Abstract PS08-07: BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with Locally Advanced or Metastatic Breast Cancer and other Solid Tumor: Results from a phase 1 study

Abstract 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 present safety/efficacy data from a phase I study of BL-B01D1 in breast cancer. Methods: This study included patients (pts) with locally advanced or metastatic breast cancer (BC) and other solid tumors. BL-B01D1 was administered intravenously at doses of 2.5mg/kg Day 1 & Day 8 every 3 weeks (D1D8Q3W) or 5.0mg/kg Day 1 every 3 weeks (D1Q3W) during dose escalation (D-ESC, i3+3) based on the information obtained during the first-in-human study in solid tumors. A subset of pts will be enrolled in the dose-expansion (D-EXP) phase. Results: As of June 26, 2023, 42 pts were enrolled and received at least one dose (D-ESC, n=8; D-EXP, n=34) of BL-B01D1. Only one DLT of febrile neutropenia was observed at 5.0mg/kg D1 Q3W, maximum tolerated dose (MTD) has not been reached. D-EXP was conducted at 2.5mg/kg D1D8 Q3W. Forty-one pts with BC and 1 pt with non-small cell lung cancer (NSCLC) were enrolled in this study. The most common TRAEs ( >10%, all grade/≥ G3) were leukopenia (67%/24%), neutropenia (55%/33%), anemia (55%/26%), thrombocytopenia (60%/24%), nausea (38%/0%), vomiting (38%/0%), stomatitis (31%/2%), asthenia (29%/0%), hypokalemia (21%/5%), aspartate aminotransferase increased (19%/0), alanine aminotransferase increased (19%/0%), decreased appetite (19%/0%), hypertriglyceridemia (19%/0%), hyperglycemia (19%/0%), hyperglycemia (17%/0%), weight decreased (14%/0%), diarrhea (12%/0%), epistaxis (12%/0%), hypercholesterolemia (12%/0%). No ILD was observed. Twenty-four pts. were evaluable for efficacy (at least 1 tumor assessment). Updated information will be provided during the meeting. Conclusions: BL-B01D1 demonstrated encouraging efficacy in metastatic/locally advanced breast cancer that have failed standard of care, especially in pts with TNBC. The safety profile showed adequate safety and tolerability. Clinical trial information: NCT05470348. Efficacy in Patients with Breast Cancer 1 Including pts whose PRs were not yet confirmed but still under treatment. Citation Format: Jiong Wu, Jian Zhang, Yiqun Du, Wen Zou, Muran Ding, Hui Yang, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Olivo, Yi Zhu. BL-B01D1, a first-in-class EGFRxHER3 bispecific antibody-drug conjugate, in patients with Locally Advanced or Metastatic Breast Cancer and other Solid Tumor: Results from a phase 1 study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-07.