Multicenter phase 1b study of izalontamab brengitecan in extensive-stage small cell lung cancer

Limited treatment options beyond frontline chemo-immunotherapy are available for small cell lung cancer (SCLC). Izalontamab brengitecan (iza-bren) is a first-in-class bispecific antibody-drug conjugate targeting EGFR and HER3. A multicenter, dose-expansion phase 1b trial in China evaluated iaz-bren for extensive-stage (ES)-SCLC. The study enrolled 52 patients who had progressed on prior systemic therapy. The patients received iza-bren 2.5 mg/kg on days 1 and 8 of 3-week cycles. Primary enpoints were objective response rate (ORR) and safety/tolerability. Among all patients (A-C) and patients who received only one prior line of systemic therapy (n=20; D-F) the ORR was 48.1% (95% CI 34.0-62.4) and 72.7% (49.8-89.3), respectively, with median progression-free survival 4.1 months (3.0-5.5) and 6.2 months (3.7-8.2), respectively, and median overall survival of 12.2 months (9.1-13.2) and 15.0 months (8.7-NR), respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, anemia, and leukopenia. The authors conclude that iza-bren showed encouraging antitumor activity in relapsed ES-SCLC, particularly in the second-line setting.