Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update
- PMID: 40513285
- DOI: 10.1016/j.ejca.2025.115547
Nivolumab plus relatlimab in advanced melanoma: RELATIVITY-047 4-year update
Abstract
Background: In phase 2/3 randomized RELATIVITY-047, nivolumab plus relatlimab demonstrated a statistically significant improvement in progression-free survival (PFS), a clinically meaningful but not statistically significant improvement in overall survival (OS), and a numerically higher objective response rate (ORR) versus nivolumab alone in patients with previously untreated advanced melanoma.
Methods: Descriptive 4-year updated analyses in patients treated with nivolumab 480 mg plus relatlimab 160 mg fixed-dose combination versus nivolumab 480 mg intravenously every 4 weeks are presented. Primary endpoint was PFS by blinded independent central review (BICR). Other endpoints included melanoma-specific survival (MSS).
Results: At 45.3 months' minimum follow-up, nivolumab plus relatlimab versus nivolumab PFS improvement was maintained: 4-year PFS rates were 30.6 % (95 % CI, 25.4-35.9) versus 23.6 % (95 % CI, 18.9-28.5); OS was numerically better with 4-year OS rates of 52.0 % (95 % CI, 46.6-57.1) versus 42.8 % (95 % CI, 37.5-47.9); and ORR difference was maintained at 43.9 % (95 % CI, 38.7-49.3) versus 33.4 % (95 % CI, 28.6-38.6), respectively. 4-year MSS rates were 59.7 % (95 % CI, 54.1-64.8) for nivolumab plus relatlimab and 49.6 % (95 % CI, 44.0-54.9) for nivolumab. Efficacy across the majority of prespecified subgroups favored the combination. No new or unexpected safety signals were identified.
Conclusions: With 4 years of follow-up, nivolumab plus relatlimab demonstrated durable improvement in outcomes versus nivolumab monotherapy for patients with previously untreated advanced melanoma. The durable benefit observed comes at a lower toxicity cost compared with other immuno-oncology combinations.
Trial registration: ClinicalTrials.gov Identifier: NCT03470922.
Keywords: Advanced melanoma; Immunotherapy; Long-term survival; Nivolumab; Relatlimab.
Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest EJL received institutional grants from Bristol Myers Squibb, Haystack, Merck, Regeneron, and Sanofi; received consulting fees or honoraria from Bristol Myers Squibb, HUYA Bioscience International, Immunocore, Merck KGaA, Novartis, and OncoSec; participated on a safety monitoring or advisory board for Bristol Myers Squibb, CareDx, Eisai, Genentech, Instil Bio, IO Biotech, Merck, Natera, Nektar, Pfizer, Rain Therapeutics, Regeneron, Replimune, Sanofi-Aventis, Sun Pharma, and Syneos Health; and has stock options with Iovance. FSH received research funding from Bristol Myers Squibb, Dynacure, Genentech, Merck, Novartis, and Pfizer; received consulting fees from Apricity, AstraZeneca, Bayer, Bicara, Bristol Myers Squibb, Catalym, Checkpoint Therapeutics, Compass Therapeutics, Corner Therapeutics, Curis, Gossamer, Immunocore, Iovance, Kairos, Merck, Nioentre, Novartis, Pliant, Puretech, Rheos, Solu Therapuetics, Vir Biotechnology, and Zumutor; received meeting or travel support from Parker Institute for Cancer Immunotherapy; received equipment, materials, drugs, medical writing support, gifts, or other services from Bristol Myers Squibb, Dynacure, Genetech, Merck, and Pfizer; and has patents planned, issued, or pending of Methods for Treating MICA-Related Disorders (#20100111973), Angiopoiten-2 Biomarkers Predictive including Anti-immune checkpoint response (#20170248603), Therapeutic peptides (#20160046716), Vaccine compositions and methods for restoring NKG2D pathway function against cancers, Patent number: 10279021, Tumor antigens and uses thereof (#7250291), ANTI-GALECTIN ANTIBODY BIOMARKERS PREDICTIVE OF ANTI-IMMUNE CHECKPOINT AND ANTI-ANGIOGENESIS RESPONSES, Compositions and Methods for Identification, Assessment, Prevention, and Treatment of Melanoma using PD-L1 Isoforms (#20160340407), METHODS OF USING PEMBROLIZUMAB AND TREBANANIB, Antibodies that bind to MHC class I polypeptide-related sequence A, Patent number 10106611, and Antibodies against EDIL3 and methods of use thereof. HAT received institutional grants from Bristol Myers Squibb, Dragonfly Therapeutics, Genetech/Roche, GlaxoSmithKline, Merck, Novartis, RAPT Therapeutics, and Regeneron; and performed a consulting or advisory role for Boxer Capital, Bristol Myers Squibb, Genetech/Roche, Jazz Pharmaceuticals, IO Biotech, Iovance Biotherapeutics, Medicenna, Merck, Novartis, Pfizer, and Regeneron. DS received research funding from Agenus, Amgen, Array BioPharma/Pfizer, Bristol Myers