Preliminary Results of 9MW2821 Targeting Nectin-4ADC in Advanced Solid Tumor Patients: Report from ESMO 2023

Introduction:

The preliminary results of the phase I/II study evaluating the safety, tolerability, and preliminary efficacy of 9MW2821, a Nectin-4-targeting antibody-drug conjugate (ADC), in patients with advanced solid tumors were presented by Professor Jian Zhang and the research team from Fudan University Cancer Hospital at the European Society for Medical Oncology (ESMO) Congress held in Madrid, Spain from October 20-24, 2023. Additionally, the results of the phase III study of 8MW0511 were also presented as a poster at the conference.

Background:
Nectin-4 is an adhesive molecule highly expressed in various solid tumors, including urothelial carcinoma. It represents an effective therapeutic target. 9MW2821 is a monoclonal antibody-drug conjugate that delivers MMAE to Nectin-4-expressing cells. This study aimed to assess the safety, tolerability, and preliminary efficacy of 9MW2821 in patients with solid tumors.

Methods:
9MW2821 was administered intravenously on days 1, 8, and 15 of each 28-day cycle. The study included dose escalation, dose expansion, and cohort expansion phases. The cohorts comprised subjects with urothelial carcinoma and other Nectin-4-positive solid tumors. The primary objectives were to evaluate the safety and preliminary efficacy of the drug.

Results:
As of April 27, 2023, a total of 97 patients were enrolled in the study, including 39 with urothelial carcinoma and 29 with cervical cancer. The patients' age ranged from 32 to 78 years, with a median age of 57 years. The dose range administered was 0.33 to 1.5 mg/kg. These subjects had previously received platinum-based chemotherapy and immune checkpoint inhibitors.

No treatment-related deaths were reported in the study. A dose-limiting toxicity of grade 4 neutropenia lasting more than 5 days was observed in only one patient in the 1.5 mg/kg dose group. The maximum tolerated dose had not been reached.

The incidence of any grade treatment-related adverse events in the study was 64.9%. The most common treatment-related adverse events were decreased white blood cell count (36.1%), neutropenia (35.1%), nausea (22.7%), aspartate aminotransferase elevation (22.7%), rash (19.6%), alopecia (19.6%), fatigue (18.6%), decreased appetite (18.6%), anemia (17.5%), vomiting (16.5%), and peripheral sensory neuropathy (16.5%). The incidence of grade 3/4 treatment-related adverse events was 35.1%, with decreased white blood cell count (18.6%) and neutropenia (18.6%) being the most common.

Conclusion:
The preliminary results of the phase I/II study demonstrated that 9MW2821, a Nectin-4-targeting ADC, showed acceptable safety and tolerability profiles in patients with advanced solid tumors. Further evaluation of its efficacy is warranted. These findings provide a basis for future investigations and potential therapeutic applications of 9MW2821 in this patient population.