Found 1 Presentation For Request "1113p"
1113P - COLUMBUS 7-year update: A randomized, open-label, phase III trial of encorafenib (enco) + binimetinib (bini) vs vemurafenib (vemu) or enco in patients (pts) with BRAF V600–mutant melanoma
- Dirk Schadendorf (Essen, Germany)
Abstract
Background
In the randomized, 2-part, multicenter, open-label, phase III COLUMBUS study, enco + bini (approved in the US, EU, and other countries) and enco alone improved PFS and OS rates vs vemu in patients with BRAF V600–mutant metastatic melanoma. Here we report data from the 7-year analysis of COLUMBUS part 1.
Methods
Pts with advanced or metastatic BRAF V600–mutant melanoma were randomized 1:1:1 to enco 450 mg QD + bini 45 mg BID, vemu 960 mg BID, or enco 300 mg QD. Pts were treatment (tx)-naive or had progression after 1L immunotherapy. No prior BRAF/MEKi was allowed. Randomization was stratified by cancer stage (IIIB + IIIC + IVM1a + IVM1b vs IVM1c), ECOG PS (0 vs 1), and prior 1L immunotherapy (yes vs no).
Results
577 pts were randomized to enco + bini (n=192), vemu (n=191), or enco alone (n=194). Updated analyses were conducted after >93 mo of minimum follow-up (cutoff: Jan 13, 2023). The 7-year PFS and OS rates (95% CI) were 21.2% (14.7, 28.4) and 27.4% (21.2, 33.9) in the enco + bini arm and 6.4% (2.1, 14.0) and 18.2% (12.8, 24.3) in the vemu arm, respectively. TEAEs (≥30% with enco + bini) were nausea, diarrhea, vomiting, arthralgia, and fatigue. Grade 3/4 TEAEs (≥5% with enco + bini) were γ-glutamyltransferase increased, blood CPK increased, hypertension, ALT increased, and anemia. Across arms, 16% to 20% of pts discontinued tx due to AEs. After tx discontinuation, 15% of pts from the enco + bini arm, 42% from the vemu arm, and 28% from the enco alone arm received BRAF/MEKi tx; 42% from the enco + bini arm, 49% from the vemu arm, and 43% from the enco alone arm received checkpoint inhibitors.
Conclusions
With a median duration of follow-up of 100 mo, the 7-year analysis from COLUMBUS part 1 confirms the long-term, sustained efficacy and known safety profile of enco + bini, with no new safety signals emerging, in pts with BRAF V600–mutant metastatic melanoma. aIncludes non-CR/non-PD. bIncludes best response of unknown or no assessment.
By BICR Enco + bini (n=192) Vemu (n=191) Enco alone (n=194) 14.9 (11.0, 20.2) 7.3 (5.6, 7.9) 9.6 (7.4, 14.8) 33.6 (24.4, 39.2) 16.9 (14.0, 24.5) 23.5 (19.6, 33.6) 21.2 (14.7, 28.4) 6.4 (2.1, 14.0) 15.8 (9.3, 23.8) 27.4 (21.2, 33.9) 18.2 (12.8, 24.3) 31.7 (24.9, 38.7) 29 (15.1) 16 (8.4) 17 (8.8) 94 (49.0) 62 (32.5) 83 (42.8) 54 (28.1) 77 (40.3) 63 (32.5) 15 (7.8) 36 (18.9) 31 (16.0) 64.1 (56.8, 70.8) 40.8 (33.8, 48.2) 51.5 (44.3, 58.8) 92.2 (87.4, 95.6) 81.2 (74.9, 86.4) 84.0 (78.1, 88.9)
Clinical trial identification
NCT01909453 CMEK162B2301 C4221004 (Other Identifier: Alias Study Number) 2013-001176-38 (EudraCT Number) Last Update Posted: April 24, 2023.
Editorial acknowledgement
The authors would like to thank Joe Kleha of Pfizer for his contribution to the data analysis and interpretation. Medical writing support was provided by Asu Erden, PhD, of Health Interactions, Nucleus Global, and was funded by Pfizer.
Legal entity responsible for the study
The COLUMBUS study was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.
Funding
Pfizer, Inc.
