9MW2821, a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open label, multicenter, phase I/II study
Mené sur 274 patients atteints d'une tumeur solide de stade avancé, cet essai multicentrique de phase I/II détermine la dose maximale tolérée de 9MW2821 (un conjugué anticorps-médicament ciblant la nectine-4) puis évalue son efficacité du point de vue du taux de réponse objective
BACKGROUD: A first-in-human study was performed to assess the safety and preliminary antitumor activity of 9MW2821, a next-generation monoclonal antibody-drug conjugate (ADC) that delivers monomethylauristatin E (MMAE) to cells expressing Nectin-4, in patients with advanced solid tumors.
PATIENTS AND METHODS: This is a first-in-human, open label, multicenter study included dose escalation, dose expansion and cohort expansion periods. Patients with advanced solid tumors who failed ≥1 line of systemic therapy were recruited to receive 9MW2821 by intravenous (IV) infusion at doses of 0.33-1.5mg/kg on days 1,8 and 15 of each 28-day cycle. Primary objective were assessment of safety and preliminary efficacy. (NCT05216965, CTR20220106)
RESULTS: Between June 11, 2022, and Apr 3, 2024, 274 patients were enrolled, including 51 with urothelial cancer, 62 with cervical cancer, 49 with esophageal cancer, 20 with triple negative breast cancer and 92 with other solid tumors. In dose escalation phase, one dose limiting toxicity was observed in 1.5mg/kg group, which was grade 4 neutropenia lasted more than 5 days. Maximum tolerated dose of 9MW2821 was not reached. However, the recommended phase
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dose was identified as 1.25mg/kg based on balance of safety and efficacy. The most common ≥Grade 3 treatment related adverse events were neutrophil count decreased, white blood cell (WBC) count decreased, anemia, gamma-glutamyl transferase (GGT) increased rash and peripheral sensory neuropathy in 1.25mg/kg group. Among 226 patients evaluable for efficacy, objective response rates were 54.1%, 32.1%, 14.0% and 50% in urothelial cancer, cervical cancer, esophageal cancer and triple negative breast cancer, respectively.
CONCLUSION: The results suggest that 9MW2821 was tolerable and clinically significant in efficacy in various types of solid tumors besides urothelial cancer. Several pivotal trials are currently in progress. (NCT06196736, NCT06592326, NCT06692166)
Annals of Oncology 2025