Background: SCLC is a deadly cancer and despite initial 80% response, almost all patients (pts) will relapse and die of this disease. Limited options exist after failure of first line, with a median time to progression (TTP) of around 3.5 months. New therapeutic agents are needed. Lurbinectedin (L) is a new anticancer drug that blocks transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial to assess the efficacy and safety of L in several types of advanced solid tumors, including SCLC, is ongoing. In the SCLC cohort, 15 adult patients without brain metastases, who had received one prior chemotherapy line, were recruited. If at least one confirmed response was observed, recruitment would be increased to 100 patients. The study intervention comprised L 3.2 mg/m² in a 1-hour infusion every 3 weeks. Results: 50 pts were treated and evaluable for efficacy. Median age was 60 years (range, 40-83) and 29 (58%) were males. 45 (80%) had an ECOG of 0/1. 34 pts (68%) had metastatic disease at study entry. 25 (50%) pts had a chemotherapy free interval (CTFI) ≥ 90 days and 22 (44%) had a CTFI < 90 days (unknown in 3). Pts received a median of 5 cycles of therapy (range, 1-18) and a median total dose of 15.9 mg/m² (range, 2.9-58.2). Nineteen pts (38%) had a partial response (PR); among pts with CTFI ≥ 90 days, 52% (13/25) had a PR. Twenty pts (40%) had disease stabilization, 6 of them for > 4 months. Median response duration was (K-M) 5.3 (CI 95% 2.8-8.8) and median progression free survival (PFS) was 4.2 months (CI 95% 2.8-6.3). Median PFS for pts with CTFI ≥ 90 days was 4.7 months 95% CI (3.1-7.4). Myelosuppression was the most common adverse event: 44% neutropenia grade (G) 3/4, 12% febrile neutropenia, and 8% thrombocytopenia G 3/4; 8 pts had dose delay due to neutropenia G2-4, and 10 pts had dose reduced because of neutropenia G4. G-CSF was given to 9 pts. There was one protocol-defined withdrawal due to neutropenia. Conclusions: Lurbinectedin as a single agent shows compelling activity as second line treatment in SCLC, with an acceptable tolerability and manageable safety profile. No unexpected or grade 5 toxicity occurred. Updated results will be presented. Clinical trial information: NCT02454972