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Bulumtatug Fuvedotin (BFv, 9MW2821), a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with
1Phase I Unit, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Background:
A first-in-human study was carried out to assess the safety and preliminary antitumor activity of bulumtatug fuvedotin (BFv; 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 was a first-in-human, open-label, multicenter study and included dose escalation, dose expansion and cohort expansion periods. Patients with advanced solid tumors who failed one or more lines of systemic therapy were recruited to receive BFv by intravenous (IV) infusion at doses of 0.33-1.5 mg/kg on days 1, 8 and 15 of each 28-day cycle. Primary objective was assessment of safety and preliminary efficacy. (NCT05216965, CTR20220106).
Results:
Between 11 June 2022 and 3 Apr 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 the dose escalation phase, one dose-limiting toxicity was observed in the 1.5 mg/kg group, which was grade 4 neutropenia that lasted >5 days. Maximum tolerated dose of BFv was not reached. However, the recommended phase II dose was identified as 1.25 mg/kg based on a balance of safety and efficacy. The most common grade ≥3 treatment-related adverse events were decreased neutrophil count, decreased white blood cell count, anemia, increased gamma-glutamyl transferase (GGT) with rash, and peripheral sensory neuropathy in the 1.25 mg/kg group. Among 221 patients assessable for efficacy in 1.25 mg/kg group, 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.
Conclusions:
The results suggest that BFv 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).
Insights
The novel monoclonal antibody-drug conjugate 9MW2821 shows promising safety and efficacy in advanced solid tumors, including urothelial and triple-negative breast cancer. Further pivotal trials are underway to confirm these significant findings.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- A first-in-human study evaluated 9MW2821, a novel monoclonal antibody-drug conjugate (ADC) targeting Nectin-4 with monomethylauristatin E (MMAE).
- The study focused on patients with advanced solid tumors who had previously undergone systemic therapy.
Purpose of the Study:
- To assess the safety profile of 9MW2821 in patients with advanced solid tumors.
- To evaluate the preliminary antitumor activity and determine the recommended Phase II dose of 9MW2821.
Main Methods:
- A first-in-human, open-label, multicenter study involving dose escalation and expansion cohorts.
- Patients received 9MW2821 intravenously at doses ranging from 0.33-1.5 mg/kg across 28-day cycles.
- Safety and efficacy were primary endpoints, with enrollment from June 2022 to April 2024.
Main Results:
- The recommended Phase II dose was determined to be 1.25 mg/kg, balancing safety and efficacy.
- Common Grade 3 treatment-related adverse events included decreased neutrophil and white blood cell counts, anemia, rash, and peripheral neuropathy.
- Objective response rates were 54.1% in urothelial cancer, 32.1% in cervical cancer, 14.0% in esophageal cancer, and 50% in triple-negative breast cancer.
Conclusions:
- 9MW2821 demonstrated tolerability and clinically significant efficacy across various solid tumors beyond urothelial cancer.
- Ongoing pivotal trials are investigating the therapeutic potential of 9MW2821 in different cancer types.
