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)
Excerpt | Relevance | Reference |
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"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." | 9.41 | 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). ( 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)." | 9.34 | 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. ( 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." | 9.05 | Safety 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." | 9.05 | An 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." | 8.98 | Development 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." | 8.12 | Development 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." | 8.02 | Case 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." | 7.96 | Preclinical 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." | 7.96 | Intracranial 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." | 7.96 | Severe 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." | 7.91 | The 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." | 7.88 | Incomplete 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." | 5.62 | Complete 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." | 5.43 | Encorafenib (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." | 5.41 | 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). ( 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)." | 5.34 | 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. ( 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." | 5.30 | Adverse 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." | 5.05 | An 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." | 5.05 | Safety 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." | 4.98 | Development 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." | 4.12 | Development 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." | 4.02 | Case 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)." | 4.02 | Relatively 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." | 3.96 | Preclinical 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." | 3.96 | Severe 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." | 3.96 | Intracranial 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." | 3.91 | The 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." | 3.88 | Incomplete 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." | 3.88 | Integrin-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." | 3.81 | Clinical 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." | 2.82 | 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. ( 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." | 2.70 | Phase 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." | 1.62 | Cardiovascular 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." | 1.62 | Complete 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." | 1.43 | Encorafenib (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) |
Timeframe | Studies, this research(%) | All Research% |
---|---|---|
pre-1990 | 10 (13.51) | 18.7374 |
1990's | 0 (0.00) | 18.2507 |
2000's | 3 (4.05) | 29.6817 |
2010's | 32 (43.24) | 24.3611 |
2020's | 29 (39.19) | 2.80 |
Authors | Studies |
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Sato, T | 1 |
Noto, M | 1 |
Yamada, M | 1 |
Kono, M | 1 |
Schadendorf, D | 7 |
Dummer, R | 11 |
Robert, C | 7 |
Ribas, A | 1 |
Sullivan, RJ | 2 |
Panella, T | 1 |
McKean, M | 1 |
Santos, ES | 1 |
Brill, K | 1 |
Polli, A | 1 |
Pietro, AD | 1 |
Ascierto, PA | 8 |
Miura, S | 1 |
Onishi, M | 1 |
Watabe, D | 1 |
Amano, H | 1 |
Di Guardo, L | 1 |
Srisongkram, T | 1 |
Bahrami, K | 1 |
Järvinen, J | 1 |
Timonen, J | 1 |
Rautio, J | 1 |
Weerapreeyakul, N | 1 |
Corrie, P | 1 |
Meyer, N | 2 |
Berardi, R | 1 |
Guidoboni, M | 1 |
Schlueter, M | 1 |
Kolovos, S | 1 |
Macabeo, B | 1 |
Trouiller, JB | 1 |
Laramée, P | 1 |
Gogas, HJ | 4 |
Flaherty, KT | 5 |
Arance, A | 5 |
Mandala, M | 6 |
Liszkay, G | 5 |
Garbe, C | 6 |
Krajsova, I | 5 |
Gutzmer, R | 6 |
Sileni, VC | 2 |
Dutriaux, C | 4 |
de Groot, JWB | 4 |
Yamazaki, N | 4 |
Loquai, C | 5 |
Gollerkeri, A | 3 |
Pickard, MD | 5 |
Kattan, J | 1 |
Kattan, C | 1 |
Farhat, F | 1 |
Assi, T | 1 |
Ngo, P | 1 |
Bycroft, R | 1 |
Holbrook, K | 1 |
Lutzky, J | 1 |
Davies, MA | 1 |
Davis, JM | 1 |
Glitza, IC | 1 |
Amaria, RN | 1 |
Diab, A | 1 |
Patel, SP | 1 |
Amin, A | 1 |
Tawbi, H | 1 |
Carr, MJ | 1 |
Sun, J | 1 |
Eroglu, Z | 2 |
Zager, JS | 1 |
Limmer, A | 1 |
Swali, R | 1 |
Robare, S | 1 |
Specenier, P | 1 |
Amagai, R | 2 |
Fujimura, T | 2 |
Kambayashi, Y | 2 |
Sato, Y | 1 |
Tanita, K | 1 |
Ohuchi, K | 2 |
Hashimoto, A | 2 |
Aiba, S | 2 |
Matsudate, Y | 1 |
Weber, J | 1 |
Patel, S | 1 |
Carlino, MS | 1 |
Tan, DSW | 1 |
Lebbé, C | 1 |
Siena, S | 1 |
Elez, E | 1 |
Wollenberg, L | 1 |
Sandor, V | 3 |
Okten, IN | 1 |
Ismail, S | 1 |
Withycombe, BM | 1 |
Lang, N | 1 |
Schinaia, CG | 1 |
Wolfsperger, F | 1 |
Schaller, M | 1 |
Forchhammer, S | 1 |
Forschner, A | 1 |
