Summary
A prespecified five-year analysis of RELATIVITY-047 found lower hazards of progression and death with relatlimab plus nivolumab than with nivolumab alone. Exploratory biomarker analyses also linked higher LAG-3-positive CD8 cell levels to worse outcomes on nivolumab in a defined subgroup.
A prespecified five-year analysis of the RELATIVITY-047 trial found that people with metastatic or unresectable melanoma assigned to relatlimab plus nivolumab had lower hazards of disease progression and death than those assigned to nivolumab alone. The peer-reviewed analysis, published in Nature Medicine on 24 October 2026, included a minimum follow-up of 57.3 months.
The trial randomly assigned 714 patients: 355 received nivolumab 480 mg plus relatlimab 160 mg, and 359 received nivolumab 480 mg. Both treatments were given intravenously every four weeks. The study was double-blind; its primary endpoint was progression-free survival assessed by blinded independent central review. Overall survival, response and safety were secondary endpoints.
Survival outcomes after extended follow-up
Compared with nivolumab alone, the combination had a hazard ratio of 0.77 for progression-free survival (95% confidence interval, 0.65–0.92) and 0.78 for overall survival (95% confidence interval, 0.64–0.95). A post-hoc analysis of melanoma-specific survival reported a hazard ratio of 0.71 (95% confidence interval, 0.57–0.88).
A hazard ratio below 1 indicates a lower rate of the measured event in the combination group over the follow-up period. These figures describe relative hazards, not the percentage-point difference in how many patients were alive or progression-free at five years. The study abstract reports that the survival curves remained separated and describes the benefit as clinically significant; it does not provide absolute survival percentages in the reported summary.
Nivolumab blocks PD-1, an immune checkpoint that can limit T-cell activity. Relatlimab targets another checkpoint, LAG-3. Combining the drugs is intended to inhibit these two pathways. The longer follow-up adds evidence about the durability of the combination’s advantage over nivolumab alone in this trial population.
Biomarker findings and their scope
The researchers also examined biomarkers, including in patients whose tumours had PD-L1 expression of at least 1%. Among biomarker-evaluable patients in that subgroup, higher levels of LAG-3-positive CD8 cells in blood or tumour were associated with worse outcomes on nivolumab. The paper also reports a lower prevalence of primary resistance—when a treatment fails to control the cancer from the outset—with the combination than with nivolumab alone.
These analyses were exploratory. They support the researchers’ hypothesis that adding LAG-3 blockade may help address resistance associated with LAG-3, but the reported associations do not by themselves establish a biomarker test for selecting treatment. The findings describe patterns within the trial and should be read alongside its main randomized comparison. The authors report that the combination’s safety profile remained consistent with earlier reports.