A first-in-human clinical study of 9MW2921, a novel TROP-2 antibody-drug conjugate (ADC), in patients with advanced solid tumors.

3029 Background: TROP-2 (trophoblast cell surface antigen 2) is commonly overexpressed in multiple solid tumors and associated with poor prognosis. 9MW2921 is a novel TROP-2 ADC developed with a site-specific linker to conjugate the class of novel camptothecin-based payload Mtoxin, with a drug-to-antibody-ratio (DAR) of 4. Here we report the safety and efficacy data of 9MW2921 in patients with advanced solid tumors in a phase 1 study. Methods: 9MW2921 was administered by intravenous infusion at doses of 1.0-6.0 mg/kg once every 3 weeks. Primary objectives were assessment of dose-limiting toxicity, safety and the recommended phase 2 dose/maximum dose. Results: As of 12 November, 2024, thirty-nine patients (pts) were enrolled and treated at dose levels of 1.0 (N = 1), 2.0 (N = 3), 2.5 (N = 12), 3.0 (N = 20) and 4.5 (N = 3) mg/kg. The average age of all patients was 55.6 (range: 37-72) years with 20.5% male and 79.5% female. The median prior therapy lines were 2 (range: 1~11); 48.7% pts treated after immunotherapy. Three patients at 4.5mg/kg experienced at least one dose limiting toxicity (DLT), and this dose level was considered intolerable. No other pts was observed DLTs at the 1.0~3.0 mg/kg groups. The most common ≥grade 3 (≥5% pts)TRAEs were stomatitis, anemia, white blood cell (WBC) count decreased, neutropenia, lymphocyte count decreased, rash, vomiting and platelet count decreased. There were no TRAEs leading to death. 38 pts were evaluable for efficacy with at least one post-baseline tumor assessment, 12 pts achieved partial response and 16 pts maintained stable disease. The ORR of 3.0 mg/kg was 42.1% (8/19) and DCR was 84.2% (16/19). The ORR, DCR of 3.0 mg/kg in patients diagnosed with endometrial cancer (4 pts), HR+/HER2- breast cancer (4 pts), HER2- gastric cancer (4 pts) and Non-squamous non-small cell lung cancer (4 pts) were 75%, 100%; 50%, 75%; 50%, 100%; 25%, 100%, respectively. Conclusions: The data indicated that 9MW2921 has acceptable tolerability and promising anti-tumor activity in patients with advanced EC, HR+/HER2- BC, HER2- GC and nsq-NSCLC. Clinical trial information: NCT05990452 .