Efficacy and Safety of BL-B01D1 in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: A Phase II Clinical Trial
Xiaojie Bian, Tiejun Yang, Yin Huaqi, Bin Hu, Kai Yao, Shusuan Jiang, Yu Chen, Jing Lin, Manming Cao, Nan Liu, Bin Fu, Changlu Hu, Zhongquan Sun, Qin Yang, Xiaolin Wang, Zhixian Yu, Qingyun Zhang, Xuepei Zhang, Yi Zhu, Hai Zhu, Sa Xiao, Dingwei Ye
Abstract
PURPOSE: To evaluate the efficacy and safety of BL-B01D1, a potential first-in-class epidermal growth factor receptor (EGFR)-human EGFR 3 bispecific antibody-drug conjugated (ADC) with Ed-04, in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) refractory to standard or regular therapies. METHODS: BL-B01D1-201 is a multicenter, single-arm, phase II study of BL-B01D1 in patients with la/mUC who have progressed on systemic therapy. Patients received BL-B01D1 at a dose of 2.2, 2.5, or 2.75 mg/kg intravenously over approximately 60 minutes on days 1 and 8 once every 3 weeks. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), duration of response (DOR), and safety. RESULTS: A total of 41 patients were enrolled, 34 in 2.2 mg/kg, four in 2.5 mg/kg, and three in the 2.75 mg/kg group. In the 2.2 mg/kg group, the confirmed ORR was 44.1% (95% CI, 27.2 to 62.1) and the DCR was 88.2% (95% CI, 72.5 to 96.7). Among 15 patients who had received only one previous line of chemotherapy (either platinum-based or ADCs), the confirmed ORR achieved 80% (95% CI, 51.9 to 95.7). With a median follow-up of 10.2 months, the median PFS was 7.3 months (95% CI, 5.5 to 9.8) and the median DOR was 11.3 months (95% CI, 4.3 to not reached). The most common treatment-related adverse events (all grade/≥grade 3) were anemia (88.2%/38.2%), leukopenia (76.5%/38.2%), neutropenia (64.7%/41.2%), thrombocytopenia (64.7%/32.4%), appetite decrease (52.9%/2.9%), and nausea (52.9%/2.9%). CONCLUSION: BL-B01D1 showed promising preliminary efficacy and a favorable safety profile at 2.2 mg/kg in patients with la/mUC who had progressed after systemic therapy. These results suggest that BL-B01D1 could be a promising new agent for patients with la/mUC with few treatment options.