ASCO 2025 | RELATIVITY-098: nivolumab and relatlimab in stage III-IV melanoma

So this ASCO 2025, I presented the results of the Phase 3 RELATIVITY-098 trial. This is a randomized trial of nivolumab combined with relatlimab, an anti-LAG3 checkpoint inhibitor versus nivolumab alone for resected stage 3 or stage 4 melanoma. Predominantly, patients had stage 3 melanoma. Now, why did we do this study? First of all, we saw positive results in the advanced melanoma setting in the RELATIVITY-047 trial, which was nivolumab combined with relatlimab versus nivolumab in advanced melanoma with a strongly significant improvement in the progression-free survival and later in time the overall survival for patients who had the combination over nivolumab alone. So that was one part of the rationale. The other part of the rationale is the standard of care for resected stage 3 or 4 melanoma in the adjuvant setting is anti-PD-1 alone. So nivolumab alone has a five-year recurrence-free survival landmark of 50%, much better than no treatment. However, we do need to do better than that. So hence the RELATIVITY-098 trial. What we saw, though, for the primary endpoint of recurrence-free survival was a negative trial. The hazard ratio was 1.01 and the p-value 0.928, meaning the combination of nivolumab and relatlimab did not improve the recurrence-free survival over nivolumab alone. The next question is why? So looking at translational biomarkers, we see that it may be that we need the tumor on board to have our best effect when we’re adding LAG3. So what does that mean for the future? It means that in likelihood, combination therapy with an anti-LAG3 will be best served in the neoadjuvant setting when we have tumor on board or the advanced setting. Nivolumab and relatlimab in combination does not improve the relapse-free survival in the adjuvant setting, so it should not be used in that setting.

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