Alanine Transaminase; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; C

2020
Quality of life in patients with BRAF-mutant melanoma receiving the combination encorafenib plus binimetinib: Results from a multicentre, open-label, randomised, phase III study (COLUMBUS).
    European journal of cancer (Oxford, England : 1990), 2021, Volume: 152

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carb

2021
Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.
    The Lancet. Oncology, 2018, Volume: 19, Issue:5

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Biom

2018
Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multicentre, open-label, randomised, phase 3 trial.
    The Lancet. Oncology, 2018, Volume: 19, Issue:10

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Biom

2018
CI-980 in advanced melanoma and hormone refractory prostate cancer.
    Investigational new drugs, 2000, Volume: 18, Issue:2

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carbamates; Drug Resistance, Neoplasm; Female

2000
Phase II trial of CI-980 in patients with disseminated malignant melanoma and no prior chemotherapy. A Southwest Oncology Group study.
    Investigational new drugs, 2001, Volume: 19, Issue:3

    Topics: Adult; Aged; Antineoplastic Agents; Carbamates; Drug Administration Schedule; Female; Humans; Male;

2001
Initial clinical trials with 1,1-diphenyl-2-propynyl cyclohexanecarbamate (NCS-112682).
    Cancer chemotherapy reports, 1970, Volume: 54, Issue:2

    Topics: Alkynes; Antineoplastic Agents; Bone Marrow; Carbamates; Clinical Trials as Topic; Cyclohexanes; Eva

1970

Other Studies

52 other studies available for carbamates and Melanoma

ArticleYear
Switch from dabrafenib/trametinib combination therapy to encorafenib/binimetinib combination therapy with transition of serum lactate dehydrogenase level in melanoma: A case report.
    Dermatologic therapy, 2022, Volume: 35, Issue:4

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Imidazoles; Lact

2022
Conjunctival malignant melanoma treated successfully with BRAF inhibitor: encorafenib plus binimetinib.
    Dermatology online journal, 2022, 01-15, Volume: 28, Issue:1

    Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Proto-Oncogene Proteins B-raf; Sulfonamides

2022
[Efficacy of the encorafenib + binimetinib combination in a BRAF mutated metastatic melanoma case report].
    Recenti progressi in medicina, 2022, Volume: 113, Issue:6

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanoma; Mutati

2022
Development of Sesamol Carbamate-L-Phenylalanine Prodrug Targeting L-Type Amino Acid Transporter1 (LAT1) as a Potential Antiproliferative Agent against Melanoma.
    International journal of molecular sciences, 2022, Jul-30, Volume: 23, Issue:15

    Topics: Amino Acids; Benzodioxoles; Biological Transport; Carbamates; HEK293 Cells; Humans; Large Neutral Am

2022
Overcoming the resistance to BRAF inhibitor by the double BRAF and MEK inhibitions in advanced melanoma: a case report.
    Anti-cancer drugs, 2019, Volume: 30, Issue:10

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Drug Resistance, Neoplas

2019
Encorafenib and binimetinib for the treatment of BRAF-mutated metastatic melanoma in the setting of combined hepatic and renal impairment.
    BMJ case reports, 2019, Sep-16, Volume: 12, Issue:9

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Liver Neoplasms;

2019
Intracranial antitumor activity with encorafenib plus binimetinib in patients with melanoma brain metastases: A case series.
    Cancer, 2020, 02-01, Volume: 126, Issue:3

    Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Brain Neoplasms; Carbamates;

2020
Multiple Pigmented Lesions of the Breast Following Ipsilateral Breast Carcinoma.
    The American journal of medicine, 2020, Volume: 133, Issue:8

    Topics: Aged; Androstadienes; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzimi

2020
Severe pyrexia from nivolumab-resistant advanced melanoma after successful combined therapy with encorafenib plus binimetinib.
    The Journal of dermatology, 2020, Volume: 47, Issue:6

    Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Drug Resist

2020
Case of inflammatory arthritis induced by encorafenib and binimetinib in a patient with melanoma.
    The Journal of dermatology, 2020, Volume: 47, Issue:9