Indini, A | 1 |
Anbar, HS | 1 |
El-Gamal, MI | 1 |
Tarazi, H | 1 |
Lee, BS | 1 |
Jeon, HR | 1 |
Kwon, D | 1 |
Oh, CH | 1 |
Byron, Y | 1 |
Nott, L | 1 |
Shackleton, M | 1 |
Warburton, L | 1 |
Meniawy, TM | 1 |
Calapre, L | 1 |
Pereira, M | 1 |
McEvoy, A | 1 |
Ziman, M | 1 |
Gray, ES | 1 |
Millward, M | 1 |
Yoshino, K | 1 |
Kato, H | 1 |
Fujisawa, Y | 1 |
Nakamura, Y | 1 |
Yamamoto, Y | 1 |
Kunimoto, K | 1 |
Ito, T | 1 |
Matsushita, S | 1 |
Maekawa, T | 1 |
Muto, Y | 1 |
Furudate, S | 1 |
Mian, P | 1 |
Meussen, E | 1 |
Piersma, D | 1 |
Lankheet, NAG | 1 |
Sibaud, V | 1 |
Baric, L | 1 |
Cantagrel, A | 1 |
Di Palma, M | 1 |
Ederhy, S | 1 |
Paques, M | 1 |
Perlemuter, G | 1 |
Spagnolo, F | 1 |
Ramtohul, P | 1 |
Denis, D | 1 |
Comet, A | 1 |
Guha, A | 1 |
Jain, P | 1 |
Fradley, MG | 1 |
Lenihan, D | 1 |
Gutierrez, JM | 1 |
Jain, C | 1 |
de Lima, M | 1 |
Barnholtz-Sloan, JS | 1 |
Oliveira, GH | 1 |
Dowlati, A | 1 |
Al-Kindi, S | 1 |
Khullar, K | 1 |
Hanft, S | 1 |
Mehnert, JM | 1 |
Weiner, JP | 1 |
Gogas, H | 2 |
Queirolo, P | 1 |
Jan de Willem, G | 1 |
Sellier, AT | 1 |
Suissa, J | 1 |
Murris, J | 1 |
Cullen, GD | 1 |
Finnes, HD | 1 |
Markovic, SN | 1 |
Volcheck, GW | 1 |
Daud, A | 1 |
Tsai, K | 1 |
Maanaoui, M | 1 |
Saint-Jacques, C | 1 |
Gnemmi, V | 1 |
Frimat, M | 1 |
Lionet, A | 1 |
Hazzan, M | 1 |
Noël, C | 1 |
Provot, F | 1 |
Flaherty, K | 1 |
Russo, I | 1 |
Zorzetto, L | 1 |
Frigo, AC | 1 |
Chiarion Sileni, V | 2 |
Alaibac, M | 1 |
Schaper-Gerhardt, K | 1 |
Okoye, S | 1 |
Herbst, R | 1 |
Ulrich, J | 1 |
Terheyden, P | 1 |
Pföhler, C | 1 |
Utikal, JS | 1 |
Kreuter, A | 1 |
Mohr, P | 1 |
Dippel, E | 1 |
Satzger, I | 1 |
Sucker, A | 1 |
Ugurel, S | 1 |
Koelblinger, P | 2 |
Thuerigen, O | 1 |
Fernández-Sartorio, C | 1 |
Boada, A | 1 |
Chavez-Bourgeois, MM | 1 |
Ruiz Ares, GJ | 1 |
Arance, AM | 1 |
Manzano, JL | 1 |
García-Herrera, A | 1 |
Carrera, C | 1 |
Grob, JJ | 1 |
Chiarion-Sileni, V | 1 |
Moutouh-de Parseval, LA | 2 |
Sidaway, P | 1 |
Shirley, M | 1 |
Diamantopoulos, PT | 1 |
Stoungioti, S | 1 |
Anastasopoulou, A | 1 |
Papaxoinis, G | 1 |
Martin-Liberal, J | 1 |
Kazmierczak, PM | 1 |
Burton, NC | 1 |
Keinrath, G | 1 |
Hirner-Eppeneder, H | 1 |
Schneider, MJ | 1 |
Eschbach, RS | 1 |
Heimer, M | 1 |
Solyanik, O | 1 |
Todica, A | 1 |
Reiser, MF | 1 |
Ricke, J | 1 |
Cyran, CC | 1 |
Graf, NP | 1 |
Galliker, N | 1 |
Conrad, S | 1 |
Barysch, M | 1 |
Mangana, J | 2 |
Cheng, PF | 2 |
Goldinger, SM | 2 |
Trojaniello, C | 1 |
Festino, L | 1 |
Vanella, V | 1 |
Brue, A | 1 |
Benzaquen, M | 1 |
Bonnet, N | 1 |
Koeppel, MC | 1 |
Default, A | 1 |
Delaporte, E | 1 |
Berbis, P | 1 |
Livingstone, E | 1 |
Rose, AAN | 1 |
Paulitschke, V | 1 |
Eichhoff, O | 1 |
Gerner, C | 1 |
Paulitschke, P | 1 |
Bileck, A | 1 |
Mohr, T | 1 |
Leitner, A | 1 |
Guenova, E | 1 |
Saulite, I | 1 |
Freiberger, SN | 1 |
Irmisch, A | 1 |
Knapp, B | 1 |
Zila, N | 1 |
Chatziisaak, TP | 1 |
Stephan, J | 1 |
Kunstfeld, R | 1 |
Pehamberger, H | 1 |
Aebersold, R | 1 |
Levesque, MP | 1 |
Anforth, RM | 1 |
Carlos, GR | 1 |
Scolyer, RA | 1 |
Chou, S | 1 |
Fernandez-Peñas, P | 1 |
Deuker, MM | 1 |
Marsh Durban, V | 1 |
Phillips, WA | 1 |
McMahon, M | 1 |
Cheng, H | 1 |
Aplin, AE | 1 |
Galliker, NA | 1 |
Murer, C | 1 |
Kamarashev, J | 1 |
Li, Z | 1 |
Jiang, K | 1 |
Zhu, X | 1 |
Lin, G | 1 |
Song, F | 1 |
Zhao, Y | 1 |
Piao, Y | 1 |
Liu, J | 1 |
Cheng, W | 1 |
Bi, X | 1 |
Gong, P | 1 |
Song, Z | 1 |
Meng, S | 1 |
Vanhaecke, C | 1 |
Deilhes, F | 1 |
Chanal, J | 1 |
Regnier-Rosencher, E | 1 |
Boitier, F | 1 |
Boulinguez, S | 1 |
Avril, MF | 1 |
Guégan, S | 1 |
Dupin, N | 1 |
Aractingi, S | 1 |
Kramkimel, N | 1 |
Turner, MC | 1 |
Rossfeld, K | 1 |
Salama, AK | 1 |
Tyler, D | 1 |
Beasley, G | 1 |
Ryan, CW | 1 |
Shulman, KL | 1 |
Richards, JM | 1 |
Kugler, JW | 1 |
Sosman, JA | 1 |
Ansari, RH | 1 |
Vokes, EE | 1 |
Vogelzang, NJ | 1 |
Jordan, AM | 1 |
Khan, TH | 1 |
Malkin, H | 1 |
Osborn, HM | 1 |
Photiou, A | 1 |
Riley, PA | 1 |
Whitehead, RP | 1 |
Unger, JM | 1 |
Flaherty, LE | 1 |
Eckardt, JR | 1 |
Taylor, SA | 1 |
Didolkar, MS | 1 |
Samlowski, W | 1 |
Sondak, VK | 1 |
De Clerck, F | 1 |
De Brabander, M | 1 |
De Brabander, MJ | 1 |
Van de Veire, RM | 1 |
Aerts, FE | 1 |
Borgers, M | 1 |
Janssen, PA | 1 |
Mufson, RA | 1 |
Atassi, G | 1 |
Tagnon, HJ | 1 |
Hortobagyi, GN | 2 |
Hersh, EM | 1 |
Papadopoulos, NE | 1 |
Frye, D | 1 |
Rios, A | 1 |
Reuben, JM | 1 |
Plager, C | 1 |
Rosenblum, M | 1 |
Quesada, J | 1 |
Rosenblum, MG | 1 |
Okun, MR | 1 |
Donnellan, B | 1 |
Patel, RP | 1 |
Edelstein, LM | 1 |
Luce, JK | 1 |
Bodey, GP | 1 |
Prabhakaran, K | 1 |
Harris, EB | 1 |
Kirchheimer, WF | 1 |
Pomerantz, SH | 1 |
Trial | Phase | Enrollment | Study Type | Start Date | Status | ||
---|---|---|---|---|---|---|---|
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 3 | 624 participants (Anticipated) | Interventional | 2021-01-15 | Recruiting | ||
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 3 | 921 participants (Actual) | Interventional | 2013-12-13 | Active, 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 2 | 78 participants (Anticipated) | Interventional | 2020-06-04 | Recruiting | ||
