BL-B01D1 shows favorable phase 2 efficacy, safety for urothelial carcinoma

Epidermal growth factor receptor (EGFR) / epidermal growth factor 3 (HER3) bispecific antibody-drug conjugate BL-B01D1 may be a promising investigative therapy for patients with previously treated urothelial carcinoma, according to new data presented at the European Society for Medical Oncology (ESMO) 2024 Congress in Barcelona, Spain, this week.¹

A team of China-based investigators presented new findings from a phase 2 trial showing the potential first-in-class antibody-drug conjugate BL-B01D1 provided preliminary efficacy and a tolerable safety profile at a 2.2 mg /kg dose administered once every 3 weeks.

Led by Dingwei Ye, a urinary surgery specialist at Fudan University Shanghai Cancer Center in China, investigators sought to observed safety, tolerability and preliminary efficacy outcomes in patients with previously treated urothelial carcinoma who received BL-B01D1 in the phase 2 trial. As they noted, the investigative drug has high clinical potential given its bispecific antibody bound to a novel topoisomerase I inhibitor.

“EGFR and HER3 are highly expressed in urothelial carcinoma,” investigators wrote. “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 BL-B01D1, administered once weekly in patients with locally advanced or metastatic urothelial carcinoma. Eligible patients had low ECOG scores of 0 or 1 at baseline, with measurable disease and a history of failure with standard therapy or being without feasible treatment. Investigative treatment was administered to patients until disease progression or intolerable toxicity was observed.

Ye and colleagues sought a primary endpoint of overall response rate (ORR) per investigator’s assessment. Key secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and duration of response (DOR). The team additionally sought safety and tolerability outcomes in treated patients.

Among the 41 total trial participants, 34 received a 2.2 mg/kg dose; 4 received a 2.5 mg/kg dose, and 3 received a 2.75 mg/kg dose. Median patient age was 62.0 years old; 32 (78%) participants were male and 24 (58.5%) reported a baseline ECOF-PS score of 1. A majority (n = 33 [56.1%]) of patients previously received ≥2 lines of chemotherapy.

Focusing specifically on the 2.2 mg/kg dose of BL-B01D1, investigators observed an ORR of 40.7% (95% CI, 22.4 – 61.2), a rate that which improved to 75.0% among the 12 patients to receive 1 prior line of chemotherapy (95% CI, 42.8 – 94.5). Six-month DOR rates were 100% for all patients receiving 2.2 mg/kg BL-B01D1; 6-month PFS rates were 62.4% (95% CI, 32.2 – 82.2). However, the rate improved to 100% among patients with 1 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,” Ye said in his presentation at ESMO. “The longest duration of the treatment is more than 11 months. Also, all the patients in these subgroups have (achieved) tumor shrinkage.”

Regarding treatment-related adverse events (TRAEs), investigators observed 5 TRAEs leading to dose reduction and 2 leading to discontinuation over the 4.6 median months of follow-up with the 2.2 mg/kg arm. The most common TRAEs in the arm included hematological toxicities like anemia, leukopenia and thrombocytopenia, as well as effects like decreased appetite and nausea. Investigators noted no new safety signals with the therapies.

Investigators concluded BL-B01D1 provided “encouraging” preliminary efficacy outcomes as well as a favorable safety profile at the observed 2.2 mg/kg dose administered every 3 weeks to patients with previously treated urothelial carcinoma. They additionally observed clinical activity across various levels of EGFR and HER3 expression with the bispecific antibody-drug conjugate, per biomarker analyses.

In a statement accompanying the ESMO data readout, BL-B01D1 developing company SystImmune expressed their intent to advance the therapy through clinical assessment as both a combination and therapy options for various patients with cancer.²

“These data support our continued conviction that BL-B01D1has 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, said in the statement. “This positionsBL-B01D1 as a versatile therapeutic option that may address the unmet medical needs of patients with limited treatment options.”

References

1. ^{Ye D, Bian X, Yang T, Cao M, et al. BL-B01D1, an EGFR x HER3 Bispecific Antibody-drug Conjugate (ADC), in Patients with Locally Advanced or Metastatic Urothelial Carcinoma (UC). Poster presented: ESMO Congress 2024. Barcelona, Spain. September 13 – 17, 2024.}
2. ^{Systimmune. SystImmune, Inc. to Present New BL-B01D1 Data in Urothelial, Biliary Tract, and Esophageal Squamous Cell Carcinoma at ESMO Congress 2024. Press release. Published September 9, 2024. Accessed September 13, 2024. https://systimmune.com/news---systimmune-inc-to-present-new-bl-b01d1-data-in-urothelial-biliary-tract-and-esophageal-squamous-cell-carcinoma-at-esmo-congress-2024}