berzosertib + topotecan

**Berzosertib + topotecan** is an investigational combination therapy for relapsed small cell lung cancer (SCLC) and related neuroendocrine tumors. Berzosertib is a potent inhibitor of ataxia telangiectasia and Rad3-related kinase (ATR), which plays a critical role in the DNA damage response; topotecan is a topoisomerase I inhibitor, approved as a chemotherapy agent for SCLC. The combination seeks to exploit the heightened replication stress in SCLC, with berzosertib potentiating the cytotoxic effects of topotecan by blocking DNA repair in tumor cells. Multiple phase 1 and 2 studies have shown this combination achieves tumor shrinkage and durable responses, including in platinum-resistant cancers, but progression-free survival benefit was not confirmed over topotecan alone in a phase 2 randomized trial, though overall survival was improved[1][2][3][4][6][7].