Dr Ye on Early Efficacy Data for BL-B01D1 in Metastatic Urothelial Carcinoma

Dingwei Ye, MD, PhD, director of the Multidisciplinary Team for Genitourinary Cancer, director, Fudan University Prostate Cancer Institute, China, discusses the initial efficacy and safety of the potential first-in-class EGFR/HER3-directed antibody-drug conjugate BL-B01D1 in locally advanced or metastatic urothelial carcinoma, as presented in a phase 1b/2 study (NCT05785039) during the 2024 ESMO Congress.

This phase 1b/2 study investigated BL-B01D1 in patients with locally advanced or metastatic urothelial carcinoma who had progressed on standard therapies. The trial tested 3 dose levels (2.2, 2.5, and 2.75 mg/kg) administered every 3 weeks on days 1 and 8 of each cycle, Ye details. Patients continued treatment until progression or unacceptable toxicity.

Among the 27 patients evaluable for efficacy in the 2.2 mg/kg cohort, the confirmed overall response rate (ORR) was 33.3% (95% CI, 16.5%-54.0%), consisting of 11 partial responses (PRs), 9 of which were confirmed, and 15 patients achieving stable disease (SD), Ye reports. One patient was not evaluable. The disease control rate (DCR) reached 96.3% (95% CI, 81.0%-99.9%).

In the subset of 12 patients pretreated with 1 line of chemotherapy, the ORR was 75% (95% CI, 42.8%-94.5%), with 9 confirmed PRs and 3 achieving SD, Ye adds. The DCR for this group was 100% (95% CI, 73.5%-100%). Neither the median progression-free survival nor the median duration of response was reached with BL-B01D1 in either population.

Regarding safety, most adverse effects (AEs) were hematologic and manageable, Ye states. Common treatment-related AEs at the 2.2 mg/kg dose included anemia, leukopenia, thrombocytopenia, neutropenia, nausea, decreased appetite, hypoalbuminemia, vomiting, decreased lymphocyte count, alopecia, and stomatitis. Non-hematologic toxicities were mostly grade 1 or 2, and importantly, no cases of interstitial lung disease were observed. No new safety signals emerged during the study, Ye emphasizes.

These findings suggest that BL-B01D1 has manageable safety and encouraging antitumor activity, particularly in patients who have already been heavily pretreated, Ye concludes. Further evaluation of this promising agent in urothelial cancer is ongoing.