Data from the phase 2 BL-B01D1-201 trial indicate that izalontamab brengitecan (also known as BL-B01D1) demonstrates significant efficacy in treating patients with locally advanced or metastatic urothelial carcinoma. The trial, which involved 34 patients, reported a confirmed objective response rate (ORR) of 44.1% and a disease control rate (DCR) of 88.2%, as published in the Journal of Clinical Oncology.
Lead study author Xiaojie Bian, MD, PhD, from the Fudan University Shanghai Cancer Center, emphasized the potential of izalontamab brengitecan, stating, “These results suggest that BL-B01D1 could be a promising new agent for patients with locally advanced or metastatic urothelial carcinoma with few treatment options.” The trial results were first presented at the 2024 ESMO Congress.
Details of the Trial and Efficacy Outcomes
The BL-B01D1-201 trial was a multicenter, single-arm study designed to assess the activity of izalontamab brengitecan in patients whose disease had progressed after standard therapies. To qualify for the study, participants had to be aged between 18 and 75, exhibit disease progression post-treatment, and maintain adequate organ function.
Patients received doses of 2.2, 2.5, and 2.75 mg/kg of izalontamab brengitecan intravenously over approximately 60 minutes on days 1 and 8 of each three-week cycle. The primary endpoint of the trial was ORR, with secondary endpoints including progression-free survival (PFS) and duration of response (DOR).
Among the 34 patients treated with 2.2 mg/kg, the best ORR was 50%, with 17 patients achieving partial responses. The median PFS was reported at 7.3 months, and the median overall survival (OS) was 12.3 months. These results underscore the potential of izalontamab brengitecan in a patient population with limited treatment options.
Safety Profile and Future Implications
While the initial dose for the trial was set at 2.75 mg/kg, patients experienced grade 3 or higher treatment-related adverse effects (TRAEs), prompting a reduction to 2.2 mg/kg. Among those receiving this dose, every patient experienced at least one TRAE, although no treatment-related deaths occurred. The most frequently reported hematologic TRAEs included anemia and leukopenia, affecting 88.2% and 76.5% of patients, respectively.
The findings from the trial hold promise, particularly as they represent the first phase 2 study of an EGFR/HER3-targeting ADC in this patient demographic. The results may pave the way for new treatment options in urothelial carcinoma, where prognosis remains poor with conventional therapies.
Future studies will be critical in expanding the understanding and application of izalontamab brengitecan, particularly in combination therapies. For instance, a phase 2 trial is currently exploring its use with osimertinib in the first-line treatment of patients with EGFR-mutated lung cancer.
As the landscape of cancer treatment continues to evolve, the promising results from the BL-B01D1-201 trial could significantly impact how advanced urothelial carcinoma is managed globally.