Nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in stage IV or recurrent non-small cell lung cancer: clinical, translational, and patient-reported outcomes results from the phase II RELATIVITY-104 study

BACKGROUND: Programmed death 1-blocking antibody, nivolumab, plus lymphocyte-activation gene 3-blocking antibody, relatlimab, is approved for advanced melanoma. We report results from Part 2 of RELATIVITY-104, the first phase II, proof-of-concept, head-to-head study to evaluate first-line nivolumab plus relatlimab plus platinum doublet chemotherapy (PDCT) versus nivolumab plus PDCT in patients with stage IV/recurrent non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: In Part 2, 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). Secondary endpoints included progression-free survival (PFS) and duration of response (DOR) per BICR, ORR and PFS by subgroups, and safety. Exploratory analyses included overall survival (OS), biomarker, translational, and patient-reported outcomes. RESULTS: In part 2, the primary endpoint was not met (ORR, 51.3% for nivolumab plus relatlimab plus PDCT versus 45.0% for nivolumab plus PDCT); PFS hazard ratio (HR; 90% confidence interval [CI]) was 0.89 (0.72 to 1.09). A trend towards improved clinical benefit was seen with nivolumab plus relatlimab plus PDCT in a subgroup of patients with programmed death ligand 1 (PD-L1) ≥1% and nonsquamous histology (ORR: 58.0% versus 39.6%; PFS: HR, 0.68; 90% CI 0.46 to 1.01). A potential improvement in OS was observed with nivolumab plus relatlimab plus PDCT in the PD-L1 ≥1% nonsquamous subgroup (HR, 0.60; 90% CI 0.38 to 0.94). The safety profile of nivolumab plus relatlimab plus PDCT was manageable and consistent with previous reports. CONCLUSION: In RELATIVITY-104, the addition of relatlimab to standard-of-care did not 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 III RELATIVITY-1093 study. CLINICALTRIALS: gov identifier: NCT04623775.