Relatlimab plus nivolumab versus nivolumab for advanced melanoma: 5-year survival and biomarker analyses of the phase 3 RELATIVITY-047 trial
In brief
Adding relatlimab lowers the death hazard by about 22% in advanced melanoma
After at least 4.8 years of follow-up, patients given nivolumab plus relatlimab had about 22% lower hazard of death and 23% lower hazard of disease progression than those given nivolumab alone. Safety remained consistent with earlier reports; exploratory biomarker findings suggest relatlimab may help counter treatment resistance, but need further validation.
- Journal
- Nature medicine (Q1)
- Published
- 24 October 2026
- Study design
- Phase 2 randomized trial (exploratory)
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Georgina V Long, Sonia Dolfi, F Stephen Hodi, Evan J Lipson, Dirk Schadendorf, Paolo A Ascierto, et al.
- PMID
- 42926136
- DOI
- 10.1038/s41591-026-04756-1
Why clinicians should know about it
- Picked for Dermatology (paper of the day, 26 October 2026): Long-term phase III evidence for advanced melanoma therapy
Abstract
Nivolumab plus relatlimab is approved for advanced melanoma based on the RELATIVITY-047 trial; however, long-term data are needed. Here, we report data from RELATIVITY-047 with the longest follow-up at present. In this phase 2-3, double-blind trial, patients with metastatic/unresectable melanoma were randomized 1:1 to nivolumab 480 mg plus relatlimab 160 mg (n = 355) or nivolumab 480 mg (n = 359) intravenously every 4 weeks. The primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints were overall survival (OS), response, and safety. Additional post-hoc analyses such as melanoma-specific survival (MSS), and exploratory biomarker analyses are also reported. This analysis shows clear separation in survival curves with the largest absolute differences to date in PFS, OS, and MSS. In this prespecified 5-year analysis, with a minimum follow-up of 57.3 months, nivolumab plus relatlimab demonstrated continued clinically significant benefit versus nivolumab for PFS (hazard ratio = 0.77; 95% confidence interval: 0.65-0.92), OS (hazard ratio = 0.78; 95% confidence interval: 0.64-0.95), and MSS (hazard ratio = 0.71; 95% confidence interval: 0.57-0.88). The safety profile remained consistent with prior reports. Among biomarker-evaluable patients in the programmed death ligand 1 ≥1% subgroup, analyses revealed an association between worse outcomes with nivolumab and high peripheral or tumor lymphocyte activation gene 3 (LAG-3)+ CD8 cell levels. The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone. These data support the hypothesis that relatlimab can overcome LAG-3-mediated resistance to nivolumab and provides evidence for differential efficacy patterns observed across biomarker subgroups linked to primary versus acquired resistance states. ClinicalTrials.gov identifier: NCT03470922.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.