A phase II, open-label, efficacy and safety of olaparib with bevacizumab (SUKSES-B2) in biomarker matched relapsed or refractory small cell lung cancer.

e20118 Background: The treatment of relapsed or refractory small-cell lung cancer (SCLC) remains challenging due to a paucity of effective options and its rapid proliferation coupled with a high rate of genomic alterations in the DNA damage response (DDR) pathway. The SUKSES-B2 study is designed to assess the efficacy and safety of a PARP inhibitor combined with a VEGF inhibitor within a biomarker-focused umbrella framework. Methods: In this open-label, phase II, multi-cohort umbrella trial, patients received 300mg of olaparib every 12 hours and 15mg/kg of bevacizumab on day 1 of a 21-day cycle. The biomarker based inclusion criteria for SUKSES-B2 arm were as follows: (1) SLFN11 positivity, (2) POU2F3 positivity, (3) DDR pathway alterations, or (4) ATM deficiency. A total of 25 evaluable patients were targeted for recruitment, with the primary endpoint being the objective response rate (ORR). Concurrent biomarker studies were also conducted. Results: Between August 2021 and September 2023, twenty-five patients were enrolled at Samsung Medical Center, South Korea. The median age was 67 (range: 49-80), with the cohort being predominantly male (n = 24) and smokers (n = 23). The Eastern Cooperative Oncology Group Performance Status was 0 (n = 1) or 1 (n = 24) for all participants. Patients were identified to possess following biomarkers: ATM loss (n = 1), SLFN11 expression (n = 18), POU2F3 expression (n = 1), and co-expression of SLFN11 & POU2F3 (n = 5). The ORR was 12.0%, with 3 partial responses. Median progression-free survival was 1.31 months (95% CI: 1.28-5.28) and overall survival was 7.80 months (95% CI: 5.21-9.87). All responders demonstrated 3+ SLFN11 expression with ASCL1 expression. The disease control rate was 48.0%, including nine patients with stable disease, showcasing a PFS range of 2.1 to 6.8 months. Among the patients with stable disease, four patients exhibited tumor volume reductions of 4% to 17%. Drug-related adverse events (AEs) included grade 3 anemia (n = 4) and febrile neutropenia (n = 1); however, the majority of AEs were grade 1 or 2 and were managed with standard treatments. Conclusions: The combination of olaparib and bevacizumab has shown clinical benefits in a subset of patients, particularly those with SLFN11 expression, and was generally well-tolerated. The observed extended duration of response in certain patients suggests the need for further studies. Clinical trial information: NCT04939662 .