No added benefit of relatlimab in the adjuvant melanoma setting

The addition of the lymphocyte activation gene 3 (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, according to the phase 3 RELATIVITY-098 trial.

Adjuvant anti-programmed cell death protein-1 (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 treatment improvement [1]. In the setting of advanced (unresectable) stage III/IV melanoma, the combination of relatlimab and nivolumab demonstrated significantly improved progression-free survival and overall survival [2]. Following up on that, the presented RELATIVITY-098 trial (NCT0500569) 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 overall survival and safety. Prof. Georgina Long (Melanoma Institute Australia, 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, reaching 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).

Hinting at a potential explanation for the absent benefit, a parallel exploratory biomarker analysis revealed a greater increase in circulating LAG-3-positive CD8+ T cells from baseline in participants with unresectable stage III/IV melanoma compared to those with resected disease (see Figure). “This suggests that the presence of the tumour tissue may be necessary for optimal efficacy of relatlimab-nivolumab,” concluded Prof. Long.

Figure: CD8⁺ T cell subtype delta change in advanced unresectable versus resected melanoma treated with nivolumab with and without relatlimab addition [3]



LAG-3, lymphocyte activation gene 3; NIVO, nivolumab; ns, not significant; PD-1, programmed cell death protein-1; RELA, relatlimab.

1. Larkin J, et al. Clin Cancer Res. 2023;29(17):3352–3361.
2. Long GV, et al. NEJM Evid. 2023;2(4):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 the RELATIVITY-098. Abstract LBA9500, ASCO Annual Meeting 2025, May 30–June 3, Chicago, IL, USA.

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Posted on 30 July 2025