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

Georgina V. Long, Charlie Garnett-Benson, Sonia Dolfi, Paolo A. Ascierto, Jun Guo, Ahmad A. Tarhini, Sunandana Chandra, Eva Muñoz-Couselo, Michele Del Vecchio, Andreia Cristina de Melo9, Margaret Callahan, Helen Gogas, Reinhard Dummer, Dirk Schadendorf, Peter Koelblinger, Gaelle Quereux, Ioannis Thomas, Jia Xin Yu, Andrew Fisher, Bonnie Wang, Patrick Djidel, Armand Chouzy, Mark Semaan, Bohang Chen, Alicia M. Y. Cheong & Hussein A. Tawbi, Nature medicine, (18 Oct 2025) doi: 10.1038/s41591-025-04032-8.

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+ T cells in the adjuvant setting (RELATIVITY-098) versus advanced melanoma (RELATIVITY-047), where LAG-3+ T cells were enriched in tumor versus blood. The absence of macroscopic tumor and reduced peripheral LAG-3+ T cells may explain the lack of added benefit of nivolumab plus relatlimab over nivolumab in resected versus metastatic melanoma. ClinicalTrials.gov identifier: NCT05002569 .