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 2 | 189 participants (Actual) | Interventional | 2012-05-28 | Completed | ||
[information is prepared from clinicaltrials.gov, extracted Sep-2024] |
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)
Intervention | percentage of participants (Number) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 92.2 |
Part 1: LGX818 300 mg | 84.0 |
Part 1: Vemurafenib 960 mg BID | 81.7 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 90.7 |
Part 2: LGX818 300 mg | 79.1 |
Part 1 + Part 2: LGX818 300 mg | 82.5 |
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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 16.6 |
Part 1: LGX818 300 mg | 15.2 |
Part 1: Vemurafenib 960 mg BID | 12.3 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 12.7 |
Part 2: LGX818 300 mg | 7.5 |
Part 1 + Part 2: LGX818 300 mg | 12.9 |
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)
Intervention | percentage of participants (Number) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 63.0 |
Part 1: LGX818 300 mg | 50.5 |
Part 1: Vemurafenib 960 mg BID | 40.3 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 65.9 |
Part 2: LGX818 300 mg | 50.0 |
Part 1 + Part 2: LGX818 300 mg | 50.4 |
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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | NA |
Part 1: LGX818 300 mg | 26.7 |
Part 1: Vemurafenib 960 mg BID | 18.2 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | NA |
Part 2: LGX818 300 mg | 10.2 |
Part 1 + Part 2: LGX818 300 mg | 19.2 |
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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | NA |
Part 1: LGX818 300 mg | 30.5 |
Part 1: Vemurafenib 960 mg BID | 22.1 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | NA |
Part 2: LGX818 300 mg | NA |
Part 1 + Part 2: LGX818 300 mg | 20.5 |
"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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 23.9 |
Part 1: LGX818 300 mg | 14.7 |
Part 1: Vemurafenib 960 mg BID | 16.6 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 18.4 |
Part 2: LGX818 300 mg | 9.5 |
Part 1 + Part 2: LGX818 300 mg | 11.1 |
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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 1.9 |
Part 1: LGX818 300 mg | 2.0 |
Part 1: Vemurafenib 960 mg BID | 2.1 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 1.9 |
Part 2: LGX818 300 mg | 1.9 |
Part 1 + Part 2: LGX818 300 mg | 1.9 |
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
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 14.9 |
Part 1: LGX818 300 mg | 9.6 |
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)
Intervention | months (Median) |
---|---|
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 14.9 |
Part 1: Vemurafenib 960 mg BID | 7.3 |
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)
Intervention | months (Median) |
---|---|
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 12.9 |
Part 2: LGX818 300 mg | 7.4 |
Part 1 + Part 2: LGX818 300 mg | 9.2 |
"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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 74.20 | 1.79 | 2.96 | -3.62 | -0.60 | -2.69 | -6.41 | -2.12 | 1.79 | 2.78 | 16.67 | 5.56 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 73.04 | 7.29 | 6.15 | 9.37 | 9.22 | 10.56 | 8.66 | 10.59 | 10.33 | 8.33 | 13.13 | -4.17 |
"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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 74.38 | 0.32 | 1.98 | -0.91 | 1.26 | -0.74 | 0.83 | 1.30 | 3.26 | 1.27 | -0.76 | 2.94 | -0.32 | -0.83 |
Part 1: LGX818 300 mg | 74.46 | -0.34 | 1.54 | 0.34 | 2.15 | 0.12 | 3.78 | 2.30 | 3.64 | 1.00 | -1.16 | 2.94 | -0.32 | -3.57 |
Part 1: Vemurafenib 960 mg BID | 72.31 | 1.88 | 2.03 | 2.71 | -0.17 | 4.53 | -2.25 | -5.46 | -1.39 | 0.38 | -3.13 | -0.69 | -1.19 | 12.50 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 74.68 | 3.23 | 5.37 | 5.42 | 4.47 | 4.81 | 3.52 | 7.35 | 5.33 | 4.25 | 4.17 | -1.74 | 3.92 | 41.67 |
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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 0.73 | -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) | 0.75 | 0.06 | 0.07 | 0.06 | 0.07 | 0.06 | 0.05 | 0.05 | 0.06 | 0.05 | 0.12 | -0.27 |
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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 0.75 | -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 mg | 0.76 | -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 BID | 0.73 | 0.00 | -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) | 0.74 | 0.05 | 0.04 | 0.05 | 0.03 | 0.04 | 0.05 | 0.05 | 0.07 | 0.03 | 0.07 | 0.04 | 0.07 | 0.03 |
"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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 67.39 | -4.95 | -4.72 | -7.08 | -8.73 | -7.53 | -9.29 | -12.75 | -7.14 | -0.93 | 0.00 | 4.17 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 65.95 | 4.47 | 5.61 | 5.01 | 4.94 | 4.76 | 5.89 | 6.11 | 5.86 | 1.23 | 3.03 | -6.25 |
