BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate (ADC), in patients with locally advanced or metastatic solid tumor: Results from a first-in-human phase 1 study.
Li Zhang, Yuxiang Ma, Yuanyuan Zhao, Wenfeng Fang, Hongyun Zhao, Yan Huang, Yunpeng Yang, Likun Chen, Xue Hou, Wen Zou, Muran Ding, Jing Yu, Suoyu Zhang, Jun‐Xian Wang, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Olivo, Yi Zhu
Abstract
3001 Background: BL-B01D1 is a first-in-class novel ADC consisting of an EGFRxHER3 bispecific antibody linked to a novel TOP-I inhibitor payload via a cleavable linker. We now present safety/efficacy results from a FIH phase I study of BL-B01D1. Methods: This study included patients (pts) with locally advanced or metastatic solid tumors. For dose escalation (D-ESC, i3+3), BL-B01D1 was administered intravenously at doses of 0.27, 1.5, 3.0 mg/kg QW, 2.5, 3.0, 3.5mg/kg D1D8 Q3W or 4.5, 5.0, 6.0 mg/kg D1 Q3W. A subset of pts were enrolled into dose-expansion (D-EXP) at Q3W regimens. Results: As of Dec 31, 2022, 150 pts were enrolled and received at least one dose (D-ESC, n=25; D-EXP, n=125). DLTs were neutropenia, febrile neutropenia and thrombocytopenia at 3.0mg/kg QW and 3.5mg/kg D1D8 Q3W. The MTDs were determined to be 3.0mg/kg D1D8 Q3W and 6.0mg/kg D1 Q3W. D-EXP was carried out at 2.5, 3.0mg/kg D1D8 Q3W and 4.5, 5.0, 6.0 mg/kg D1 Q3W. 144 pts were enrolled across all Q3W dose levels (D-ESC and D-EXP), including 89 NSCLC, 7 SCLC, 27 nasopharyngeal cancer (NPC), 19 HNSCC and 2 others. Most common TRAEs (>10%, all grade / ≥ G3) were leukopenia (60%/30%), neutropenia (51%/34%), anemia (45%/15%), thrombocytopenia (44%/19%), alopecia (30%/0%), nausea (29%/<1%), vomiting (28%/0%), asthenia (21%/<1%), decreased appetite (22%/<1%), asthenia (21%/<1%), hypophagia (16%/0%), diarrhoea (15%/2%), mouth ulceration (15%/<1%), rash (13%/0%). No ILD was observed. 122 pts were evaluable for efficacy (at least 1 tumor assessment). PK and other details will be updated in the meeting. Conclusions: BL-B01D1 demonstrated encouraging efficacy in heavily pretreated metastatic/locally advanced solid tumors, especially in pts with EGFRm NSCLC. The safety profile showed adequate safety and tolerability. Clinical trial information: NCT05194982 . [Table: see text]