Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial

Based on RELATIVITY-047, nivolumab plus relatlimab is approved for advanced melanoma. Here, to address a current unmet need for more efficacious adjuvant regimens for completely resected melanoma, the phase 3, double-blind RELATIVITY-098 trial compared adjuvant nivolumab plus relatlimab to nivolumab after complete resection of stage III/IV melanoma. Patients were randomized 1:1 to receive nivolumab 480 mg plus relatlimab 160 mg (n = 547) or nivolumab 480 mg (n = 546) intravenously every 4 weeks for ≤1 year; safety populations totaled 543 and 545 patients, respectively. The primary endpoint was recurrence-free survival (RFS), and the key secondary was overall survival; translational endpoints were exploratory. There was no difference in RFS for nivolumab plus relatlimab versus nivolumab (hazard ratio = 1.01; 95% confidence interval: 0.83-1.22; P = 0.928); therefore, overall survival was not tested. Translational data across trials showed lower circulating LAG-3<sup>+</sup> T cells in the adjuvant setting (RELATIVITY-098) versus advanced melanoma (RELATIVITY-047), where LAG-3<sup>+</sup> T cells were enriched in tumor versus blood. The absence of macroscopic tumor and reduced peripheral LAG-3<sup>+</sup> T cells may explain the lack of added benefit of nivolumab plus relatlimab over nivolumab in resected versus metastatic melanoma. ClinicalTrials.gov identifier: NCT05002569 .

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Publication Details

Journal
Nature Medicine
Published
2025-10-18
DOI
https://doi.org/10.1038/s41591-025-04032-8
Citations
3
Primary Topic
Cutaneous Melanoma Detection and Management
Type
article
Field-Weighted Citation Impact
3.14

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article

Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial

Michele Del Vecchio, Hussein A. Tawbi, Sonia Dolfi, Margaret K. Callahan et al.
3 citations
Nature Medicine
Cutaneous Melanoma Detection and Management
3.14
article

Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial

Michele Del Vecchio, Hussein A. Tawbi, Sonia Dolfi, Margaret K. Callahan, Alicia Cheong, Ahmad A. Tarhini, Ioannis Thomas, Andrew Fisher, Bingshu E. Chen, Paolo A. Ascierto, Andréia Cristina de Melo, Dirk Schadendorf, Peter Koelblinger, Mark Semaan, Eva Muñoz‐Couselo, Jun Guo, Georgina Venetia Long, Bonnie Wang, Charlie Garnett‐Benson, Reinhard Dummer, Gaelle Quereux, Armand Chouzy, Helen J Gogas, Patrick Djidel, Jia Xin Yu, Sunandana Chandra
article en
3 citations

Abstract

Based on RELATIVITY-047, nivolumab plus relatlimab is approved for advanced melanoma. Here, to address a current unmet need for more efficacious adjuvant regimens for completely resected melanoma, the phase 3, double-blind RELATIVITY-098 trial compared adjuvant nivolumab plus relatlimab to nivolumab after complete resection of stage III/IV melanoma. Patients were randomized 1:1 to receive nivolumab 480 mg plus relatlimab 160 mg (n = 547) or nivolumab 480 mg (n = 546) intravenously every 4 weeks for ≤1 year; safety populations totaled 543 and 545 patients, respectively. The primary endpoint was recurrence-free survival (RFS), and the key secondary was overall survival; translational endpoints were exploratory. There was no difference in RFS for nivolumab plus relatlimab versus nivolumab (hazard ratio = 1.01; 95% confidence interval: 0.83-1.22; P = 0.928); therefore, overall survival was not tested. Translational data across trials showed lower circulating LAG-3<sup>+</sup> T cells in the adjuvant setting (RELATIVITY-098) versus advanced melanoma (RELATIVITY-047), where LAG-3<sup>+</sup> T cells were enriched in tumor versus blood. The absence of macroscopic tumor and reduced peripheral LAG-3<sup>+</sup> T cells may explain the lack of added benefit of nivolumab plus relatlimab over nivolumab in resected versus metastatic melanoma. ClinicalTrials.gov identifier: NCT05002569 .

Nature MedicineVol. 31(12)
Northwestern University (US), Hebron University (PS), Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), National and Kapodistrian University of Athens (GR), Peking University (CN), University of Zurich (CH), Paracelsus Medical University (AT), Royal North Shore Hospital (AU), Moffitt Cancer Center (US), Bristol-Myers Squibb (United States) (US), Peking University Cancer Hospital (CN), Vall d'Hebron Institut de Recerca (ES), Sensap (Greece) (GR), Melanoma Institute Australia (AU), Essen University Hospital (DE), Bristol-Myers Squibb (United Kingdom) (GB), Vall d'Hebron Hospital Universitari (ES), Centre d'Investigation Clinique de Nantes (FR), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Instituto Nacional de Câncer - INCA (BR), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), West German Heart and Vascular Center Essen (DE), University of Duisburg-Essen (DE)
Bristol-Myers Squibb, Pfizer, Sanofi, Hexal AG, Regeneron Pharmaceuticals, Merck KGaA, Les Laboratories Pierre Fabre, Incyte, Innovent Biologics, SkylineDx, Bayer HealthCare, University of Sydney, Ono Pharmaceutical, Sun Pharma, Menarini Group, Italfarmaco, Melanoma Institute Australia, Genentech
Openalex Percentile: Top 7%
Cutaneous Melanoma Detection and Management
3.14
DOIOpen Access PDFOpenAlex
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