"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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 66.48 | -6.81 | -7.87 | -8.53 | -10.96 | -10.13 | -8.80 | -10.56 | -7.85 | -8.05 | -10.80 | -5.64 | -7.05 | 4.63 |
Part 1: LGX818 300 mg | 66.07 | -7.64 | -9.24 | -9.21 | -12.03 | -11.27 | -8.59 | -9.91 | -8.03 | -9.33 | -11.05 | -5.64 | -7.05 | 4.76 |
Part 1: Vemurafenib 960 mg BID | 64.74 | -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) | 66.72 | 3.56 | 1.55 | 1.53 | -0.55 | 0.81 | 0.42 | 5.02 | 0.41 | -0.51 | 0.74 | -1.39 | 1.96 | 0.00 |
"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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 81.45 | -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) | 80.67 | 2.94 | 2.73 | 1.22 | 3.03 | 0.50 | 0.47 | -0.40 | -0.88 | -5.71 | -8.48 | -5.00 |
"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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 82.63 | -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 mg | 83.18 | -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 BID | 80.71 | -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) | 82.10 | 0.20 | 0.15 | -1.93 | -0.45 | -0.85 | -1.25 | 0.29 | -0.03 | -1.22 | -0.95 | -5.00 | -5.49 | 33.33 |
"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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 78.31 | -10.00 | -5.11 | -13.89 | -9.52 | -12.37 | -5.77 | -15.69 | -7.14 | -12.96 | -33.33 | 0.00 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 81.37 | 4.05 | 3.37 | 3.05 | 3.66 | 1.95 | 1.75 | 2.86 | 1.59 | 1.23 | 4.55 | -16.67 |
"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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1 + Part 2: LGX818 300 mg | 80.09 | -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 mg | 80.91 | -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 BID | 78.54 | -4.90 | -7.21 | -2.75 | -1.99 | -0.36 | -0.45 | -6.32 | 1.39 | 3.79 | -3.13 | 1.39 | 4.76 | -8.33 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 80.69 | -0.66 | 3.26 | 2.82 | 1.57 | -2.72 | -4.27 | 3.73 | 1.11 | -1.04 | -1.52 | -12.32 | -5.21 | 25.00 |
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)
Intervention | units on a scale (Mean) | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at End of treatment visit | |
Part 2: LGX818 300 mg | 51.13 | -2.16 | -0.60 | -3.14 | -1.83 | -2.41 | -3.31 | -4.14 | -2.64 | 0.00 | -2.00 | -1.61 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 52.08 | 2.79 | 2.58 | 2.64 | 3.23 | 2.54 | 1.97 | 2.08 | 2.45 | 1.23 | 2.58 | 6.58 |
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)
Intervention | units on a scale (Mean) | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline | Change at Cycle 3 Day 1 | Change at Cycle 5 Day 1 | Change at Cycle 7 Day 1 | Change at Cycle 9 Day 1 | Change at Cycle 11 Day 1 | Change at Cycle 13 Day 1 | Change at Cycle 15 Day 1 | Change at Cycle 17 Day 1 | Change at Cycle 19 Day 1 | Change at Cycle 21 Day 1 | Change at Cycle 23 Day 1 | Change at Cycle 25 Day 1 | Change at End of treatment visit | |
Part 1: Vemurafenib 960 mg BID | 52.01 | -1.55 | -1.90 | -2.19 | -1.90 | -0.51 | -0.97 | -1.72 | 0.70 | 0.23 | -3.33 | -0.17 | -0.14 | -2.31 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 52.39 | 0.92 | -0.01 | 1.35 | 0.52 | 0.18 | -0.33 | 0.40 | 0.27 | -0.59 | -0.69 | -1.67 | -1.83 | 18.50 |
Part 1 + Part 2: LGX818 300 mg | 52.24 | -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 mg | 52.76 | -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 |
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)
Intervention | Participants (Count of Participants) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Baseline: ECOG score 0 | Baseline: ECOG score 1 | Cycle 2 Day 1: ECOG score 0 | Cycle 2 Day 1: ECOG score 1 | Cycle 2 Day 1: ECOG score 2 | Cycle 2 Day 1: ECOG score 3 | Cycle 2 Day 1: ECOG score 4 | Cycle 3 Day 1: ECOG score 0 | Cycle 3 Day 1: ECOG score 1 | Cycle 3 Day 1: ECOG score 2 | Cycle 4 Day 1: ECOG score 0 | Cycle 4 Day 1: ECOG score 1 | Cycle 4 Day 1: ECOG score 2 | Cycle 4 Day 1: ECOG score 3 | Cycle 5 Day 1: ECOG score 0 | Cycle 5 Day 1: ECOG score 1 | Cycle 5 Day 1: ECOG score 2 | Cycle 5 Day 1: ECOG score 3 | Cycle 5 Day 1: ECOG score 4 | Cycle 6 Day 1: ECOG score 0 | Cycle 6 Day 1: ECOG score 1 | Cycle 6 Day 1: ECOG score 2 | Cycle 6 Day 1: ECOG score 3 | Cycle 6 Day 1: ECOG score 4 | Cycle 7 Day 1: ECOG score 0 | Cycle 7 Day 1: ECOG score 1 | Cycle 7 Day 1: ECOG score 2 | Cycle 8 Day 1: ECOG score 0 | Cycle 8 Day 1: ECOG score 1 | Cycle 8 Day 1: ECOG score 2 | Cycle 8 Day 1: ECOG score 3 | Cycle 9 Day 1: ECOG score 0 | Cycle 9 Day 1: ECOG score 1 | Cycle 9 Day 1: ECOG score 2 | Cycle 9 Day 1: ECOG score 3 | Cycle 9 Day 1: ECOG score 4 | Cycle 9 Day 1: ECOG score 5 | Cycle 10 Day 1: ECOG score 0 | Cycle 10 Day 1: ECOG score 1 | Cycle 10 Day 1: ECOG score 2 | Cycle 10 Day 1: ECOG score 3 | Cycle 11 Day 