602P - 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

Background

In the randomized, 2-part, multicenter, open-label, phase 3 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. Table: 602P

^aIncludes non-CR/non-PD. ^bIncludes best response of unknown or no assessment.

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.

Clinical trial identification

NCT01909453.

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.

Legal entity responsible for the study

The COLUMBUS study was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.

Funding

The COLUMBUS study was sponsored by Array BioPharma, which was acquired by Pfizer in July 2019.

Disclosure

A.M. Haydon: Financial Interests, Personal, Advisory Board: MSD, BMS, Novartis. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Personal, 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. C. Robert: Financial Interests, Personal, Other, Consultancy fees: BMS, Roche, PIERRE FABRE, Novartis, Sanofi, MSD, AstraZeneca, Pfizer, SUN Pharma. C. Garbe: Financial Interests, Personal, Advisory Board: CeCaVa, MSD, NeraCare, Philogen; Non-Financial Interests, Personal, Leadership Role, President: European Association of Dermatooncology (EADO). H. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Sanofi; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, Sanofi; Financial Interests, Institutional, Local PI: Amgen, MSD, BMS, REPLIMMUNE, IOVANCE, Bayer; Financial Interests, Personal, Steering Committee Member: Amgen, REPLIMMUNE; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Lilly, PIERRE FABRE. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Sun Pharma. 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 and travel support: Bio-AI Health; Financial Interests, Personal, Other, Consultant role: Medicenna; 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: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Institutional, Funding, Clinical Trial: Pfizer/Array, Roche Genentech, Sanofi; Financial Interests, Personal, Advisory Board: Erasca; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Non-Financial Interests, Personal, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Personal, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Personal, Member: SITC, ASCO, EORTC Melanoma Cooperative Group, SMR, AIOM; Non-Financial Interests, Personal, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Personal, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC). All other authors have declared no conflicts of interest.