Squibb, Merck Sharp & Dohme Oncology, Novartis, Regeneron, and Roche; received honoraria from 4SC, Agenus, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo Japan, Erasca Inc, Immatics, Immunocore, InflarxGmbH, LabCorp, Merck Serono, Merck Sharp & Dohme, NeraCare GmbH, Novartis, Novigenix, Pamgene, Pfizer, Philogen, Pierre Fabre, Regeneron, Replimune, Roche/Genentech, Sanofi/Regeneron, Seagen, Sun Pharma, and Ultimovacs; received meeting or travel support from Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche/Genentech, and Sanofi/Regeneron; performed a consulting or advisory role for Roche/Genentech, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Sanofi/Regeneron, Agenus, AstraZeneca, Daiichi Sankyo, Erasca Inc, Immatics, Immunocore, NeraCare GmbH, Replimune; and was a member of a speakers Bureau for Bristol Myers Squibb, Merck KGaA, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sanofi/Regeneron PAA received institutional grants from Bristol Myers Squibb, Pfizer, Roche-Genentech, and Sanofi; received consulting fees from Bayer, Bio-Al Health, BionTech, Bristol Myers Squibb, Incyte, Italfarmaco, Lunaphore, Medicenna, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Philogen, Pierre Fabre, Replimmune, Roche-Genentech, Sandoz, Sanofi, Sun Pharma, and ValoTx; received meeting or travel support from Bio-Al Health, Merck Sharp & Dohme, Pfizer, Philogen, Pierre Fabre, and Replimmune; and participated on a safety monitoring or advisory board for Anaveon, Boehringer Ingelheim, Bristol Myers Squibb, Erasca, Genentech, Genmab, Menarini, Merck Sharp & Dohme, Nouscom, Novartis, Regeneron, and Roche. LM and ECG report no disclosures. PR received institutional funding from Bristol Myers Squibb, Novartis, Pfizer, and Roche; consulting fees from Bristol Myers Squibb, Genesis, Medison Pharma, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Philogen; honoraria from AstraZeneca, Bristol Myers Squibb, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, and Sanofi; and meeting or travel support from Pierre Fabre. HJG received honoraria from Bristol Myers Squibb, Genesis Pharmaceuticals, Merck Sharp & Dohme, Pierre Fabre, and Sanofi/Regeneron; received institutional funding support from Amgen, Bristol Myers Squibb, Iovance Biotherapeutics, Merck Sharp & Dohme, Novartis, Replimune, and Roche; received meeting or travel support from Merck Sharp & Dohme, Pfizer, and Sanofi; and participated on a consulting or an advisory board for Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, and Sanofi. JJDM performed a consulting or advisory role for Bristol Myers Squibb and Medarex. SD received research funding from Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre; received honoraria from Bristol Myers Squibb and Merck Sharp & Dohme; received meeting or travel support from Bristol Myers Squibb and Merck Sharp & Dohme; participated on a safety monitoring or advisory board for Bristol Myers Squibb and Merck Sharp & Dohme; and discloses a patent pending for Trim 24. AA received honoraria from Almirall, Biontech, Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, and Pierre Fabre; and meeting or travel support from Myers Squibb, Merck Sharp & Dohme, Novartis, and Pierre Fabre. CG-M received consulting fees from Bristol Myers Squibb, Iovance, Merck Sharp & Dohme, Pierre Fabre, Regeneron, and Sun Pharma; honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre; meeting or travel support from Bristol Myers Squibb, Merck Sharp & Dohme, and Pierre Fabre; and institutional support for clinical trials from Amgen, AstraZenecca, Bristol Myers Squibb, Catalyst, Day One Biopharmaceuticals, Dragonfly Therapeutics, Erasca, GlaxcoSmithKline, Herthena, Huyabio, IFX, Immunocore, IO Biotech, Jansen, Kinnate, Merck Sharp & Dohme, Microbiotica, Novartis, Pfizer, Philogen, Pierre Fabre, Regeneron, Replimune, Roche, Sairopa, and Sanofi. BC and SM are employed by Bristol Myers Squibb. CDL, SD, and WJ are employed by and have stock options with Bristol Myers Squibb. GVL received consulting fees from Agenus Inc, Amgen Inc, Array Biopharma, AstraZeneca, Bayer Health Care, BioNTech, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, GI Innovation, Hexal AG (Sandoz Company), Highlight Therapeutics, IO Biotech, Immunocore Ireland Limited, Innovent Biologics USA Inc, Merck Sharp & Dohme (Australia) Pty Limited, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Qbiotics Group Limited, Regeneron Pharmaceuticals, Scancell Limited, and SkylineDX BV; and honoraria from Bristol Myers Squibb and Pierre Fabre.
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