1: ECOG score 0 | Cycle 11 Day 1: ECOG score 1 | Cycle 11 Day 1: ECOG score 2 | Cycle 11 Day 1: ECOG score 3 | Cycle 12 Day 1: ECOG score 0 | Cycle 12 Day 1: ECOG score 1 | Cycle 12 Day 1: ECOG score 2 | Cycle 12 Day 1: ECOG score 3 | Cycle 12 Day 1: ECOG score 4 | Cycle 13 Day 1: ECOG score 0 | Cycle 13 Day 1: ECOG score 1 | Cycle 13 Day 1: ECOG score 2 | Cycle 13 Day 1: ECOG score 4 | Cycle 14 Day 1: ECOG score 0 | Cycle 14 Day 1: ECOG score 1 | Cycle 14 Day 1: ECOG score 2 | Cycle 14 Day 1: ECOG score 3 | Cycle 14 Day 1: ECOG score 4 | Cycle 15 Day 1: ECOG score 0 | Cycle 15 Day 1: ECOG score 1 | Cycle 15 Day 1: ECOG score 2 | Cycle 15 Day 1: ECOG score 3 | Cycle 15 Day 1: ECOG score 4 | Cycle 16 Day 1: ECOG score 0 | Cycle 16 Day 1: ECOG score 1 | Cycle 16 Day 1: ECOG score 2 | Cycle 16 Day 1: ECOG score 3 | Cycle 17 Day 1: ECOG score 0 | Cycle 17 Day 1: ECOG score 1 | Cycle 17 Day 1: ECOG score 2 | Cycle 18 Day 1: ECOG score 0 | Cycle 18 Day 1: ECOG score 1 | Cycle 18 Day 1: ECOG score 2 | Cycle 18 Day 1: ECOG score 3 | Cycle 19 Day 1: ECOG score 0 | Cycle 19 Day 1: ECOG score 1 | Cycle 19 Day 1: ECOG score 2 | Cycle 20 Day 1: ECOG score 0 | Cycle 20 Day 1: ECOG score 1 | Cycle 20 Day 1: ECOG score 2 | Cycle 20 Day 1: ECOG score 3 | Cycle 21 Day 1: ECOG score 0 | Cycle 21 Day 1: ECOG score 1 | Cycle 21 Day 1: ECOG score 2 | Cycle 22 Day 1: ECOG score 0 | Cycle 22 Day 1: ECOG score 1 | Cycle 22 Day 1: ECOG score 3 | Cycle 22 Day 1: ECOG score 4 | Cycle 23 Day 1: ECOG score 0 | Cycle 23 Day 1: ECOG score 1 | Cycle 24 Day 1: ECOG score 0 | Cycle 24 Day 1: ECOG score 1 | Cycle 25 Day 1: ECOG score 0 | Cycle 25 Day 1: ECOG score 1 | Cycle 26 Day 1: ECOG score 0 | Cycle 26 Day 1: ECOG score 1 | Cycle 26 Day 1: ECOG score 2 | Cycle 27 Day 1: ECOG score 0 | Cycle 27 Day 1: ECOG score 1 | Cycle 28 Day 1: ECOG score 0 | Cycle 28 Day 1: ECOG score 1 | Cycle 29 Day 1: ECOG score 0 | Cycle 29 Day 1: ECOG score 1 | Cycle 30 Day 1: ECOG score 0 | Cycle 30 Day 1: ECOG score 1 | Cycle 31 Day 1: ECOG score 0 | Cycle 31 Day 1: ECOG score 1 | |
Part 1 + Part 2: LGX818 300 mg | 199 | 77 | 142 | 111 | 7 | 2 | 0 | 130 | 113 | 6 | 128 | 96 | 7 | 1 | 118 | 100 | 6 | 0 | 0 | 97 | 90 | 6 | 1 | 1 | 95 | 87 | 2 | 77 | 70 | 6 | 1 | 72 | 67 | 1 | 1 | 0 | 0 | 70 | 53 | 2 | 0 | 61 | 56 | 4 | 0 | 55 | 49 | 2 | 1 | 0 | 55 | 46 | 3 | 0 | 62 | 37 | 2 | 0 | 1 | 54 | 37 | 2 | 0 | 0 | 52 | 30 | 4 | 0 | 48 | 33 | 2 | 41 | 29 | 0 | 0 | 40 | 26 | 1 | 34 | 22 | 2 | 0 | 31 | 20 | 1 | 27 | 16 | 1 | 1 | 26 | 12 | 23 | 10 | 23 | 8 | 21 | 8 | 0 | 20 | 6 | 18 | 6 | 13 | 5 | 9 | 3 | 7 | 3 |
Part 1: LGX818 300 mg | 139 | 53 | 98 | 79 | 3 | 2 | 0 | 90 | 81 | 4 | 93 | 66 | 4 | 1 | 85 | 69 | 4 | 0 | 0 | 68 | 65 | 3 | 0 | 1 | 68 | 60 | 1 | 55 | 49 | 3 | 1 | 50 | 47 | 1 | 0 | 0 | 0 | 52 | 35 | 1 | 0 | 44 | 40 | 1 | 0 | 44 | 31 | 1 | 1 | 0 | 41 | 31 | 1 | 0 | 47 | 27 | 0 | 0 | 1 | 41 | 30 | 1 | 0 | 0 | 41 | 23 | 3 | 0 | 39 | 27 | 1 | 36 | 24 | 0 | 0 | 38 | 20 | 1 | 31 | 19 | 2 | 0 | 29 | 19 | 1 | 27 | 16 | 1 | 1 | 26 | 12 | 23 | 10 | 23 | 8 | 21 | 8 | 0 | 20 | 6 | 18 | 6 | 13 | 5 | 9 | 3 | 7 | 3 |
Part 1: Vemurafenib 960 mg BID | 135 | 51 | 113 | 64 | 4 | 0 | 0 | 107 | 64 | 4 | 98 | 52 | 4 | 4 | 82 | 52 | 7 | 1 | 1 | 78 | 46 | 1 | 1 | 0 | 74 | 35 | 2 | 58 | 33 | 4 | 0 | 55 | 30 | 4 | 1 | 0 | 0 | 43 | 26 | 2 | 1 | 39 | 20 | 2 | 1 | 32 | 16 | 2 | 1 | 0 | 27 | 18 | 2 | 0 | 25 | 19 | 2 | 0 | 0 | 22 | 18 | 1 | 0 | 0 | 24 | 10 | 1 | 0 | 21 | 11 | 1 | 18 | 11 | 1 | 1 | 20 | 9 | 1 | 19 | 8 | 0 | 0 | 15 | 8 | 0 | 11 | 6 | 0 | 0 | 10 | 5 | 9 | 5 | 9 | 2 | 7 | 2 | 0 | 3 | 4 | 4 | 1 | 5 | 0 | 4 | 0 | 2 | 0 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 136 | 56 | 142 | 44 | 1 | 0 | 1 | 131 | 53 | 1 | 128 | 50 | 1 | 0 | 128 | 42 | 3 | 1 | 0 | 124 | 45 | 0 | 0 | 0 | 111 | 46 | 1 | 112 | 33 | 2 | 1 | 102 | 36 | 4 | 0 | 1 | 1 | 94 | 32 | 3 | 0 | 88 | 30 | 2 | 0 | 84 | 25 | 1 | 0 | 0 | 77 | 22 | 1 | 0 | 74 | 23 | 0 | 0 | 0 | 72 | 20 | 1 | 1 | 0 | 64 | 24 | 1 | 0 | 65 | 16 | 1 | 60 | 14 | 1 | 0 | 54 | 9 | 2 | 53 | 7 | 0 | 1 | 36 | 10 | 9 | 29 | 8 | 0 | 0 | 24 | 6 | 21 | 7 | 17 | 3 | 14 | 3 | 1 | 5 | 3 | 5 | 3 | 1 | 2 | 0 | 0 | 0 | 0 |
Part 2: LGX818 300 mg | 60 | 24 | 44 | 32 | 4 | 0 | 0 | 40 | 32 | 2 | 35 | 30 | 3 | 0 | 33 | 31 | 2 | 0 | 0 | 29 | 25 | 3 | 1 | 0 | 27 | 27 | 1 | 22 | 21 | 3 | 0 | 22 | 20 | 0 | 1 | 0 | 0 | 18 | 18 | 1 | 0 | 17 | 16 | 3 | 0 | 11 | 18 | 1 | 0 | 0 | 14 | 15 | 2 | 0 | 15 | 10 | 2 | 0 | 0 | 13 | 7 | 1 | 0 | 0 | 11 | 7 | 1 | 0 | 9 | 6 | 1 | 5 | 5 | 0 | 0 | 2 | 6 | 0 | 3 | 3 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 189 | 68 | 193 | 62 | 1 | 0 | 0 | 197 | 55 | 1 | 189 | 56 | 4 | 1 | 181 | 55 | 2 | 1 | 0 | 168 | 58 | 3 | 1 | 1 | 158 | 58 | 2 | 140 | 58 | 1 | 1 | 135 | 52 | 0 | 0 | 1 | 0 | 121 | 46 | 3 | 1 | 116 | 42 | 0 | 0 | 113 | 38 | 0 | 0 | 1 | 102 | 39 | 1 | 1 | 100 | 33 | 2 | 1 | 0 | 82 | 27 | 1 | 0 | 1 | 64 | 23 | 0 | 1 | 52 | 15 | 1 | 34 | 11 | 1 | 0 | 22 | 7 | 1 | 15 | 5 | 0 | 0 | 11 | 2 | 0 | 4 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 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 4.03 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
