1103P - Nivolumab (NIVO) plus relatlimab (RELA) vs NIVO in previously untreated metastatic or unresectable melanoma: 2-year subgroup analyses from RELATIVITY-047

Background

In RELATIVITY-047 (NCT03470922), NIVO + RELA previously demonstrated a statistically significant improvement in the primary endpoint of PFS per BICR vs NIVO, with a clinically meaningful (non-significant) statistical improvement in OS and a numerically higher ORR (secondary endpoints) in pts with previously untreated metastatic or unresectable melanoma. Post hoc analyses exploring the efficacy of NIVO + RELA vs NIVO according to baseline (BL) sites of metastasis (mets) and the time to development of CNS mets are reported herein.

Methods

Pts were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg fixed-dose combination (FDC) or NIVO 480 mg intravenously Q4W. Exploratory post hoc analyses were performed for PFS, OS, ORR, and melanoma-specific survival (MSS) by the no. of mets sites and the presence or absence of liver and lung mets. Time to development of new CNS mets per BICR was also assessed in both arms. Follow-up (f/u) brain imaging was not mandated per protocol.

Results

Median f/u was 25.3 mo; 581/714 pts were included in the BL mets analysis (mucosal and acral pts were excluded). Efficacy favored NIVO + RELA over NIVO in the majority of subgroups analyzed (Table). In pts without CNS mets at BL (348 in each arm), 17 pts (5%) in the NIVO + RELA arm and 31 pts (9%) in the NIVO arm developed new CNS mets per BICR over the course of tumor assessment f/u. Median time to the development of new CNS mets per BICR was 11.1 mo (range, 2.0–31.5) with NIVO + RELA and 6.6 mo (range, 0.6–32.7) with NIVO.

Conclusions

Efficacy outcomes generally favored NIVO + RELA over NIVO in pts with BL liver or lung mets and regardless of no. of BL sites of disease. Fewer pts on NIVO + RELA vs NIVO developed new CNS mets (and took a longer time to develop them), suggesting CNS activity with the FDC; however, incidence was low. Activity of NIVO + RELA in pts with CNS mets needs to be confirmed in a dedicated CNS study. Additional analyses will be presented. Table: 1103P

Unstratified HR; NIVO + RELA vs NIVO.

Clinical trial identification

NCT03470922.

Editorial acknowledgement

Jessica R. Augello, PhD, Ashfield MedComms.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Bristol Myers Squibb.

Disclosure

G.V. Long: Financial Interests, Personal, Speaker, Consultant, Advisor: Agenus Inc., Amgen Inc., Array Biopharma, Boehringer Ingelheim International GmbH, BMS, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L, Innovent Biologics USA Inc., Merck Sharp & Dohme (Australia) Pty Limited, Novartis Pharma AG; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: Agenus Inc., Amgen Inc., Array Biopharma, Boehringer Ingelheim International GmbH, BMS, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Highlight Therapeutics S.L, Innovent Biologics USA Inc., Merck Sharp & Dohme (Australia) Pty Limited, Novartis Pharma AG. F.S. Hodi: Financial Interests, Institutional, Research Grant: BMS, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Merck, Novartis, Genentech/Roche, CatalYm, Immunocore, Kairos, Zumutor, Corner Therapeutics, Curis, AstraZeneca; Financial Interests, Personal, Advisory Board: BioEntre, Iovance, Gossamer, Rheos, Surface, Compass Therapeutics, Apricity, Bicara, Checkpoint Therapeutics. E.J. Lipson: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Sanofi, Regeneron, Genentech, Eisai, Instil Bio, Natera, Nektar Therapeutics, Pfizer, Rain Therapeutics, CareDx, Immunocore, Novartis, Replimune, HUYA Bioscience International; Financial Interests, Personal, Other, Consultant: OncoSec; Financial Interests, Institutional, Coordinating PI: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Regeneron, Merck, Sanofi. 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, Member of Board of Directors: EORTC-MG. 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. M. Maio: Financial Interests, Personal, Advisory Board: BMS, Roche, GSK, Sanofi, Alfasigma, Amgen, SciClone, Eli Lilly, MSD, Incyte, Pierre Fabre, AstraZeneca; Financial Interests, Personal, Stocks/Shares: EpiGen, Theravance. M. Hernberg: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, MSD, Novartis, Med Engine; Financial Interests, Personal, Invited Speaker: Novartis, MSD, BMS. S. Prey: Financial Interests, Institutional, Advisory Board: BMS, MSD, Novartis. V.G. Atkinson: Financial Interests, Personal, Advisory Board: BMS, MSD, Nektar, Novartis, Pierre Fabre, QBiotics; Financial Interests, Personal, Invited Speaker: BMS, MSD, Novartis, Pierre Fabre, Limbic; Financial Interests, Personal, Other, Travel Support: BMS. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, Sanofi, MSD, Sun Pharma, Amgen, GSK, Pierre Fabre, Immunocore; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Sun Pharma, GSK, Onkowissen; Financial Interests, Institutional, Advisory Board: Novartis, BMS, Immunocore, Philogen, Sanofi; Financial Interests, Institutional, Research Grant: BMS, Sun Pharma; Financial Interests, Institutional, Local PI: Philogen, Genentech, 4SC, BioNTech, Idera, Iovance, Nektar, Pierre Fabre, Regeneron, Sanofi, Replimune; Financial Interests, Institutional, Coordinating PI: BMS, Immunocore, Novartis, Genmab; Financial Interests, Personal, Steering Committee Member: Immunocore, IO Biotech; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. G. Cinat: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Novartis, Merck Sharp & Dohme (MSD); Financial Interests, Personal, Expert Testimony: Bristol Myers Squibb, Novartis, Merck Sharp & Dohme (MSD); Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Novartis, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Personal, Other, Concensus Conference: Americas Health Foundation; Financial Interests, Personal, Full or part-time Employment: Angel H. Roffo Oncology Institute, University of Buenos Aires; Financial Interests, Personal, Local PI: Bristol Myers Squibb (BMS), Novartis, Merck Sharp & Dohme (MSD), Pfizer; Non-Financial Interests, Personal, Member: ASCO, Argentina Association of Clinical Oncology (Asociación Argentina de Oncología Clínica - AAOC). B. Ratto, S. Rodriguez, S. Dolfi: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. P.T. Wang: Financial Interests, Personal, Full or part-time Employment, Biostatistician employed full-time: BMS (Bristol Myers Squibb); Financial Interests, Personal, Stocks/Shares: BMS (Bristol Myers Squibb). H.A. Tawbi: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck, Novartis, Genentech, Eisai, Karyopharm, Iovance, Pfizer, Jazz Pharmaceuticals; Financial Interests, Institutional, Trial Chair: Bristol Myers Squibb; Financial Interests, Institutional, Local PI: Merck, RAPT Pharmaceuticals; Financial Interests, Institutional, Steering Committee Member: Novartis, Genentech; Financial Interests, Institutional, Funding: GSK, Eisai. All other authors have declared no conflicts of interest.