Trial reportJournal for immunotherapy of cancer2025
Effect of prior and first-line immunotherapy on baseline immune biomarkers and modulation of the tumor microenvironment in response to nivolumab and relatlimab combination therapy in patients with melanoma from RELATIVITY-020.
Trial report in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01968109 (A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody), which is not on this map. Cited by 4 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I/2a Dose Escalation and Cohort Expansion Study of the Safety, Tolerability, and Efficacy of Anti-LAG-3 Monoclonal Antibody (BMS-986016) Administered Alone and in Combination With Anti-PD-1 Monoclonal Antibody (Nivolumab, BMS-936558) in Advanced Solid Tumors
Who cites it
4 citing papers in PubMed.
- Inhibitory receptor profiles for joint prediction of benefit and toxicity in immune checkpoint blockade.iScience · 2026Review
- Predicting Response to Immune Checkpoint Inhibitors in Melanoma: Emerging Approaches in Digital Pathology, Spatial Profiling and Machine Learning.International journal of molecular sciences · 2026Review
- Bridging the Gap: Incorporating Lifileucel Into Management of Advanced PD-1 Blockade Resistant Melanomas.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Article
- Overcoming resistance to anti-PD-L1 immunotherapy: mechanisms, combination strategies, and future directions.Molecular cancer · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors.
Funding
Abstract
backgroundSome patients with melanoma experience disease progression during immunotherapy (IO) and may benefit from novel combinations of immune checkpoint inhibitors (ICIs). We report results from exploratory biomarker analyses to characterize the responses of patients with advanced melanoma to treatment with nivolumab (anti-programmed cell death-1 (PD-1)) and relatlimab (anti-lymphocyte-activation gene 3 (LAG-3)) combination therapy in RELATIVITY-020 (NCT01968109).
methodsTumor biopsies collected at baseline and ≤4 weeks after treatment initiation were evaluated for % LAG-3-positive and % CD8-positive immune cells and % programmed death-ligand 1 (PD-L1) expression on tumor cells. Baseline biomarker expression was compared among patients with IO-refractory melanoma based on last prior therapy and IO-resistance type, and between patients with IO-refractory and IO-naïve melanoma. Change in biomarker expression after treatment was evaluated in patients with IO-refractory and IO-naïve melanoma. Immune-related gene expression was compared among resistance groups and by the last prior treatment.
resultsAmong patients with IO-refractory melanoma (N=505), elevated baseline LAG-3, PD-L1, and CD8 expression (p≤0.01, p≤0.05, p≤0.001, respectively) was observed in patients whose last prior therapy was IO versus non-IO, and in those who responded (complete/partial per Response Evaluation Criteria in Solid Tumors V.1.1) to nivolumab and relatlimab combination therapy versus those who did not (stable/progressive disease). Inflammation-related gene expression was significantly higher (p<0.05) in patients with secondary versus primary resistance to prior IO treatment, and in those whose last prior therapy was IO versus non-IO. IO-refractory patients whose tumors responded to nivolumab and relatlimab combination therapy had higher inflammation-related gene expression than non-responders (p<0.05); proliferation and hypoxia-related gene expression were enriched in non-responders. During treatment with nivolumab and relatlimab combination therapy, LAG-3 expression increased significantly in patients with IO-refractory (p≤0.01) and IO-naïve melanoma (p≤0.001), and PD-L1 and CD8 increased significantly (p≤0.01 and p≤0.05, respectively) in patients with IO-naïve melanoma.
conclusionsNivolumab and relatlimab combination therapy can modulate the tumor microenvironment in patients with both IO-refractory and IO-naïve melanoma. Further research is needed to identify patients who will most benefit from anti-LAG-3/PD-(L)1 agents, and to elucidate the mechanisms of action of, and resistance to, this combination therapy in patients with advanced melanoma. TRIAL REGISTRATION NUMBER: NCT01968109.
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