AdvanTIG-302: Phase 3 Study of Ociperlimab (Anti-TIGIT) Plus Tislelizumab (Anti–PD-1) Versus Pembrolizumab in Untreated, Locally Advanced, Unresectable, or Metastatic NSCLC With PD-L1 Expression of 50% or More

INTRODUCTION: Novel agents that improve outcomes in NSCLC are needed. Co-inhibition of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitor motif domains and programmed cell death protein 1 (PD-1) may enhance anti-PD-1 activity. AdvanTIG-302 is a phase 3 trial of ociperlimab plus tislelizumab (A), pembrolizumab (B), and tislelizumab (C) in first-line stage III/IV NSCLC with programmed cell death-ligand 1 expression of 50% or more (NCT04746924). METHODS: Eligible patients were randomized (5:5:2) to A, B, or C. The primary objective was overall survival (OS) in A versus B; key secondary analyses were progression-free survival (PFS) and overall response rate (ORR). RESULTS: As of May 30, 2025, the prespecified interim analysis (N = 662) was terminated due to futility; efficacy analyses are descriptive only. Median OS (95% confidence interval [CI]) was 31.9 (25.7-not estimable [NE]), 29.4 (25.8-35.0), and 27.7 (20.0-NE) months for arms A, B, and C, respectively; the stratified hazard ratio for A versus B was 0.97 (95% CI: 0.76-1.23). For A, B, and C, median PFS (95% CI) was 14.3 (11.5-16.0), 10.5 (8.4-12.6), and 16.6 (8.9-26.3) months and ORR (95% CI) was 61.0% (55.1-66.7), 48.8% (42.9-54.7), and 55.7% (44.7-66.3), respectively. In arms A, B, and C, treatment-related adverse events occurred in 84.3%, 79.4%, and 79.3% of patients, respectively. CONCLUSION: Ociperlimab plus tislelizumab had no improvement in OS compared with pembrolizumab; median OS was comparable across arms. Data for B versus C should be interpreted cautiously given the descriptive nature of this comparison. The safety profiles of all treatment arms were well tolerated, with no new safety signals.