New data presented at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain, indicates that BL-B01D1, an epidermal growth factor receptor (EGFR) / epidermal growth factor 3 (HER3) bispecific antibody-drug conjugate, may offer a promising treatment option for patients with previously treated urothelial carcinoma. The Phase 2 trial results demonstrate preliminary efficacy and a tolerable safety profile at a 2.2 mg/kg dose administered once every three weeks.
Phase 2 Trial Results
The study, led by Dingwei Ye from Fudan University Shanghai Cancer Center, evaluated the safety, tolerability, and preliminary efficacy of BL-B01D1 in patients with locally advanced or metastatic urothelial carcinoma who had progressed on or were ineligible for standard therapies. The investigational drug combines a bispecific antibody with a novel topoisomerase I inhibitor.
"EGFR and HER3 are highly expressed in urothelial carcinoma," the investigators noted. "Targeting EGFR and HER3 could provide a promising therapeutic option for urothelial carcinoma."
The trial assessed doses of 2.2, 2.5, and 2.75 mg/kg of BL-B01D1, administered every three weeks. Key eligibility criteria included an ECOG performance status of 0 or 1, measurable disease, and failure of standard therapy or lack of feasible treatment options. Treatment continued until disease progression or unacceptable toxicity.
The primary endpoint was overall response rate (ORR) per investigator assessment. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and duration of response (DOR), as well as safety and tolerability.
Efficacy Outcomes
Of the 41 patients enrolled, 34 received the 2.2 mg/kg dose. The median patient age was 62 years, with 78% being male and 58.5% having a baseline ECOG-PS score of 1. A majority (56.1%) had previously received two or more lines of chemotherapy.
At the 2.2 mg/kg dose, the ORR was 40.7% (95% CI, 22.4 – 61.2). Notably, in the subgroup of 12 patients who had received only one prior line of chemotherapy, the ORR improved to 75.0% (95% CI, 42.8 – 94.5). The six-month DOR rate was 100% for all patients receiving the 2.2 mg/kg dose, and the six-month PFS rate was 62.4% (95% CI, 32.2 – 82.2), increasing to 100% in patients with one prior line of chemotherapy.
"Also, in the patients with 1 prior line of chemotherapy at a 2.2 (mg/kg dose), they have a favorable duration," Dr. Ye stated at ESMO. "The longest duration of the treatment is more than 11 months. Also, all the patients in these subgroups have (achieved) tumor shrinkage."
Safety Profile
Over a median follow-up of 4.6 months in the 2.2 mg/kg arm, treatment-related adverse events (TRAEs) led to dose reduction in 5 patients and discontinuation in 2. The most common TRAEs included hematological toxicities such as anemia, leukopenia, and thrombocytopenia, as well as decreased appetite and nausea. No new safety signals were identified.
Implications and Future Directions
The investigators concluded that BL-B01D1 demonstrated encouraging preliminary efficacy and a favorable safety profile at the 2.2 mg/kg dose every three weeks in previously treated urothelial carcinoma patients. Clinical activity was observed across various levels of EGFR and HER3 expression, according to biomarker analyses.
SystImmune, the company developing BL-B01D1, intends to advance the therapy through clinical assessment as both a monotherapy and in combination regimens for various cancer patients.
"These data support our continued conviction that BL-B01D1 has a manageable safety profile and add to the body of evidence that shows encouraging signals of efficacy across a wide variety of tumors," said Jonathan Cheng, MD, chief medical officer of SystImmune. "This positions BL-B01D1 as a versatile therapeutic option that may address the unmet medical needs of patients with limited treatment options."