Intervention | Participants (Count of Participants) | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hemoglobin (hypo) | Prothrombin international normalized ratio increased | Lymphocytes (hypo) | Lymphocytes (hyper) | Neutrophils (hypo) | Platelets (hypo) | Leukocytes (hypo) | Albumin (hypo) | Alkaline phosphatase | Alanine aminotransferase | Aspartate aminotransferase | Bilirubin | Creatine (phospho)kinase | Corrected Calcium (hypo) | Corrected Calcium (hyper) | Creatinine | Gamma-glutamyl transferase | Glucose serum fasting (hypo) | Glucose serum fasting (hyper) | Magnesium (hypo) | Magnesium (hyper) | Phosphate (hypo) | Potassium (hypo) | Potassium (hyper) | Sodium (hypo) | |
Part 1: LGX818 300 mg | 11 | 1 | 15 | 11 | 5 | 1 | 3 | 5 | 3 | 8 | 4 | 0 | 1 | 1 | 0 | 15 | 29 | 4 | 12 | 1 | 0 | 25 | 1 | 4 | 1 |
Part 1: Vemurafenib 960 mg BID | 13 | 3 | 41 | 5 | 3 | 1 | 4 | 2 | 4 | 8 | 4 | 13 | 1 | 3 | 2 | 48 | 15 | 3 | 12 | 0 | 1 | 35 | 3 | 6 | 1 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 19 | 0 | 20 | 14 | 14 | 2 | 5 | 3 | 6 | 15 | 12 | 1 | 32 | 1 | 0 | 35 | 43 | 2 | 20 | 0 | 2 | 18 | 1 | 6 | 7 |
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
Intervention | Participants (Count of Participants) | |||||
---|---|---|---|---|---|---|
Rash | Skin infections | PPE syndrome | Photosensitivity | Nail disorders | Severe cutaneous adverse reactions | |
Part 1: LGX818 300 mg | 10 | 1 | 26 | 0 | 0 | 1 |
Part 1: Vemurafenib 960 mg BID | 25 | 0 | 2 | 3 | 0 | 5 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 2 | 4 | 0 | 1 | 0 | 0 |
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
Intervention | Participants (Count of Participants) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
QT: Increase >30 ms | QT: Increase >60 ms | QT: New >450 ms | QT: New >480 ms | QT: New >500 ms | QTcF: Increase >30 ms | QTcF: Increase >60 ms | QTcF: New >450 ms | QTcF: New >480 ms | QTcF: New >500 ms | QTcB: Increase >30 ms | QTcB: Increase >60 ms | QTcB: New >450 ms | QTcB: New >480 ms | QTcB: New >500 ms | Heart rate: New <60 bpm | Heart rate: New <100 bpm | |
Part 1: LGX818 300 mg | 68 | 19 | 15 | 4 | 2 | 56 | 7 | 39 | 7 | 5 | 74 | 15 | 76 | 23 | 10 | 37 | 23 |
Part 1: Vemurafenib 960 mg BID | 81 | 24 | 17 | 3 | 2 | 76 | 10 | 42 | 5 | 3 | 78 | 14 | 65 | 20 | 8 | 16 | 18 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 105 | 27 | 23 | 5 | 2 | 50 | 10 | 25 | 7 | 1 | 47 | 11 | 47 | 12 | 3 | 58 | 14 |
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
Intervention | Participants (Count of Participants) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Sitting Pulse Rate (bpm): High | Sitting Pulse Rate (bpm): Low | Sitting Systolic Blood Pressure (mmHg): High | Sitting Systolic Blood Pressure (mmHg): Low | Sitting Diastolic Blood Pressure (mmHg): High | Sitting Diastolic Blood Pressure (mmHg): Low | Weight (kg): High | Weight (kg): Low | Body temperature (degree C): High | Body temperature (degree C): Low | |
Part 1: LGX818 300 mg | 7 | 8 | 14 | 4 | 5 | 7 | 10 | 8 | 11 | 74 |
Part 1: Vemurafenib 960 mg BID | 8 | 2 | 31 | 1 | 13 | 5 | 8 | 13 | 17 | 57 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 1 | 3 | 27 | 7 | 23 | 9 | 44 | 2 | 19 | 76 |
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
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Retinopathy excluding RVO | RVO | Uveitis-type events | |
Part 1: LGX818 300 mg | 0 | 1 | 0 |
Part 1: Vemurafenib 960 mg BID | 0 | 0 | 0 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 5 | 0 | 1 |
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
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Grade 0 | Grade 2 | Grade 3 | Grade 4 | Missing | |
Part 1: LGX818 300 mg | 161 | 17 | 4 | 0 | 10 |
Part 1: LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 127 | 56 | 3 | 0 | 6 |
Part 1: Vemurafenib 960 mg BID | 161 | 16 | 2 | 0 | 7 |
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
Intervention | percentage of participants (Number) | |
---|---|---|
Participants with AEs | Participants with SAEs | |
Part 1: LGX818 300 mg | 99.5 | 34.9 |
Part 1: Vemurafenib 960 mg BID | 99.5 | 37.1 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 98.4 | 34.4 |
(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
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1: LGX818 300 mg | 58.1 | 1190 | 4090 | 1850 | 73.6 | 53.8 |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 18.6 | 1640 | 6860 | 3400 | 119 | 150 |
(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
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1:LGX818 450 mg QD+MEK162 45 mg BID (Combo 450) | 2.95 | 426 | 832 | 330 | 81.0 | 68.1 |
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 4.0 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)