    Topics: Antineoplastic Combined Chemotherapy Protocols; Arthritis; Benzimidazoles; Carbamates; Humans; Melan

2020
Preclinical discovery and clinical development of encorafenib for the treatment of melanoma.
    Expert opinion on drug discovery, 2020, Volume: 15, Issue:12

    Topics: Animals; Carbamates; Drug Development; Drug Discovery; Drug Evaluation, Preclinical; Humans; Melanom

2020
Toxic epidermal necrolysis in a melanoma patient under targeted therapy with encorafenib and binimetinib.
    Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG, 2020, Volume: 18, Issue:10

    Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Stevens-Johnson Syndrome; Sulfonamides

2020
Imidazothiazole-based potent inhibitors of V600E-B-RAF kinase with promising anti-melanoma activity: biological and computational studies.
    Journal of enzyme inhibition and medicinal chemistry, 2020, Volume: 35, Issue:1

    Topics: Antineoplastic Agents; Carbamates; Cell Line, Tumor; Cell Proliferation; Drug Screening Assays, Anti

2020
Case report: acute tumour lysis syndrome following encorafenib and binimetinib for v600E metastatic melanoma with large intra-abdominal mass.
    Melanoma research, 2020, Volume: 30, Issue:6

    Topics: Acute Disease; Benzimidazoles; Carbamates; Female; Humans; Melanoma; Middle Aged; Mutation; Proto-On

2020
Stopping targeted therapy for complete responders in advanced BRAF mutant melanoma.
    Scientific reports, 2020, 11-02, Volume: 10, Issue:1

    Topics: Adult; Aged; Carbamates; Circulating Tumor DNA; Disease Progression; Female; Humans; Imidazoles; Mal

2020
Case series of BRAF-mutated advanced melanoma treated with encorafenib plus binimetinib combination therapy.
    The Journal of dermatology, 2021, Volume: 48, Issue:3

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanoma; Mutati

2021
Relatively mild symptoms after chronic overdose with a double-dose encorafenib: a case report.
    Anti-cancer drugs, 2021, 06-01, Volume: 32, Issue:5

    Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; C

2021
[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.]
    Recenti progressi in medicina, 2021, Volume: 112, Issue:4

    Topics: Aged; Benzimidazoles; Carbamates; COVID-19; Drug Combinations; Female; Humans; Melanoma; Skin Neopla

2021
Kinetics of Punctate Subretinal Deposits in Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Inhibitor-Associated Retinopathy Using En Face Optical Coherence Tomography.
    Retina (Philadelphia, Pa.), 2021, May-01, Volume: 41, Issue:5

    Topics: Acrylonitrile; Adult; Aniline Compounds; Carbamates; Extracellular Signal-Regulated MAP Kinases; Flu

2021
Cardiovascular adverse events associated with BRAF versus BRAF/MEK inhibitor: Cross-sectional and longitudinal analysis using two large national registries.
    Cancer medicine, 2021, Volume: 10, Issue:12

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocol

2021
Complete response of brainstem metastasis in BRAF-mutated melanoma without stereotactic radiosurgery after initiation of encorafenib and binimetinib.
    Melanoma research, 2021, 08-01, Volume: 31, Issue:4

    Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Brain Neoplasms; Carbamates; F

2021
Successful encorafenib desensitization in a patient with recurrent metastatic melanoma.
    Melanoma research, 2021, 08-01, Volume: 31, Issue:4

    Topics: Aged; Carbamates; Female; Humans; Melanoma; Neoplasm Recurrence, Local; Skin Neoplasms; Sulfonamides

2021
Glomerulonephritis and granulomatous vasculitis in kidney as a complication of the use of BRAF and MEK inhibitors in the treatment of metastatic melanoma: A case report.
    Medicine, 2017, Volume: 96, Issue:25

    Topics: Antineoplastic Agents; Benzimidazoles; Carbamates; Female; Glomerulonephritis; Humans; Kidney; Lung

2017
In the pipeline: encorafenib and binimetinib in BRAF-mutated melanoma.
    Clinical advances in hematology & oncology : H&O, 2017, Volume: 15, Issue:10

    Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanoma; Mutati

2017
A comparative study of the cutaneous side effects between BRAF monotherapy and BRAF/MEK inhibitor combination therapy in patients with advanced melanoma: a single-centre experience.
    European journal of dermatology : EJD, 2017, Oct-01, Volume: 27, Issue:5

    Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Imidazole

2017
PD-L1 status does not predict the outcome of BRAF inhibitor therapy in metastatic melanoma.
    European journal of cancer (Oxford, England : 1990), 2018, Volume: 88

    Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Carba

2018
Aged-looking skin and encorafenib: an adverse event of BRAF inhibitors.
    Melanoma research, 2018, Volume: 28, Issue:2

    Topics: Adult; Carbamates; Humans; Male; Melanoma; Middle Aged; Protein Kinase Inhibitors; Proto-Oncogene Pr

2018
Is there any interest in a new BRAF-MEK inhibitor combination in melanoma?
    The Lancet. Oncology, 2018, Volume: 19, Issue:5

    Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-r

2018
Encorafenib - a new agent for advanced-stage disease.
    Nature reviews. Clinical oncology, 2018, Volume: 15, Issue:6

    Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Proto-Oncogene Proteins B-raf; Sulfonamides; Vemurafen

2018
Incomplete Vogt-Koyanagi-Harada disease following treatment with encorafenib and binimetinib for metastatic melanoma.
    Melanoma research, 2018, Volume: 28, Issue:6

    Topics: Aged, 80 and over; Benzimidazoles; Carbamates; Female; Humans; Melanoma; Protein Kinase Inhibitors;

2018
Encorafenib plus binimetinib: an embarrassment of riches.
    The Lancet. Oncology, 2018, Volume: 19, Issue:10

    Topics: Benzimidazoles; Carbamates; Embarrassment; Humans; Melanoma; Proto-Oncogene Proteins B-raf; Sulfonam

2018
Integrin-targeted quantitative optoacoustic imaging with MRI correlation for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma.
    PloS one, 2018, Volume: 13, Issue:10

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Cell Line, Tumo

2018
The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B-rapidly accelerated fibrosarcoma-mutated advanced melanoma.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2019, Volume: 33, Issue:4

    Topics: Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Drug Eru

2019
Desensitization protocol for angio-oedema induced by encorafenib in a patient with metastatic melanoma.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2019, Volume: 33, Issue:7

    Topics: Carbamates; Edema; Humans; Imidazoles; Melanoma; Oximes; Sulfonamides

2019
Evaluation of cutaneous adverse events of encorafenib and binimetinb: COMMENT on article by Graf et al.
    Journal of the European Academy of Dermatology and Venereology : JEADV, 2019, Volume: 33, Issue:4

    Topics: Benzimidazoles; Carbamates; Fibrosarcoma; Humans; Melanoma; Sulfonamides

2019
Proteomic identification of a marker signature for MAPKi resistance in melanoma.
    The EMBO journal, 2019, 08-01, Volume: 38, Issue:15

    Topics: Adult; Aged; Carbamates; Cell Adhesion; Cell Line, Tumor; Disease Progression; Drug Resistance, Neop

2019
Eruptive naevi in a patient treated with LGX818 for BRAF mutant metastatic melanoma.
    Melanoma research, 2015, Volume: 25, Issue:1

    Topics: Antineoplastic Agents; Carbamates; Dermatology; Dermoscopy; Humans; Male; Melanoma; Middle Aged; Mut

2015
PI3'-kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAF-mutated melanoma.
    Cancer discovery, 2015, Volume: 5, Issue:2

    Topics: Animals; Carbamates; Cell Line, Tumor; Cell Proliferation; Humans; MAP Kinase Kinase 1; MAP Kinase K

2015
Game of isoforms: PI3K β-sparing inhibitor is coming.
    Pigment cell & melanoma research, 2015, Volume: 28, Issue:2

    Topics: Animals; Carbamates; Humans; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Melanoma; Protein Kinase Inhi

2015
Clinical observation of panniculitis in two patients with BRAF-mutated metastatic melanoma treated with a combination of a BRAF inhibitor and a MEK inhibitor.
    European journal of dermatology : EJD, 2015, Volume: 25, Issue:2

    Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Imidazole

2015
Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells.
    Cancer letters, 2016, Jan-28, Volume: 370, Issue:2

    Topics: Autophagy; Carbamates; Cell Line, Tumor; Cellular Senescence; Cyclin D1; Cyclin-Dependent Kinase Inh

2016
BRAF V600 inhibitor discontinuation after complete response in advanced melanoma: a retrospective analysis of 16 patients.
    The British journal of dermatology, 2017, Volume: 177, Issue:4

    Topics: Adult; Antineoplastic Agents; Carbamates; Drug Substitution; Humans; Imidazoles; Indoles; Melanoma;

2017
Melanocyte-Directed enzyme prodrug therapy (MDEPT): development of second generation prodrugs for targeted treatment of malignant melanoma.
    Bioorganic & medicinal chemistry, 2001, Volume: 9, Issue:6

    Topics: Agaricales; Carbamates; Daunorubicin; Drug Design; Drug Evaluation, Preclinical; Humans; Melanocytes

2001
Nocodazole, a new synthetic antimitotic agent, enhances the production of plasminogen activator by cells in culture.
    Thrombosis research, 1977, Volume: 11, Issue:6

    Topics: Animals; Benzimidazoles; Carbamates; Cells, Cultured; Melanoma; Mice; Mitosis; Plasminogen Activator

1977
The effects of methyl (5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl) carbamate, (R 17934; NSC 238159), a new synthetic antitumoral drug interfering with microtubules, on mammalian cells cultured in vitro.
    Cancer research, 1976, Volume: 36, Issue:3

    Topics: Antineoplastic Agents; Benzimidazoles; Carbamates; Cell Line; Colchicine; Cytoplasm; Fibrosarcoma; H

1976
The tyrosinase activity of melanosomes from the Harding-Passey melanoma: the absence of a peroxidase component in vitro.
    Archives of biochemistry and biophysics, 1975, Volume: 167, Issue:2

    Topics: Animals; Carbamates; Catechol Oxidase; Cytoplasmic Granules; Melanins; Melanoma; Mice; Mice, Inbred

1975
R17934-NSC 238159: a new antitumor drug--I. Effect on experimental tumors and factors influencing effectiveness.
    European journal of cancer, 1975, Volume: 11, Issue:9

    Topics: Animals; Antineoplastic Agents; Benzimidazoles; Carbamates; Ependymoma; Leukemia L1210; Leukemia, Ex

1975
Initial clinical studies with copovithane.
    Journal of biological response modifiers, 1986, Volume: 5, Issue:4

    Topics: Adult; Aged; Antineoplastic Agents; Carbamates; Cytotoxicity, Immunologic; Drug Evaluation; Drug Tol

1986
Pharmacokinetics and tissue disposition of the biological response modifier BAY i 7433 (copovithane) in patients with cancer.
    Cancer chemotherapy and pharmacology, 1986, Volume: 18, Issue:3

    Topics: Antineoplastic Agents; Biopsy; Carbamates; Chromatography, High Pressure Liquid; Drug Evaluation; Hu

1986
Subcellular demonstration of peroxidatic oxidation of tyrosine to melanin using dihydroxyfumarate as cofactor in mouse melanoma cells.
    The Journal of investigative dermatology, 1973, Volume: 61, Issue:2

    Topics: Amines; Animals; Biphenyl Compounds; Carbamates; Dihydroxyphenylalanine; Endoplasmic Reticulum; Fuma

1973
Effect of inhibitors on phenoloxidase of Mycobacterium leprae.
    Journal of bacteriology, 1969, Volume: 100, Issue:2

    Topics: Antimetabolites; Basidiomycota; Carbamates; Catechol Oxidase; Dihydroxyphenylalanine; Enzyme Repress

1969
The tyrosine hydroxylase activity of mammalian tyrosinase.
    The Journal of biological chemistry, 1966, Jan-10, Volume: 241, Issue:1

    Topics: 5-Hydroxytryptophan; Animals; Ascorbic Acid; Carbamates; Cricetinae; Cyanides; Dihydroxyphenylalanin

1966