Novel EGFR x HER3 Bispecific Antibody-Drug Conjugate Shows Promise Among Heavily-Pretreated Patients With Advanced Urothelial Carcinoma

BL-B01D1, a first-in-class, novel antibody-drug conjugate that consists of an EGFRxHER3 bispecific antibody linked to a novel TOP-I inhibitor payload, showed encouraging antitumor activity with manageable safety among heavily-treated patients with locally advanced or metastatic urological tumors. 

This trial enrolled 32 patients with advanced urothelial carcinoma with a median of 2 lines of previous systemic treatment. All patients received BL-B01D1 on Day 1 and Day 8 every 3 weeks, with 29 patients receiving 2.2 mg/kg, 2 receiving 2.5 mg/kg, and 3 receiving 2.75 mg/kg.

There were 23 patients who received the 2.2 mg/kg dose who were evaluated for efficacy. The objective response rate was 43.5% and the disease control rate was 91.3% and median progression-free survival was 5.5 months. Among patients who had been treated with 1 line of chemotherapy previously (n = 1), the objective response rate was 90% and the median PFS was not reached. 

The most common treatment-related adverse events (among patients dosed with 2.2 mg/kg), occurring in ≥ 20% of patients, were anemia, leukopenia, thrombocytopenia, neutropenia, nausea, decreased appetite, hypoalbuminemia, vomiting, lymphocyte counte decreased, alopecia, and stomatitis. There were no instances of interstitial lung disease observed. 

The sutyd authors concluded that BL-B01D1 “demonstrated manageable safety with encouraging antitumor activity” among this patient population.  

Source:

Ye D, Bian X, Yang T, et al. BL-B01D1, an EGFR x HER2 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic urothelial carcinoma (UC). Presented at the 2024 ESMO Congress. September 13-17, 2024; Barcelona, Spain.