1041MO - 5-year update on COLUMBUS: A randomized phase III trial of encorafenib (enco) + binimetinib (bini) versus enco or vemurafenib (vem) in patients (pts) with BRAF V600-mutant melanoma

Background

Combined BRAF/MEK inhibitor therapy has demonstrated benefits on progression-free survival (PFS) and overall survival (OS) and is standard of care for the treatment (tx) of advanced BRAF V600-mutant (BRAF ^V600) melanoma. Here we report additional data from the 5-year update of the ongoing COLUMBUS trial.

Methods

In COLUMBUS Part 1, 577 pts with advanced/metastatic BRAF ^V600 melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to enco 450 mg once daily + bini 45 mg twice daily, enco 300 mg once daily, or vem 960 mg twice daily. An updated analysis was conducted after 65 months’ minimum follow-up. Data are as is.

Results

In the enco + bini arm, the 5-year OS rate (95% CI) in all pts (n=192), those with lactate dehydrogenase (LDH) ≤ upper limit of normal (ULN) at baseline (n=137), and low tumor burden (n=88) was 35% (28–42), 45% (36–53), and 48% (37–58), respectively (data cut-off: Sep 15, 2020). Other efficacy results are shown in the table. Safety results were consistent with the known tolerability profile of enco + bini. Adverse events (AEs) occurring in ≥ 20% of enco + bini pts were nausea, diarrhea, vomiting, arthralgia, fatigue, increased blood creatinine phosphokinase (CPK), headaches, constipation, asthenia, and pyrexia. Grade 3/4 AEs occurring in ≥ 2.5% of pts in the enco + bini were hypertension, pyrexia, abdominal pain, diarrhea, and vomiting. Grade 3/4 abnormal laboratory values occurring in ≥ 2.5% pts in the enco + bini arm were increased gamma-glutamyl transferase, increased blood CPK, anemia, increased alanine transaminase, and hyperglycemia. 12%–14% of pts in each arm discontinued tx due to AEs. The most common anti-cancer tx after enco + bini were checkpoint inhibitors. Additional analyses will be presented. Table: 1041MO

*% (95% CI) ^†n (%)

Conclusions

Updated results with enco + bini indicate continued long-term benefit in pts with advanced/metastatic BRAF ^V600 melanoma.

Clinical trial identification

NCT01909453; release date: July 26, 2013.

Editorial acknowledgement

Editorial and medical writing support was provided by Raya Mahbuba at Caudex and was funded by Pfizer.

Legal entity responsible for the study

Pfizer.

Funding

Array BioPharma, which was acquired by Pfizer in July 2019.

Disclosure

R. Dummer: Financial Interests, Personal, Advisory Board: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, touchIME. K.T. Flaherty: Financial Interests, Personal, Member of the Board of Directors: Clovis Oncology, Strata Oncology, Vivid Biosciences, Checkmate Pharmaceuticals; Financial Interests, Personal, Advisory Board: X4 Pharmaceuticals, PIC Therapeutics, Sanofi, Amgen, Asana, Adaptimmune, Fount, Aeglea, Shattuck Labs, Tolero, Apricity, Oncoceutics, Fog Pharma, Neon, Tvardi, xCures, Monopteros, Vibliome; Financial Interests, Personal, Other: Lilly, Novartis, Genentech, BMS, Merck, Takeda, Verastem, Boston Biomedical, Pierre Fabre, Debiopharm; Financial Interests, Personal and Institutional, Funding: Novartis, Sanofi. C. Robert: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca. A. Arance: Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Funding: Pierre Fabre; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Funding: Novartis; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Funding: Roche; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Funding: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Funding: MSD; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Merck; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Funding: Merck; Financial Interests, Personal, Other, Consultant, Travel, Accommodations, Expenses: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Funding: Sanofi; Financial Interests, Personal, Funding: Amgen. J.W.B. de Groot: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Servier. C. Garbe: Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal and Institutional, Advisory Board: Neracare; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Advisory Board: Sanofi. H.J. Gogas: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Non-Financial Interests, Personal, Member, Steering committee: Amgen; Financial Interests, Institutional, Other, Local PI: Amgen; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Local PI: Bristol Myers Squibb; Financial Interests, Institutional, Other, Local PI: MSD; Financial Interests, Institutional, Research Grant: Pfizer. R. Gutzmer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall Hermal, SUN, Sanofi, Pierre-Fabre; Financial Interests, Institutional, Other, Clinical study fees: Roche, BMS, MSD, Novartis, Amgen, Merck Serono, SUN, Sanofi, Pierre-Fabre, Philogen, Pfizer; Financial Interests, Personal, Advisory Board: BMS, Roche, Novartis, Almirall Hermal, MSD, Amgen, SUN, Sanofi, Pierre-Fabre, 4SC, Bayer, MerckSerono, Pfizer; Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Johnson & Johnson, Amgen, Merck-Serono, SUN Pharma, Sanofi; Non-Financial Interests, Personal, Other, Travel/meeting support: Roche, BMS, SUN, Merck-Serono, Pierre-Fabre. G. Liszkay: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Principal Investigator: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Principal Investigator: Pfizer; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Principal Investigator: Incyte Corporation. C. Loquai: Financial Interests, Personal, Advisory Board: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma, Biontech, Almiral Hermal; Financial Interests, Personal, Speaker’s Bureau: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma; Financial Interests, Personal, Other, Travel reimbursement: MSD, BMS, Merck, Novartis, Roche, Pierre Fabre, Sanofi, Sun Pharma, Biontech, Almiral Hermal, Kyowa Kirin . M. Mandala: Financial Interests, Institutional, Advisory Board: Novartis; Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Institutional, Advisory Board: Pierre Fabre; Financial Interests, Institutional, Invited Speaker: Pierre Fabre; Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Advisory Board: Sanofi; Financial Interests, Institutional, Invited Speaker: Sanofi. D. Schadendorf: Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: NEKTAR; Financial Interests, Personal, Advisory Board: Neracare; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi/Regeneron; Financial Interests, Personal, Member, Steering Committee Member: 4SC; Financial Interests, Institutional, Principal Investigator, Coordinating PI: 4SC; Financial Interests, Institutional, Research Grant: Array/Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Member, Steering Committee Member: Bristol Myers Squibb; Financial Interests, Personal, Member, Steering Committee Member: MSD; Financial Interests, Institutional, Principal Investigator, Coordinating PI: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Member, Steering Committee Member: Nektar; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Nektar; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Member, Steering Committee Member: Novartis; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Philogen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pierre Fabre; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Sanofi; Non-Financial Interests, Personal, Member, Board of Directors: EORTC-MG. N. Yamazaki: Financial Interests, Personal and Institutional, Speaker’s Bureau: Ono; Financial Interests, Personal and Institutional, Research Grant: Ono. F. Zohren: Financial Interests, Personal, Full or part-time Employment: Pfizer. M. Edwards: Financial Interests, Institutional, Full or part-time Employment, Salary paid by Pfizer: Pfizer. P.A. Ascierto: Financial Interests, Personal and Institutional, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: Roche-Genentech; Financial Interests, Personal and Institutional, Research Grant: Roche-Genentech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Array; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Medimmune; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Syndax; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal and Institutional, Advisory Board: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: Ultimovacs; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Italfarmaco; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: Nouscom; Non-Financial Interests, Institutional, Principal Investigator: Takis; Financial Interests, Personal, Advisory Board: Lunaphore; Financial Interests, Personal, Advisory Board: Seagen. All other authors have declared no conflicts of interest.