A phase II, multicenter, open-label, single-arm study of berzosertib plus topotecan in patients with relapsed platinum-resistant small-cell lung cancer (DDRiver SCLC 250)

作者：Alejandro Navarro, Anish Thomas, Y. Cheng, Yuanbin Chen, N. Reguart, T. Yoshida, Sophie Cousin, Xiang Da Dong, N. Yamamoto, Federico Cappuzzo, R. Hallwachs, Jayaprakasam Bolleddula, B. Sarholz, Thomas Grombacher, M. Otte, Ioannis Gounaris, Jaume Ferrer, Camilo Moulin, Luis Paz‐Ares · 发表于：ESMO Open · 年份：2025 · DOI：10.1016/j.esmoop.2025.105918 · 研究领域：Lung Cancer Research Studies、Cancer therapeutics and mechanisms、Multiple Myeloma Research and Treatments

BACKGROUND: Small-cell lung cancer (SCLC) is characterized by high genomic instability. Proteins involved in maintaining genomic stability, such as ataxia telangiectasia and Rad3-related (ATR) and topoisomerase 1, are promising therapeutic targets in SCLC. Berzosertib, a highly potent, selective, intravenously administered ATR inhibitor, has demonstrated promising antitumor activity in patients with platinum-resistant SCLC. MATERIALS AND METHODS: on days 1-5) intravenously in 21-day cycles until disease progression. Primary endpoints were objective response rate (ORR per RECIST v1.1), assessed by an Independent Review Committee. Key secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: A preplanned interim analysis for futility after the first 40 patients had completed their second on-treatment tumor assessment (or dropped out/died prematurely) revealed a low probability of reaching the predefined efficacy threshold, leading to premature study termination. At the final analysis (n = 73), four patients achieved confirmed partial response, resulting in an ORR of 5.5%. The median PFS was 2.2 months [95% confidence interval (CI) 1.5-2.7 months], and the median OS was 6.4 months (95% CI 4.2-7.6 months). No new safety concerns were observed, with the safety profile of berzosertib and topotecan combination therapy being consistent with the known risk profile of the respective monotherapies. CONCLUSIONS: No added clinical benefit of...