BL-B01D1 Shows Preliminary Efficacy, Safety in Pretreated Advanced Urothelial Carcinoma

Dingwei Ye, MD

BL-B01D1, an EGFR- and HER3-directed bispecific antibody-drug conjugate (ADC), demonstrated preliminary efficacy and safety in patients with previously treated locally advanced or metastatic urothelial carcinoma, according to findings from the phase 2 BL-B01D1-201 study (NCT05785039) presented at the 2024 ESMO Congress.

Findings showed that in the evaluable patient population treated with the ADC at 2.2 mg/kg (n = 27), patients achieved an overall response rate (ORR) of 40.7% (95% CI, 22.4%-61.2%) and a confirmed ORR of 33.3% (95% CI, 16.5%-54.0%). Best overall responses included partial response (PR; n = 11), confirmed PR (n = 9), stable disease (n = 15), and not evaluable (n = 1). No patients had progressive disease, and the disease control rate (DCR) was 96.3% (95% CI, 81.0%-99.9%).

The median duration of response (DOR) was not reached (NR; 95% CI, NR-NR), and the 6-month DOR rate was 100% (95% CI, 100%-100%). The median progression-free survival (PFS) was NR (95% CI, 4.2-NR), and the 6-month PFS rate was 62.4% (95% CI, 32.2%-82.2%).

“Given the promising results from this trial, plans are underway for registrational studies,” lead study author Dingwei Ye, MD, of the Fudan University Shanghai Cancer Center in China, said during a presentation of the data.

BL-B01D1 represents a potential first-in-class therapeutic option for patients with locally advanced or metastatic urothelial carcinoma, which often has high expressions of both EGFR and HER3.

Eligibility Criteria and Study Design

BL-B01D1-201 included patients with locally advanced or metastatic urothelial carcinoma who had experienced disease progression on standard therapy or had no feasible treatment options. Key inclusion criteria included measurable disease as defined by RECIST 1.1 criteria and an ECOG performance status of 0 or 1.

During the trial, patients were assigned into 3 treatment arms based on dosing: those in cohort 1 (n = 34) received BL-B01D1 at 2.2 mg/kg on day 1 and day 8 every 3 weeks; patients in cohort 2 (n = 4) received BL-B01D1 at 2.5 mg/kg on days 1 and 8 every 3 weeks; and those in cohort 3 (n = 3) were treated with BL-B01D1 at 2.75 mg/kg on day 1 and day 8 every 3 weeks. Treatment continued until disease progression or the development of intolerable toxicity.

The primary end point of the study was ORR by investigator assessment. Secondary end points included DCR, PFS, DOR, and safety.

Patient Characteristics and Additional Efficacy Data

In the overall trial population (n = 41), the median age was 62.0 years (range, 42.0-74.0), and the majority were male (78.0%). Additionally, 41.5% of patients had an ECOG performance status of 0, and 58.5% had a performance status of 1. Primary tumor sites included bladder (53.7%) and upper urinary tract (46.3%). Histologic types included urothelial only (82.9%), urothelial carcinoma with squamous differentiation (12.2%), and urothelial with other components (4.9%). Furthermore, 43.9% of patients received 1 prior line of chemotherapy, and 56.1% received at least 2 prior lines.

Within the 2.2-mg/kg cohort, patients received a median of 2 prior lines of therapy (range, 1-7). In those who received 1 prior line of chemotherapy via platinum-based therapy or an ADC (n = 12), the ORR and confirmed ORR were both 75.0% (95% CI, 42.8%-94.5%). The DCR was 100% (95% CI, 73.5%-100%). The median DOR and PFS were both NR (95% CI, NR-NR), and the 6-month DOR and PFS rates were both 100% (95% CI, 100%-100%).

A biomarker analysis showed that clinical activity in the 2.2-mg/kg cohort was observed across patients with various levels of EGFR and HER3 expression.

Safety Data

Any-grade treatment-related adverse effects (TRAEs) were observed in 100% of patients receiving BL-B01D1 at 2.2 mg/kg (n = 34). Grade 3 or higher TRAEs occurred in 52.9% of patients, and 35.3% experienced serious TRAEs. No treatment-related deaths were reported. TRAEs led to treatment discontinuation and dose reduction in 5.9% and 14.7% of patients, respectively.

The most common any-grade hematologic TRAEs included anemia (82.4%), leukopenia (70.6%), thrombocytopenia (61.8%), neutropenia (55.9%), and decreased lymphocyte count (20.6%). Non-hematologic TRAEs of any grade included decreased appetite (47.1%), nausea (44.1%), hypoalbuminemia (26.5%), vomiting (26.5%), alopecia (23.5%), asthenia (17.6%), constipation (17.6%), diarrhea (17.6%), and stomatitis (17.6%). No cases of interstitial lung disease were observed, and no new safety signals were identified during the study.

Disclosures: Dr Ye reported institutional support from Biokin Pharmaceutical while serving as a steering committee member and trial chair. Dr Ye reported personal compensation while serving on an advisory board for AstraZeneca, Lilly, and Bayer.

Reference

Ye D, Bian X, Yang T, et al. BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic urothelial carcinoma (UC). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Abstract 1959O.