No added benefit of relatlimab in the adjuvant melanoma setting

The addition of the LAG-3-blocking antibody relatlimab to nivolumab as adjuvant therapy for participants with resected stage III or IV melanoma did not improve recurrence-free survival (RFS) compared with nivolumab alone, in the phase 3 RELATIVITY-098 trial.

Adjuvant anti-PD-1 therapy is the current standard-of-care for resected stage III/IV melanoma. However, the 5-year RFS rate remains at 50%, highlighting the need for further improvement [1]. In the setting of advanced (unresected) stage III/IV melanoma, the combination of relatlimab and nivolumab has previously been shown to significantly improve both progression-free and overall survival (OS) [2].

The RELATIVITY-098 trial (NCT05002569) evaluated the efficacy and safety of nivolumab combined with relatlimab as adjuvant therapy for participants with resected stage III or IV melanoma. The primary endpoint was RFS, with key secondary endpoints including OS and safety. Dr Georgina Long (Melanoma Institute Australia) presented the findings [3]. A total of 1,093 participants were randomised 1:1 following surgery to receive either the relatlimab-nivolumab combination or nivolumab monotherapy, administered for up to 1 year or until disease recurrence, unacceptable toxicity, or death.

After 24 months of follow-up, RFS was similar between the study arms: 64% in the combination arm versus 62% in the monotherapy arm (HR 1.01; 95% CI 0.83–1.22); P=0.928). Similarly, 2-year distant metastasis-free survival was not improved by the combination, reported as 76% with relatlimab-nivolumab and 73% with nivolumab alone (HR 1.07; 95% CI 0.84–1.36).

An exploratory biomarker analysis revealed a greater increase in circulating LAG-3-positive CD8 cells from baseline in participants with unresected stage III/IV melanoma than in those with resected disease. “This suggests that the presence of the tumour tissue may be necessary for optimal efficacy of relatlimab-nivolumab,” concluded Dr Long.

1. Larkin J, et al. Clin Cancer Res. 2023;29:3352-3361.
2. Long GV, et al. NEJM Evid. 2023;2:EVIDoa2200239.
3. Long GV, et al. Nivolumab plus relatlimab vs nivolumab alone for the adjuvant treatment of completely resected stage III–IV melanoma: Primary results from RELATIVITY-098. LBA9500, ASCO Annual Meeting 2025, 30 May-3 June, Chicago, IL, USA.

Medical writing support was provided by Dr Marten Dooper.
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Posted on 5 June 20255 June 2025