Intervention | Participants (Count of Participants) | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hemoglobin (hypo) | Prothrombin international normalized ratio increased | Lymphocytes (hypo) | Lymphocytes (hyper) | Neutrophils (hypo) | Platelets (hypo) | Leukocytes (hypo) | Albumin (hypo) | Alkaline phosphatase (hyper) | Alanine aminotransferase | Aspartate aminotransferase | Bilirubin | Creatine kinase | Corrected Calcium (hypo) | Creatinine | Gamma-glutamyl transferase | Glucose 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 mg | 16 | 1 | 25 | 13 | 9 | 2 | 5 | 9 | 4 | 9 | 5 | 0 | 1 | 2 | 26 | 38 | 4 | 17 | 1 | 0 | 33 | 1 | 7 | 3 | 0 |
Part 2: LGX818 300 mg | 5 | 0 | 10 | 2 | 4 | 1 | 2 | 4 | 1 | 1 | 1 | 0 | 0 | 1 | 11 | 9 | 0 | 5 | 0 | 0 | 8 | 0 | 3 | 2 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 16 | 4 | 28 | 11 | 19 | 1 | 3 | 7 | 11 | 18 | 15 | 2 | 40 | 4 | 44 | 38 | 3 | 27 | 0 | 3 | 26 | 2 | 8 | 4 | 2 |
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)
Intervention | Participants (Count of Participants) | |||||
---|---|---|---|---|---|---|
Rash | Skin infection | PPE syndrome | Photosensitivity | Nail disorders | Severe cutaneous adverse reactions | |
Part 1 + Part 2: LGX818 300 mg | 13 | 1 | 30 | 0 | 0 | 1 |
Part 2: LGX818 300 mg | 3 | 0 | 4 | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 2 | 7 | 1 | 0 | 0 | 0 |
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)
Intervention | Participants (Count of Participants) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
QT (ms): Increase from baseline > 30 | QT (ms): Increase from baseline > 60 | QT (ms): New > 450 | QT (ms): New > 480 | QT (ms): New > 500 | QTcF (ms): Increase from baseline > 30 | QTcF (ms): Increase from baseline > 60 | QTcF (ms): New > 450 | QTcF (ms): New > 480 | QTcF (ms): New > 500 | QTcB (ms): New > 450 | QTcB (ms): New > 480 | QTcB (ms): New > 500 | QTcB (ms): Increase from baseline > 30 | QTcB (ms): Increase from baseline > 60 | Heart rate (bpm): New < 60 | Heart rate (bpm): New > 100 | |
Part 1 + Part 2: LGX818 300 mg | 95 | 25 | 20 | 6 | 2 | 76 | 14 | 50 | 12 | 6 | 104 | 29 | 11 | 98 | 23 | 42 | 33 |
Part 2: LGX818 300 mg | 27 | 6 | 5 | 2 | 0 | 20 | 7 | 11 | 5 | 1 | 28 | 6 | 1 | 24 | 8 | 5 | 10 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 132 | 34 | 34 | 9 | 4 | 59 | 13 | 36 | 11 | 2 | 70 | 23 | 10 | 69 | 22 | 82 | 8 |
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)
Intervention | Participants (Count of Participants) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Sitting Pulse Rate (bpm): High | Sitting Pulse Rate (bpm): Low | Sitting Systolic Blood Pressure (mmHg): High | Sitting Systolic Blood Pressure (mmHg): Low | Sitting Diastolic Blood Pressure (mmHg): High | Sitting Diastolic Blood Pressure (mmHg): Low | Weight (kg): High | Weight (kg): Low | Body temperature (°C): High | Body temperature (°C): Low | |
Part 1 + Part 2: LGX818 300 mg | 10 | 9 | 17 | 8 | 7 | 9 | 11 | 9 | 16 | 96 |
Part 2: LGX818 300 mg | 3 | 1 | 3 | 4 | 2 | 2 | 1 | 1 | 5 | 22 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 7 | 11 | 40 | 10 | 41 | 7 | 46 | 0 | 14 | 120 |
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)
Intervention | Participants (Count of Participants) | ||
---|---|---|---|
Retinopathy excluding RVO | RVO | Uveitis-type events | |
Part 1 + Part 2: LGX818 300 mg | 0 | 1 | 0 |
Part 2: LGX818 300 mg | 0 | 0 | 0 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 4 | 0 | 4 |
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)
Intervention | Participants (Count of Participants) | ||||
---|---|---|---|---|---|
Grade 0 | Grade 2 | Grade 3 | Grade 4 | Missing | |
Part 1 + Part 2: LGX818 300 mg | 235 | 22 | 4 | 0 | 15 |
Part 2: LGX818 300 mg | 74 | 5 | 0 | 0 | 5 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 181 | 71 | 3 | 0 | 2 |
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)
Intervention | percentage of Participants (Number) | |
---|---|---|
AEs | SAEs | |
Part 1 + Part 2: LGX818 300 mg | 98.6 | 33.3 |
Part 2: LGX818 300 mg | 96.4 | 29.8 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 98.1 | 29.2 |
(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
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 1 + Part 2: LGX818 300 mg | 39.7 | 1250 | 4170 | 1980 | 60.1 | 60.6 |
Part 2: LGX818 300 mg | 0.0145 | 1370 | 4310 | 2250 | 29.5 | 79.5 |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 5.02 | 1360 | 4390 | 2420 | 121 | 74.1 |
(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
Intervention | nanogram per milliliter (Mean) | |||||
---|---|---|---|---|---|---|
Cycle 1 Day 1: pre-dose | Cycle 1 Day 1: 0.5 hours post dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 4 to 8 hours post dose | Cycle 2 Day 1: pre-dose | Cycle 3 Day 1: pre-dose | |
Part 2: LGX818 300 mg QD+MEK162 45 mg BID (Combo 300) | 1.68 | 366 | 642 | 287 | 72.3 | 73.2 |
13 reviews available for carbamates and Melanoma
Article | Year |
---|---|
STARBOARD: encorafenib + binimetinib + pembrolizumab for first-line metastatic/unresectable
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Benzimidazoles; Carbamates; Humans; M | 2022 |
An evaluation of encorafenib for the treatment of melanoma.
