1089P - Adjuvant nivolumab (NIVO) vs ipilimumab (IPI) in resected stage III/IV melanoma: 7-y results from CheckMate 238

Background

In the phase III CheckMate 238 trial, NIVO showed improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) vs IPI in pts with high-risk, resected stage IIIB–C or IV melanoma, sustained for 5 y; no significant difference was observed in OS. Updated 7-y results are presented.

Methods

Pts aged > 15 y (stratified by disease stage and PD-L1 status) were randomized 1:1 to NIVO 3 mg/kg Q2W (n = 453) or IPI 10 mg/kg Q3W for 4 doses then Q12W (n = 453), for up to 1 y or until disease recurrence/unacceptable toxicity. Endpoints included RFS, OS, DMFS in stage III pts, and safety. Progression-free survival through next-line therapy (PFS2) and melanoma-specific survival (MSS) are post hoc analyses presented here for the first time.

Results

At 7-y, RFS remained superior with NIVO vs IPI (HR 0.74; 95% CI 0.62–0.88) with DMFS and PFS2 also favoring NIVO (Table). New recurrence events since 5 y included 12 new events (2 regional, 7 distant, 2 new primary, 1 death) for NIVO and 7 new events (1 local, 2 distant, 4 deaths) for IPI; 6% and 5% of at-risk pts relapsed after yr 5. For NIVO vs IPI respectively, there were a total of 13 and 12 new deaths overall (8 and 10 due to melanoma). Subsequent systemic therapy was less frequent with NIVO than IPI (36% vs 44%), including subsequent immunotherapy in 26% vs 36% of pts. No new voluntarily reported late-emergent treatment-related adverse events were reported since the 4-y database lock, and overall rates remain low.

Conclusions

At 7-y follow-up, the longest follow-up of any anti–PD-1 therapy in this setting, NIVO showed superior long-term RFS vs IPI in pts with stage IIIB–C or IV resected melanoma. DMFS and PFS2 also favored NIVO, and OS and MSS rates were high in both arms, with no significant difference between arms. The additional recurrences at 7-y vs 5-y follow-up may indicate a clinical consideration for imaging and follow-up visits beyond 5 y. Table: 1089P

^aNIVO vs IPI (Stratified Cox proportional hazards model). ^bIn stage III patients (NIVO = 307; IPI = 366).

Clinical trial identification

NCT02388906.

Editorial acknowledgement

Professional medical writing and editorial assistance were provided by Jessica Augello, PhD, and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Supported by Bristol Myers Squibb Company and ONO Pharmaceutical.

Disclosure

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, 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, 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, SMR, AIOM. M. Del Vecchio: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Immunocore. 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, Steering Committee Member: Amgen, Replimune; Financial Interests, Institutional, Local PI: Amgen, MSD, BMS, Replimune, Iovance, Bayer; Financial Interests, Institutional, Research Grant: BMS, Pfizer, Lilly, Pierre Fabre. 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. S. Dalle: Financial Interests, Institutional, Research Grant: BMS, MSD, Pierre Fabre; Financial Interests, Personal, Financially compensated role: BMS, MSD, Pierre Fabre; Financial Interests, Personal, Stocks/Shares: Sanofi. C.L. Cowey: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, EMD Serono, Eisai, Regeneron, Iovance. M. Schenker: Financial Interests, Institutional, Research Grant: BMS, AbbVie, Amgen, Astellas, AstraZeneca, Bayer, BeiGene, Clovis, Eli Lilly, Gilead, GSK, Merck, MSD, Mylan, Novartis, Pfizer, PharmaMar, Regeneron, Roche, Samsung Pharmaceuticals, Serono, Tesaro. J.J. Grob: Financial Interests, Personal, Advisory Board: BMS, MSD, Pierre Fabre, Sanofi, Novartis, Philogen. V. Chiarion Sileni: Financial Interests, Personal, Advisory Board, analysis of treatment modality (diagnosis, stanging, surgery, radiotherapy, systemic therapy for Merkel cell carcinoma in Italy: Merck-Serono; Financial Interests, Institutional, Invited Speaker, treatment option for BRAF mutated melanoma: Novartis; Financial Interests, Institutional, Invited Speaker, Treatment choices for BRAF mutated melanoma, evidence-based, and biologically supported: Pierre Fabre; Financial Interests, Institutional, Invited Speaker, Immunotherapy for melanoma treatment present and future: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, registration, and accommodation to attend ASCO annual meetings: Pierre Fabre. I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Roche, GSK, AstraZeneca, Celgene, Regeneron, Sanofi, Merck Serono, Highlight Therapeutics, Bioline Rx, Sun Pharma, Immunocore; Financial Interests, Personal and Institutional, Coordinating PI, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Coordinating PI, GEM1801 clinical study: Novartis, BMS, Roche, Pierre Fabre, Incyte, MSD; Financial Interests, Institutional, Coordinating PI, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Member of Board of Directors: Spanish Melanoma Group. M.O. Butler: Financial Interests, Personal, Speaker’s Bureau: BMS, Merck, Novartis, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board: Merck, BMS, Novartis, Adaptimmune, Instil Bio, Iovance, Sun Pharma, GSK, Sanofi, LaRoche Possey, Pfizer, Medison, IDEAYA, Regeneron; Financial Interests, Personal, Research Grant: Merck, Takara Bio, Novartis. A.M. Di Giacomo: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: Sanofi. M. Pe Benito, M. Askelson: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. J.S. Weber: Financial Interests, Personal, Advisory Board, Ad Boards: BMS; Financial Interests, Personal, Advisory Board: Merck, GSK, Incyte, Genentech, Pfizer, Biond, OncoC4, AstraZeneca, Regeneron, ImCheck, Novartis; Financial Interests, Personal, Stocks/Shares: Biond, Evaxion, Instil Bio, OncoC4; Financial Interests, Personal, Royalties: Moffitt Cancer Center; Financial Interests, Institutional, Local PI: BMS, Regeneron; Financial Interests, Institutional, Coordinating PI: Merck, Novartis; Non-Financial Interests, Principal Investigator: Moderna, BMS; Non-Financial Interests, Member: ASCO. J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debiopharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. All other authors have declared no conflicts of interest.