Abstract
BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC) often recurs after platinum-based chemotherapy, with limited second-line options. This phase II trial evaluated the efficacy and safety of tislelizumab combined with anlotinib and irinotecan as second-line therapy for ES-SCLC. METHODS: In this single-arm, open-label phase II trial (NCT05027100) conducted in China, patients with ES-SCLC who progressed after first-line platinum-based chemotherapy were enrolled. Patients received tislelizumab (200 mg intravenously every 3 weeks), anlotinib (10 mg orally, days 1-14), and irinotecan (100 mg/m(2) intravenously, days 1 and 8) for two 21-day cycles, followed by maintenance with tislelizumab and anlotinib until progression or intolerable toxicity. Tumor response was assessed every six weeks using the response evaluation criteria in solid tumors (RECIST) v1.1. The primary endpoint was objective response rate (ORR), with secondary endpoints including progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. FINDINGS: Between September 2021 and March 2024, 32 patients were enrolled. At a median follow-up of 9.6 months (IQR: 7.4-21.9), ORR was 50% (16/32, 95% CI: 32%-68%), median PFS was 7.1 months (95% CI: 3.1-9.9), and median OS was 7.5 months (95% CI: 5.3-11.0). Grade ≥3 treatment-related adverse events occurred in 25% (8/32) of patients, with two grade ≥3 immune-related events. INTERPRETATION: Tislelizumab, anlotinib, and irinotecan demonstrated promising efficacy and manageable toxicity as second-line therapy for ES-SCLC post-platinum-based chemotherapy or immune checkpoint inhibitors. FUNDING: This work was supported by the Guangzhou Key Laboratory of Acupuncture and Medicine Research, Beijing Health Alliance Charitable Foundation, the National Key Research and Development Program of China (2023YFC3503303), and Major Scientific and Technological Projects of Chinese Medicine in Guangzhou area (2025ZD007).