1426P - BL-B01D1, an EGFR x her3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC)

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 ESCC.

Methods

This phase I study included patients with locally advanced or metastatic gastrointestinal cancers. In the dose-expansion phase, the enrolled ESCC patients were mainly administered at doses of 2.0, 2.5 and 3.0 mg/kg D1D8 Q3W.

Results

As of Jan 31^st, 2024, 83 previously treated ESCC patients were enrolled in Q3W treatment schedule with 22 patients treated at 2.0 mg/kg, 60 patients at 2.5mg/kg and 1 patient at 3.0mg/kg. Among the enrolled ESCC patients, 94.0% (78/83) had received anti-PD-1/L1 and platinum-based chemotherapy in combination or sequentially. The median prior line of systemic treatment was 2 (range, 1-7) and the median follow-up for OS was 6.3 months. Among the enrolled patients, 74 patients were evaluable for efficacy. The ORR was 33.8% (25/74), cORR was 29.7% (22/74), DCR was 70.3% (52/74), mDOR was not reached, mPFS was 4.1 months, mOS was 6.6 months, 6 months survival rate was 57.5%. For patients dosed at 2.5 mg/kg (RP2D), ORR was 42.3% (22/52), cORR was 36.5% (19/52), DCR was 80.8% (42/52), mDOR was not reached, mPFS was 5.0 months, mOS was not reach, 6 months survival rate was 64.5%. The incidence of ≥ G3 TRAEs at 2.5 mg/kg was 53%, and the most common ≥G3 TRAEs were anemia (25%), leukopenia (18%), thrombocytopenia (18%), neutropenia (15%), lymphocyte count decreased (15%), etc. One G3 interstitial lung disease (ILD) by investigator's adjudication was observed. No new safety signals were observed.

Conclusions

In patients with heavily pretreated ESCC, 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 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.