Multinational phase 2 trial of adding relatlimab to nivolumab plus chemotherapy for stage IV or recurrent non-small cell lung cancer

Nivolumab (PD-1 blockade) plus relatlimab (LAG-3 blockade) is approved for advanced melanoma. Part 2 of the multinational randomized phase 2 RELATIVITY-104 trial evaluated addition of relatlimab to first-line nivolumab plus platinum doublet chemotherapy (PDCT) in patients with stage IV or recurrent non-small cell lung cancer (NSCLC). In part 2 (n=309; median follow-up 10.7 months), patients were randomized 1:1 to nivolumab plus relatlimab plus PDCT or nivolumab plus PDCT. The primary endpoint was objective response rate (ORR) per blinded independent central review (BICR). The primary endpoint was not met, with ORR 51.3% for nivolumab plus relatlimab plus PDCT versus 45.0% for nivolumab plus PDCT; progression-free survival (PFS) HR was 0.89 (90% CI 0.72-1.09). A trend towards improved clinical benefit was seen with addition of relatlimab to nivolumab plus PDCT in the subgroup of patients with PD-L1 ≥1% and nonsquamous histology (ORR 58.0% versus 39.6%; PFS HR 0.68; 90% CI 0.46-1.01). A potential improvement in overall survival was observed with addition of relatlimab to nivolumab plus PDCT in the PD-L1≥ 1% nonsquamous subgroup (HR 0.60; 90% CI 0.38-0.94). The safety profile of nivolumab plus relatlimab plus PDCT was manageable and consistent with previous reports. The authors conclude that addition of relatlimab to standard-of-care did not significantly improve outcomes in the unselected all-randomized population. However, positive trends observed in the subgroup of patients with tumor PD-L1 ≥ 1% and nonsquamous NSCLC supports further investigation in these patients in the phase 3 RELATIVITY-1093 study.