Mabwell (688062.SH), an innovation-driven biopharmaceutical company, announced the data and latest progress of the Phase I/II clinical study of 9MW2821, a novel Nectin-4-targeting ADC for multiple advanced solid tumors, which will be reported as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

As of April 1, 2024, among 240 patients in the 1.25 mg/kg dose group in the Phase II clinical trial:

>> Urothelial Carcinoma (UC)

Of the 37 patients evaluable for efficacy assessment, the objective response rate (ORR) and disease control rate (DCR) were 62.2% and 91.9%, respectively, with median progression-free survival (mPFS) was 8.8 months and median overall survival (mOS) was 14.2 months.

>> Cervical Cancer (CC)

Of the 53 patients evaluable for efficacy assessment, 51% were previously treated with platinum-based doublet chemotherapy and bevacizumab, and 58% received platinum-based doublet chemotherapy and immune checkpoint inhibitor, with ORR and DCR were 35.8% and 81.1%, respectively. The mPFS was 3.9 months, with mOS not reached. Of the patients with Nectin-4 tumor cell staining intensity 3+, the ORR was 43.6% among the 39 evaluable patients.

>> Esophageal Cancer (EC)

Of the 39 patients evaluable for efficacy assessment, ORR and DCR were 23.1% and 69.2%, respectively, with mPFS of 3.9 months and mOS of 8.2 months; 37 of them were treated with platinum-based chemotherapy and immunotherapy previously.

>> Triple-negative Breast Cancer (TNBC)

Of the 20 patients with locally advanced or metastatic triple-negative breast cancer and evaluable for efficacy assessment, the ORR and DCR were 50.0% and 80.0% respectively. The mPFS was 5.9 months, and the mOS was not yet reached, with one patient achieved complete response (CR) and had been in CR for 20 months and is currently sustained to be CR. 

>> Safety Profile

To date, the most common treatment-related adverse events (all grade, ≥grade 3) in the 240 patients in the 1.25 mg/kg dose group were white blood cell count decreased (50.8%, 23.3%), neutrophil count decreased (46.3%, 27.9%), anemia (43.8%, 8.3%), aspartate aminotransferase increased (42.1%, 2.9%), alanine aminotransferase increased (35.4%, 2.1%), asthenia (32.1%, 2.9%), rash (30.0%, 5.0%), decreased appetite (28.8%, 1.3%), nausea (26.7%, 0%), hyperglycemia (25.4%, 2.1%), platelet count decreased (24.2%, 4.6%), alopecia (24.2%, 0%), hypoaesthesia (22.5%, 1.7%), constipation (21.3%, 0%), vomiting (20.9%, 1.3%), hypertriglyceridemia (20.4%, 2.1%), and gamma glutamyl aminotransferase increased (15.8%, 5.4%). The data suggest that 9MW2821 has a manageable safety profile.

About 9MW2821

9MW2821 is the first site-specific conjugated novel Nectin-4-targeting ADC developed by Mabwell using ADC platform and automated high-throughput hybridoma antibody molecular discovery platform, and is the first drug candidate to enter clinical study among the Nectin-4-targeting ADCs developed by Chinese companies, and the first therapeutic drug candidate targeting Nectin-4 in the world to reveal clinical efficacy data of cervical cancer, esophageal cancer and breast cancer. 9MW2821 has been granted Fast Track Designation (FTD) for the treatment of advanced, recurrent, or metastatic esophageal squamous cell carcinoma in Feb. 2024, and also respectively granted Orphan Drug Designation (ODD) and FTD for the treatment of esophageal cancer and recurrent or metastatic cervical cancer progressed on or following prior treatment with a platinum-based chemotherapy regimen in May 2024.

9MW2821 achieves site-specific modification of antibody through proprietary conjugate technology linkers and optimized ADC conjugation process. After injection, 9MW2821 can specifically bind to Nectin-4 on the cell membrane surface, be internalized and release cytotoxic drug, and induce the apoptosis of tumor cells.