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanoma; Mutati | 2020 |
An overview of binimetinib for the treatment of melanoma.
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.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Melanom | 2020 |
[Management of toxicities of BRAF inhibitors and MEK inhibitors in advanced melanoma].
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.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Azetidines; Benzimidazoles; C | 2017 |
Development of encorafenib for BRAF-mutated advanced melanoma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carbamates; Clinical Trials, Phase III as T | 2018 |
Encorafenib and Binimetinib: First Global Approvals.
Topics: Benzimidazoles; Carbamates; Drug Approval; Humans; MAP Kinase Kinase Kinases; Melanoma; Molecular St | 2018 |
[What's new in oncodermatology?]
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Ben | 2018 |
Encorafenib in combination with binimetinib for unresectable or metastatic melanoma with BRAF mutations.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Disease-Free Su | 2019 |
Encorafenib and binimetinib for the treatment of BRAF V600E/K-mutated melanoma.
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?
Topics: Benzamides; Benzimidazoles; Carbamates; Humans; Melanoma; Mutation; Piperidines; Protein Kinase Inhi | 2017 |
9 trials available for carbamates and Melanoma
Article | Year |
---|---|
Adverse events associated with encorafenib plus binimetinib in the COLUMBUS study: incidence, course and management.
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.
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
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).
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.
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.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Biom | 2018 |
CI-980 in advanced melanoma and hormone refractory prostate cancer.
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.
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).
Topics: Alkynes; Antineoplastic Agents; Bone Marrow; Carbamates; Clinical Trials as Topic; Cyclohexanes; Eva | 1970 |
52 other studies available for carbamates and Melanoma
Article | Year |
---|---|
Switch from dabrafenib/trametinib combination therapy to encorafenib/binimetinib combination therapy with transition of serum lactate dehydrogenase level in melanoma: A case report.
Topics: Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; Humans; Imidazoles; Lact | 2022 |
Conjunctival malignant melanoma treated successfully with BRAF inhibitor: encorafenib plus binimetinib.
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].
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.
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.
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.
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.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Brain Neoplasms; Carbamates; | 2020 |
Multiple Pigmented Lesions of the Breast Following Ipsilateral Breast Carcinoma.
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.
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.
Topics: Antineoplastic Combined Chemotherapy Protocols; Arthritis; Benzimidazoles; Carbamates; Humans; Melan | 2020 |
Preclinical discovery and clinical development of encorafenib for the treatment of melanoma.
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.
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.
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.
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.
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.
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.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Carbamates; C | 2021 |
[Long-term efficacy of encorafenib plus binimetinib combined treatment: case report.]
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.
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.
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.
Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Brain Neoplasms; Carbamates; F | 2021 |
Successful encorafenib desensitization in a patient with recurrent metastatic melanoma.
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.
Topics: Antineoplastic Agents; Benzimidazoles; Carbamates; Female; Glomerulonephritis; Humans; Kidney; Lung | 2017 |
In the pipeline: encorafenib and binimetinib in BRAF-mutated melanoma.
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.
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.
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.
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?
Topics: Benzimidazoles; Carbamates; Humans; Melanoma; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-r | 2018 |
Encorafenib - a new agent for advanced-stage disease.
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.
Topics: Aged, 80 and over; Benzimidazoles; Carbamates; Female; Humans; Melanoma; Protein Kinase Inhibitors; | 2018 |
Encorafenib plus binimetinib: an embarrassment of riches.
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.
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.
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.
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.
Topics: Benzimidazoles; Carbamates; Fibrosarcoma; Humans; Melanoma; Sulfonamides | 2019 |
Proteomic identification of a marker signature for MAPKi resistance in melanoma.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Topics: Animals; Antineoplastic Agents; Benzimidazoles; Carbamates; Ependymoma; Leukemia L1210; Leukemia, Ex | 1975 |
Initial clinical studies with copovithane.
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.
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.
Topics: Amines; Animals; Biphenyl Compounds; Carbamates; Dihydroxyphenylalanine; Endoplasmic Reticulum; Fuma | 1973 |
Effect of inhibitors on phenoloxidase of Mycobacterium leprae.
Topics: Antimetabolites; Basidiomycota; Carbamates; Catechol Oxidase; Dihydroxyphenylalanine; Enzyme Repress | 1969 |
The tyrosine hydroxylase activity of mammalian tyrosinase.
Topics: 5-Hydroxytryptophan; Animals; Ascorbic Acid; Carbamates; Cricetinae; Cyanides; Dihydroxyphenylalanin | 1966 |