1959O - BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic urothelial carcinoma (UC)

Background

BL-B01D1 is a potentially first-in-class ADC comprised of an EGFR x HER3 bispecific antibody attached to a novel topoisomerase I inhibitor payload (Ed-04) via a tetrapeptide-based cleavable linker. We now present safety/efficacy data from a phase I study of BL-B01D1 in UC.

Methods

This phase Ib/II study included patients with locally advanced or metastatic urological tumors. The enrolled UC patients were mainly administered at doses of 2.0, 2.5 and 2.75 mg/kg D1D8 Q3W.

Results

As of Apr 29^th, 2024, 32 UC patients were enrolled in Q3W treatment schedule with 29 patients treated at 2.2 mg/kg, 2 patients at 2.5mg/kg and 3 patient at 2.75 mg/kg. The median prior line of systemic treatment was 2 (range, 1-7). Among the enrolled patients, 23 patients dosed at 2.2 mg/kg were evaluable for efficacy, ORR was 43.5% (10/23), cORR was 34.8% (8/23), DCR was 91.3% (21/23), mPFS was 5.5 months. For patients pretreated with one chemotherapy line, ORR was 90% (9/10), cORR was 80% (8/10), mPFS was not reached. The most common TRAEs at 2.2mg/kg (≥20%, all Grade /≥G3) were anemia (74%/17%), leukopenia (65%/26%), thrombocytopenia (65%/26%), neutropenia (44%/22%), nausea (39%/0%), decreased appetite (30%/4%), hypoalbuminemia (30%/0%), vomiting (30%/0%), lymphocyte count decreased (22%/4%), alopecia (22%/0%), and stomatitis (22%/0%). No interstitial lung disease (ILD) was observed. No new safety signals were observed.

Conclusions

In patients with heavily pretreated UC, BL-B01D1 demonstrated manageable safety with encouraging antitumor activity. Further evaluation of BL-B01D1 in this patient population is ongoing.

Clinical trial identification

NCT05785039.

Editorial acknowledgement

Legal entity responsible for the study

Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Funding

Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.

Disclosure

S. Xiao: Financial Interests, Personal, Full or part-time Employment: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.; Financial Interests, Personal, Stocks/Shares: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.. H. Wang: Financial Interests, Personal, Full or part-time Employment: Systimmune Inc. H. Zhu: Financial Interests, Personal, Full or part-time Employment: SystImmune Inc; Financial Interests, Personal, Stocks/Shares: SystImmune Inc. Y. Zhu: Financial Interests, Personal, Full or part-time Employment: SystImmune Inc; Financial Interests, Personal, Ownership Interest: SystImmune Inc, Baili Pharmaceutical. All other authors have declared no conflicts of interest.