KEYNOTE‐025: Phase 1b study of pembrolizumab in Japanese patients with previously treated programmed death ligand 1–positive advanced non–small‐cell lung cancer

Pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD‐1), has been shown to improve overall survival (OS) in patients with previously treated advanced non–small‐cell lung cancer (NSCLC) with programmed death ligand 1 (PD‐L1) tumor proportion score (TPS) ≥1%. We report safety and efficacy results from the phase 1b KEYNOTE‐025 study, which evaluated pembrolizumab in Japanese patients with previously treated NSCLC. Eligible patients had histologically/cytologically confirmed advanced NSCLC with PD‐L1 TPS ≥1% and had received ≥1 platinum‐doublet chemotherapy. Patients received pembrolizumab 10 mg/kg once every 3 weeks for 2 years or until disease progression/unacceptable toxicity. Primary objectives were to evaluate the safety of pembrolizumab in patients with PD‐L1 TPS ≥1% and the objective response rate (ORR) per RECIST version 1.1 in patients with PD‐L1 TPS ≥50%. Thirty‐eight patients were enrolled and received ≥1 pembrolizumab dose. The median (range) age was 66.0 (41‐78) years, and 61% had received ≥2 prior systemic therapies. Eleven patients (29%) experienced grade 3‐5 treatment‐related adverse events (AE); 9 patients (24%) experienced immune‐mediated AE and infusion reactions, with pneumonitis (11%; any grade) being most common. Among evaluable patients with PD‐L1 TPS ≥50% (n = 11), ORR was 27% (95% CI, 6‐61). Among evaluable patients with PD‐L1 TPS ≥1% (n = 37), ORR was 22% (95% CI, 10‐38). Median (95% CI) progression‐free survival and OS were 3.9 (2.0‐6.2) months and 19.2 (8.0‐26.7) months, respectively. In summary, pembrolizumab was generally well tolerated and showed promising antitumor activity in Japanese patients with previously treated PD‐L1–expressing NSCLC. Outcomes were consistent with those from the phase 3 KEYNOTE‐010 study. (Trial registration number: ClinicalTrials.gov, NCT02007070.)