54P - BL-B01D1, an EGFR x HER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic biliary tract carcinoma (BTC)

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 BTC.

Methods

This phase I study included patients with locally advanced or metastatic gastrointestinal cancers. In the dose-expansion phase, the enrolled BTC patients were mainly administered at doses of 2.5, 3.0 and 3.5 mg/kg D1D8 Q3W.

Results

As of Apr 29^th, 2024, 39 BTC patients were enrolled in Q3W treatment schedule with 27 patients treated at 2.5 mg/kg, 3 patients at 3.0 mg/kg and 9 patients at 3.5 mg/kg*. The median prior line of systemic treatment was 2 (range, 1-4). Among the enrolled patients, 21 patients dosed at 2.5mg/kg were evaluable for efficacy, ORR was 28.6% (6/21), cORR was 23.8% (5/21), DCR was 76.2% (16/21). The antitumor activity in intrahepatic and extrahepatic cholangiocarcinoma had no obvious difference. Among 4 gallbladder cancer patients, 2 of them showed response (1 cCR, 1cPR). The most common TRAEs at 2.5mg/kg (all Grade /≥G3) were anemia (67%/10%), thrombocytopenia (62%/24%), leukopenia (48%/14%), nausea (48%/0%), asthenia (33%/10%), lymphocyte count decreased (29%/0%), blood alkaline phosphatase increased (24%/5%), neutropenia (19%/5%), dizziness (19%/5%), alopecia (19%/0%), and stomatitis (19%/0%). No interstitial lung disease (ILD) was observed. No new safety signals were observed. Note: * excluded one prior treatment naïve patient in 3.5 mg/kg.

Conclusions

In patients with locally advanced or metastatic BTC, BL-B01D1 demonstrated manageable safety with encouraging antitumor activity. Further evaluation of BL-B01D1 in this patient population is ongoing.

Clinical trial identification

NCT05262491.

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-Bio Pharmaceutical. L. Shen: Financial Interests, Personal, Advisory Board: MSD, BI, Servier, AZ, Transcenta Holding Limited; Financial Interests, Institutional, Funding: BeiGene, Ltd.; Financial Interests, Institutional, Trial Chair: Rongchang Pharmaceutical, Roche, Innovent, BeiGene, Ltd., NovaRock Biotherapeutics Limited. All other authors have declared no conflicts of interest.