659MO Preliminary results from a phase I/II study of 9MW2821, an antibody-drug conjugate targeting nectin-4, in patients with advanced solid tumors

Nectin-4 is an adhesion molecule that highly expressed in variety of solid tumors and could be a potent therapeutic target. 9MW2821 is a monoclonal antibody-drug conjugate (ADC) that delivers monomethyl auristatin E to cells expressing Nectin-4. Here we report the first-in-human, multicenter, phase I/II study designed to explore the safety, pharmacokinetics and efficacy of 9MW2821 in advanced solid tumors. 9MW2821 was administered by intravenous infusion on days 1, 8 and 15 of each 28-day cycle. The study included dose escalation, dose expansion and cohort expansion period which included urothelial cancer (UC) and other Nectin-4 positive solid tumors. Primary objectives were assessment of safety and preliminary efficacy. As of April 27, 2023, 97 patients (pts) were enrolled with doses ranging from 0.33 to 1.5mg/kg. Median age was 57 years (range, 32-78). Only 1 dose limiting toxicity of grade 4 neutropenia lasted more than 5 days was observed at 1.5mg/kg group. Maximum tolerated dose was not yet reached. Treatment related adverse events (TRAEs) of any grade occurred in 64.9% pts. The most common TRAEs were white blood cell (WBC) count decreased (36.1%), neutropenia (35.1%), nausea (22.7%), aspartate aminotransferase increased (22.7%), rash (19.6%), alopecia (19.6%), fatigue (18.6%), decreased appetite (18.6%), anemia (17.5%), vomiting (16.5%), peripheral sensory neuropathy (16.5%). Grade 3/4 TRAEs occurred in 35.1% pts. The most common grade 3/4 TRAEs were WBC count decreased (18.6%) and neutropenia (18.6%). Treatment related death was not observed. Among 39 pts treated with 9MW2821 at 1.25mg/kg or above and evaluable for tumor assessment, objective response rate (ORR) and disease control rate (DCR) was 38.5% and 84.6%, respectively. In 18 pts with UC who progressed after platinum-based chemotherapy and immune checkpoint inhibitors and dosed at 1.25mg/kg, ORR and DCR was 55.6% and 94.4%, respectively. Objective responses were also observed in pts with breast cancer and cervical cancer. The results showed that 9MW2821 had manageable safety profile and promising antitumor activity. Enrollment continues to determine efficacy of 9MW2821 in certain solid tumors.