ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Unraveling Relatlimab-Specific Biology Using Biomarker Analyses in Patients with Advanced Melanoma in RELATIVITY-047.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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The trial behind it
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Who cites it
6 citing papers in PubMed.
- Adjuvant nivolumab and relatlimab in stage III/IV melanoma: the randomized phase 3 RELATIVITY-098 trial.Nature medicine · 2025Trial
- Review
- Tobemstomig, a Novel Bispecific Antibody, Preferentially Blocks PD-1 and LAG-3 on CD8 TILs to Expand Stem-like T Cells for Sustained Tumor Control.Cancer research communications · 2026Article
- Predicting Response to Immune Checkpoint Inhibitors in Melanoma: Emerging Approaches in Digital Pathology, Spatial Profiling and Machine Learning.International journal of molecular sciences · 2026Review
- SLA2 is Associated With Immune evasion and Exhaustion of CD8Journal of cellular and molecular medicine · 2026Article
- Complete Response to Nivolumab-Relatlimab Following Progression of Invasive Sinonasal Mucosal Melanoma on First-Line Nivolumab-Ipilimumab: A Case Report.Cancer reports (Hoboken, N.J.) · 2026Article
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Authors and funding
21 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAdministration of the lymphocyte activation gene 3 (LAG-3) inhibitor relatlimab (RELA) and the PD-1 inhibitor nivolumab (NIVO) significantly prolonged progression-free survival (PFS) versus NIVO alone in patients with advanced melanoma treated in RELATIVITY-047. This report describes correlative analyses of biospecimens collected within that trial to better understand the mechanisms of action and identify patients who could benefit from treatment with NIVO + RELA. PATIENTS AND
methodsPre- and on-treatment peripheral blood samples from 563 patients were analyzed using flow cytometry for changes in 77 prespecified immune cell populations and using immunoassay for peripheral IFNγ. Pretreatment tumor biopsies were evaluated using IHC and RNA sequencing.
resultsOn-treatment expansion of 25 peripheral immune cell populations was significantly greater with NIVO + RELA versus NIVO alone. Responders to NIVO + RELA had greater on-treatment increases in LAG-3+CD4+ T cells than nonresponders. Significantly greater increases in peripheral IFNγ occurred after treatment with NIVO + RELA versus NIVO alone. A longer PFS was observed in patients treated with NIVO + RELA whose tumors had low CD8 expression compared with the NIVO arm. When evaluating the co-expression of CD8 and LAG-3, patients whose tumors had high CD8+LAG-3+ also showed a PFS benefit with NIVO + RELA versus NIVO. RNA sequencing revealed several distinct gene signatures associated with response to NIVO + RELA.
conclusionsThese results highlight the unique biological effects of RELA in combination with NIVO and provide further understanding of the patient characteristics associated with increased benefit from NIVO + RELA.
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