1316MO - BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with non-small cell lung cancer: Updated results from first-in-human phase I study

Background

BL-B01D1 is a first-in-class novel antibody drug conjugate (ADC) consisting of an EGFRxHER3 bispecific antibody bounded to a novel TOP-I inhibitor payload via a cleavable linker. We now report updated safety/efficacy results from the NSCLC patients (pts) of the BL-B01D1 phase I study.

Methods

This study enrolled pts with locally advanced or metastatic NSCLC and tested doses of 2.5, 3.0, and 3.5 mg/kg administered on D1D8Q3W, as well as doses of 5.0 and 6.0 mg/kg administered on D1Q3W.

Results

As of Mar 31^st, 2023, 114 NSCLC pts who failed standard treatment were enrolled and received at least one dose of BL-B01D1. The most common TRAEs (>10%, all grade/≥ G3) were anemia (59%/25%), leukopenia (59%/28%), neutropenia (51%/32%), thrombocytopenia (48%/23%), nausea (36%/<1%), vomiting (34%/2%), alopecia (27%/0%), decreased appetite (24%/<1%), asthenia (23%/0%), mouth ulceration (21%/0%), diarrhea (20%/<1%), hypophagia (19%/0%), hypokalemia (15%/0%), hypoalbuminemia (12%/0%), rash (11%/0%). No ILD was observed. 88 pts were evaluable for efficacy (at least 1 post-baseline tumor assessment), mPFS for EGFRmut and EGFRwt NSCLC was 6.9 (4.3, ∼) and 5.2 (3.9, ∼) months, respectively, although these results are still considered immature. The study is currently ongoing and further updates regarding DoR, mPFS, and other results will be provided during the meeting. Table: 1316MO

¹All had prior EGFR TKI, 89% (34/38) had prior 3^rd-generation EGFR TKI and 74% (28/38) had prior platinum-based chemotherapy (PBC). ²All had prior PBC, 90% (45/50) had prior anti-PD-1/L1 and PBC. ³During 12/2022∼01/2023, 9 pts (4 EGFRmut, 5 EGFRwt) had skipped at least 25% of the planned doses due to COVID-19 during 1^st and 2^nd tumor assessments.

Conclusions

BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced NSCLC, especially in pts with EGFRmut. The observed toxicity is deemed acceptable.

Clinical trial identification

NCT05194982.

Editorial acknowledgement

Legal entity responsible for the study

Sichuan Baili Pharmaceutical Co., Ltd.

Funding

Sichuan Baili Pharmaceutical Co., Ltd.

Disclosure

L. Zhang: Financial Interests, Institutional, Research Grant, research grant & Trial Chair: AZ; Financial Interests, Institutional, Research Grant: BMS, Roche; Financial Interests, Institutional, Trial Chair: QiLu pharm, Henrui Pharm, Novartis, Hansoh Pharma, China Shiyao Pharma, Kelun Pharm. J. Wang: Financial Interests, Personal, Full or part-time Employment: Baili-Bio Pharmaceutical Co. Ltd. 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. M.S. Olivo: Financial Interests, Institutional, Officer, I'm the CMO of the company: SystImmune; Financial Interests, Institutional, Stocks/Shares: SystImmune. 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.