Nivolumab Plus Relatlimab Maintains PFS and OS Advantage Over Nivolumab in Advanced Melanoma

After 5 years of follow-up, nivolumab plus relatlimab continued to show longer progression-free survival (PFS) and overall survival (OS) than nivolumab alone in patients with previously untreated advanced melanoma, according to updated RELATIVITY-047 results published in Nature Medicine as an accelerated article preview and presented at the European Society for Medical Oncology Congress 2026.

According to the authors, nivolumab plus relatlimab is approved for advanced melanoma based on RELATIVITY-047, but long-term data were needed. Relatlimab blocks lymphocyte activation gene 3 (LAG-3), an inhibitory immune checkpoint distinct from programmed cell death protein 1.

In the phase 2-3, double-blind trial, 714 patients with previously untreated, unresectable stage III or IV melanoma were randomly assigned 1:1 to a fixed-dose combination of nivolumab 480mg and relatlimab 160mg or to nivolumab 480mg, given intravenously every 4 weeks. At a minimum follow-up of 57.3 months, median PFS by blinded independent central review, the primary endpoint, was 10.2 months with the combination and 4.6 months with nivolumab (hazard ratio, 0.77; 95% CI, 0.65-0.92); 5-year PFS rates were 29% and 19%. Median OS was 54.8 vs 33.2 months (hazard ratio, 0.78; 95% CI, 0.64-0.95), with 5-year OS rates of 48% vs 38%. In a post hoc analysis, 5-year melanoma-specific survival was 58% vs 45%.

Grade 3 or 4 treatment-related adverse events occurred in 22.5% vs 12.3% of patients, and no new treatment-related deaths were reported since the initial OS analysis. Among patients with tumor cell programmed death ligand 1 expression of 1% or higher, OS curves began to separate at about 3 years; median OS was 80.3 vs 42.0 months, although the confidence interval included no difference (hazard ratio, 0.81; 95% CI, 0.59-1.11). In exploratory analyses in this subgroup, high peripheral or tumor LAG-3-positive CD8 T-cell levels were associated with worse outcomes with nivolumab, and adding relatlimab was associated with less primary resistance.

The authors said the 5-year analyses were descriptive and the biomarker analyses were exploratory, not powered for formal comparisons, and hypothesis-generating. 

Source: Long GV, Dolfi S, Hodi FS, et al. Relatlimab plus nivolumab versus nivolumab for advanced melanoma: 5-year survival and biomarker analyses of the phase 3 RELATIVITY-047 trial. Nat Med. Published online October 24, 2026. doi:10.1038/s41591-026-04756-1