Five-year results of a phase 3 trial of addition of relatlimab to nivolumab for advanced melanoma

Nivolumab plus relatlimab is approved for advanced melanoma based on the RELATIVITY-047 trial; however, long-term data are needed. Five-year results of RELATIVITY-047 have now been reported. 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. 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 progression-free survival (HR 0.77; 95% CI 0.65-0.92), overall survival (0.78; 0.64-0.95), and melanoma-specific survival (0.71; 0.57-0.88). The safety profile remained consistent with prior reports. Among biomarker-evaluable patients in the PD-L1≥1% subgroup, there was an association between worse outcomes with nivolumab and high peripheral of tumor LAG-3⁺ CD8 cell levels. The addition of relatlimab to nivolumab was associated with a lower prevalence of primary resistance than nivolumab alone. The authors conclude that 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.