Vibostolimab Coformulated with Pembrolizumab Plus Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer

Vibostolimab, an anti–T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) antibody, showed antitumor activity with pembrolizumab in non–small-cell lung cancer. The KEYVIBE-008 study evaluated vibostolimab coformulated with pembrolizumab (vibostolimab/pembrolizumab) plus etoposide and platinum-based chemotherapy (EP) versus atezolizumab plus EP as first-line therapy for extensive-stage small-cell lung cancer. Participants aged ≥18 years with untreated extensive-stage small-cell lung cancer were randomized 1:1 to vibostolimab/pembrolizumab (200 mg each) or atezolizumab (1200 mg) every 3 weeks, with EP and cisplatin/carboplatin for the first four cycles. The primary endpoint was overall survival. The prespecified interim analysis included a non-binding futility analysis of overall survival (futility threshold for actual number of events, P = 0.4816). Four hundred and sixty participants were randomized (both arms, n = 230). Median time from randomization to data cutoff (4 June, 2024) was 16.6 (range 11.3‒26.1) months. The prespecified futility criterion for overall survival was met (hazard ratio 1.26; 95% confidence interval 1.00‒1.59; P = 0.9762). There was no difference in progression-free survival (hazard ratio 1.01; 95% confidence interval 0.82‒1.23) or objective response rates (71.7% with vibostolimab/pembrolizumab vs 74.8% with atezolizumab). Grade ≥3 treatment-related adverse events occurred in 66.8% of participants treated with vibostolimab/pembrolizumab and 57.2% treated with atezolizumab. Immune-mediated adverse events and infusion reactions occurred in 39.3% and 29.7% of participants, respectively. In this interim analysis of vibostolimab/pembrolizumab plus EP versus atezolizumab plus EP as first-line therapy for extensive-stage small-cell lung cancer, the prespecified futility criterion for overall survival was met. Grade ≥3 treatment-related adverse events and immune-mediated adverse events were more frequent with vibostolimab/pembrolizumab versus atezolizumab. Given the overall benefit/risk profile, treatment with vibostolimab/pembrolizumab was discontinued. Clinicaltrials.gov, NCT05224141.