Relatlimab (LAG-3) + Nivolumab/Platinum Chemo Expands LAG-3⁺ Memory T Cells and Cuts Risk of Progression 45% in PD-L1 ≥1% Non-Sq NSCLC

In the Phase 2 RELATIVITY-104 study (NCT04623775), 1L metastatic NSCLC patients received nivolumab (PD-1 checkpoint inhibitor) + platinum-doublet chemotherapy with or without high-dose relatlimab (anti-LAG-3 monoclonal antibody). Pharmacodynamic blood profiling showed only the relatlimab arm expanded proliferating LAG-3-expressing effector/central-memory CD4⁺/CD8⁺ T cells. Among non-squamous tumors with PD-L1 ≥1% (n ≈ 50/48), relatlimab boosted ORR to 58% vs 40%, while benefit disappeared in PD-L1 <1% disease (HR 1.24). Baseline tumor LAG-3 ≥1% correlated with numerically higher response in both arms, yet even LAG-3-low tumors gained similar PFS from relatlimab (HR 0.79 vs 0.81). Squamous subsets had a limited sample size and no clear predictive pattern.