Multicenter phase 1-2 study of lurbinectedin plus pembrolizumab for relapsed small cell lung cancer

Small cell lung cancer (SCLC) has limited second-line treatment options after chemotherapy. The multicenter phase 1-2 LUPER trial in Spain evaluated the combination of lurbinectedin and pembrolizumab for relapsed SCLC. The recommended phase 2 dose was 3.2 mg/m² lurbinectedin plus 200 mg pembrolizumab every 3 weeks. Phase 2 included 28 patients. The objective response rate per local investigator was 46.4% (95% CI 27.5-66.1) including complete response in 10.7%. The median duration of response was 7.8 months, with 40% maintaining responses for ≥ 12 months. Median progression-free survival was 4.6 months, and median overall survival was 10.5 months. Patients with platinum-sensitive disease (50% of patients) had significantly better PFS (8.0 versus 2.8 months; p=0.012) and numerically better OS (15.7 versus 7.1 months; p=0.058) compared with patients with platinum-resistant disease. Grade ≥ 3 treatment-related adverse events occurred in 71.4% of patients, with transient neutropenia being the most common. The authors conclude that lurbinectedin plus pembrolizumab showed promising efficacy in relapsed SCLC, particularly in patients with platinum-sensitive disease, with a manageable safety profile (graphical abstract).