Phase 2 Open-Label Study of Sacituzumab Govitecan as Second-Line Therapy in Patients With Extensive-Stage SCLC: Results From TROPiCS-03

INTRODUCTION: The phase 2 TROPiCS-03 study evaluated the efficacy/safety of sacituzumab govitecan (SG) as second-line treatment in patients with previously treated extensive-stage SCLC (ES-SCLC). METHODS: TROPiCS-03 (NCT03964727) is a multicohort, open-label, phase 2 basket study of solid tumors, including ES-SCLC. Adults with ES-SCLC that progressed after one previous line of platinum-based chemotherapy and anti-programmed death-(ligand) 1 (PD-[L]1) therapy received SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary end point was the investigator-assessed objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary end points included investigator-assessed duration of response (DOR) and progression-free survival (PFS); blinded independent central review-assessed ORR, DOR, and PFS; overall survival (OS); and safety. Efficacy was evaluated in patients with platinum-resistant and platinum-sensitive disease. RESULTS: Among 43 patients (median follow-up, 12.3 [range, 8.1-20.1] mo), investigator-assessed ORR was 41.9% (95% confidence interval [CI]: 27.0%-57.9%), with 18 confirmed partial responses; median (95% CI) DOR, PFS, and OS were 4.73 (3.52-6.70), 4.40 (3.81-6.11), and 13.60 (6.57-14.78) months, respectively. The efficacy results of the blinded independent central review assessments were similar. The investigator-assessed ORR (95% CI) was 35.0% (15.4%-59.2%) in patients with platinum-resistant disease (n = 20) and 47.8% (26.8%-69.4%) in patients with platinum-sensitive disease (n = 23). Furthermore, 32 patients (74.4%) had grade greater than or equal to 3 treatment-emergent adverse events (TEAEs). No TEAE led to SG discontinuation; one treatment-related TEAE (neutropenic sepsis) led to death. CONCLUSIONS: SG has promising efficacy as second-line treatment of ES-SCLC, irrespective of platinum sensitivity. Safety was manageable and consistent with that observed in other SG studies.