BAT8008, a TROP-2 antibody-drug conjugate (ADC), in patients with advanced solid tumor: Results from a phase 1 study.

3024 Background: BAT8008 is a monoclonal ADC that delivers exatecan to cells expressing TROP-2. TROP-2 is a cell surface glycoprotein that can be expressed in certain normal tissue but is frequently overexpressed in multiple carcinomas including cervical cancer (CC) and esophageal cancer (EC). Here we report the safety and efficacy data of BAT8008. Methods: BAT8008 was administered by intravenous infusion at doses of 0.8-2.7mg/kg on days 1 of each14-day cycle(the first cycle is 21-day). The study included dose escalation, dose expansion and cohort expansion which included CC, EC and other solid tumors that progressed after > l systemic treatments (Tx). Primary objectives were assessment of safety and preliminary efficacy. Results: As of Jan 15, 2025, 170 patients (pts) were enrolled with doses ranging from 0.8 to 2.7mg/kg. 2 out of 6 pts in 2.7mg/kg group had dose limiting toxicity (1 with G3 increased lipase, 1 with G4 thrombocytopenia and G4 febrile neutropenia). The maximum tolerated dose and the RP2D was selected as 2.4mg/kg. 147 pts were enrolled at dose of 2.4mg/kg. The most common TRAEs of 2.4mg/kg dose group (≥20%, all grade/≥5%, ≥G3) were anemia (78.8%,13.7%), white blood cell count decreased (62.3%, 18.5%), nausea (59.6%,0%), stomatitis(59.6%,19.2%), neutrophil count decreased (52.7%,19.2%), platelet count decreased (38.4%,8.2%), vomiting (38.4%,0.7%), lymphocyte count decreased (35.6%,5.5%), fatigue (34.9%, 0%), body weight loss (29.5%, 0.6%), constipation (26.7%,0%), anorexia (23.3%,2.7%). 22 CC pts and 13 EC pts were enrolled at 2.4mg/kg and evaluable for tumor assessment. The obiective response rate (ORR) was 36.4% and 23.1%, respectively. Median prior lines of Tx were 2(range, 1-5). 50% CC and 93% EC pts progressed after platinum-based chemotherapy and immune checkpoint inhibitors, respectively. 23% EC had previously used topoisomerase I inhibitors. Objective responses were also observed in pts with other solid tumor types. Conclusions: The data indicated encouraging efficacy of BAT8008 in advanced CC and EC. The safety profile showed adequate tolerability. Clinical trial information: NCT05620017 . Tumor Type CC EC n 22 13 CR 1 1 PR 7 2 ORR,% 36.4 23.1 cORR,% 31.8 15.4 DCR,% 77.3 100 PFS, months (95% CI) 6.8(3.4-10.2) 5.3(3.1-7.4)