Disclosure
D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Novartis, BMS, MSD; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Philogen; Financial Interests, Institutional, Research Grant: BMS, MSD; Non-Financial Interests, Member of Board of Directors: EORTC-MG. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, CatalYm, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer, Simcere. K.T. Flaherty: Financial Interests, Personal, Other, Consultant: Takeda, Transcode Therapeutics, Novartis; Financial Interests, Personal, Member of Board of Directors: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics; Financial Interests, Personal, Stocks/Shares: Clovis Oncology, Strata Oncology, Checkmate Pharmaceuticals, Kinnate BioPharma, Scorpion Therapeutics, PIC Therapeutics, Apricity, Tvardi, xCures, Monopteros, Vibliome, ALX Oncology, Fog Pharma, Soley Therapeutics; Financial Interests, Personal, Ownership Interest: Nextech; Financial Interests, Institutional, Invited Speaker: Novartis, Pfizer. C. Robert: Financial Interests, Personal, Other, Consultancy fees: BMS, Roche, Pierre Fabre, Novartis, Sanofi, MSD, AstraZeneca, Pfizer. A.M. Arance Fernandez: Financial Interests, Personal, Advisory Board, Consultant /Advisory/Speaker/Travel, Accommodation, Expenses/: Pierre Fabre, Novartis, Roche, BMS, MSD, Merck, Sanofi; Financial Interests, Institutional, Other, Research Funding: Pierre Fabre, Novartis, MSD, BMS, Merck, Roche, Sanofi, Amgen. J.W. de Groot: Other, Institutional, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre, Servier. C. Garbe: Other, Institutional, Advisory Board: Amgen, Bristol Myers Squibb, MSD, NeraCare, Novartis, Pfizer, Philogen, Pierre Fabre, Roche, Sanofi. H. Gogas: Other, Institutional, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre; Other, Institutional, Other, Steering Committee Member: Amgen; Financial Interests, Institutional, Principal Investigator: Amgen, Bristol Myers Squibb, MSD; Financial Interests, Institutional, Other, Research Support: Bristol Myers Squibb, Pfizer. R. Gutzmer: Other, Institutional, Invited Speaker: Almirall, Amgen, Bristol Myers Squibb, Merck Serono, MSD, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharma; Other, Institutional, Other, Clinical Study Fees: Amgen, Bristol Myers Squibb, Merck, Serono, MSD, Novartis, Pfizer, Philogen, Pierre Fabre, Roche, Sanofi, Sun Pharma; Other, Institutional, Advisory Board: 4SC, Almirall, Amgen, Bayer, Bristol Myers Squibb, Merck Serono, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Sun Pharma; Other, Institutional, Other, Research Support: Amgen, Johnson & Johnson, Merck Serono, Novartis, Pfizer, Sanofi, Sun Pharma; Other, Institutional, Other, Travel/Meeting Support: Bristol Myers Squibb, Merck Serono, Pierre Fabre, Roche, Sun Pharma. G. Liszkay: Other, Institutional, Invited Speaker: Bristol Myers Squibb, MSD, Novartis, Pfizer, Roche; Other, Institutional, Principal Investigator: Bristol Myers Squibb, MSD, Novartis, Pfizer, Roche, Incyte; Other, Institutional, Advisory Board: Bristol Myers Squibb, MSD, Novartis, Pfizer, Roche. C. Loquai: Other, Institutional, Advisory Board: Almirall, BioNTech, Bristol Myers Squibb, Merck, MSD, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharma; Other, Institutional, Speaker’s Bureau: Bristol Myers Squibb, Merck, MSD, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharma; Other, Institutional, Other: Almirall, BioNTech, Bristol Myers Squibb, Kyowa Kirin, Merck, MSD, Novartis, Pierre Fabre, Roche, Sanofi, Sun Pharma. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. N. Yamazaki: Financial Interests, Personal, Invited Speaker, Advisory Board: Ono Pharmaceutical, MSD; Financial Interests, Personal, Advisory Board: Chugai Pharma; Financial Interests, Personal, Invited Speaker: Novartis, Bristol Myers Squibb Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, Bristol Myers Squibb Japan, Novartis, Astellas Amgen Biopharma, Merck Serono, Takara Bio. C.A. Guenzel, A. Polli, M. Thakur, A. di Pietro: Other, Institutional, Full or part-time Employment: Pfizer, Inc. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant and Advisory Role, Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: iTeos; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role. Travel support: Replimune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Advisory Board: Erasca; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. All other authors have declared no conflicts of interest.