Abstract PO2-04-03: BL-M07D1, an antibody-drug conjugate directed to HER2 in patients with locally advanced or metastatic Breast Cancer with HER2-positive/low-expression and other solid tumors: Results from a first-in-human phase 1 study

Abstract Background: BL-M07D1 is an anti-HER2 antibody-drug conjugate (ADC) comprised of a humanized anti-HER2 antibody, a cathepsin B cleavable linker, and a novel topoisomerase I inhibitor (Ed-04). Methods: This study included subjects with locally advanced or metastatic HER2 expressing (positive/low) breast cancer (BC) and other solid tumors. BL-M07D1 would be administered at doses of 1.0mg/kg Day 1 & Day 8 every 3 weeks (D1D8 Q3W) or 2.6, 3.2, 3.8, 4.4, 5.0, 5.6, 6.2, 6.8 and 7.4 mg/kg Day 1 every 3 weeks (D1Q3W) during dose escalation (D-ESC). A subset of patients (pts) will be enrolled in the dose-expansion phase (D-EXP) at D1 Q3W regimens. Results: As of June 25, a total of 75 pts have been treated with at least one dose of BL-M07D1, with 22 pts in the D-ESC phase and 53 in the D-EXP phase. Among the 75 pts, 1 received 1.0 mg/kg D1D8Q3W and 74 were treated on the D1Q3W schedule. Dose-limiting toxicity (DLT) was observed at 6.2mg/kg (febrile neutropenia and G3 thrombocytopenia lasting >7 days in one patient). The maximum tolerated dose (MTD) has not been reached yet. D-EXP dose levels included 3.8, 4.4, 5.0 and 5.6mg/kg D1 Q3W. This study enrolled 62 patients with BC, 6 with gastric cancer, 4 with colorectal cancer and 3 with non-small cell lung cancer. The most common TEAEs ( >10%, all grade/≥G3) were leukopenia (79%/24%), neutropenia (69%/39%), anemia (63%/11%), nausea (47%/0%), thrombocytopenia (37%/9%), vomiting (37%/1%), decreased appetite (27%/0%), lymphopenia (24%/8%), alopecia (23%/0%), asthenia (19%/0), gamma-glutamyl transferase increased (17%/0%), aspartate aminotransferase increased (17%/0%), constipation (13%/0%), diarrhea (12%/0%), hypertriglyceridemia (12%/0%), urinary tract infection (11%/1%), COVID-19 (11%/0%), occult blood positive (11%/0%), pyrexia (11%/0%). No ILD was observed. Forty-five pts with BC were evaluated for efficacy (i.e., had at least one post-baseline tumor assessment). Updated efficacy and pharmacokinetic (PK) results will be presented at the meeting. Conclusions: BL-M07D1 demonstrated encouraging efficacy in heavily pretreated HER2 expressing cancers, especially in HER2+ BC. The safety profile showed adequate safety and tolerability. Clinical trial identification: NCT05461768. Efficacy in Patients with Breast Cancer a. 8/9 pts received prior HER2-ADC with microtubule inhibitor. 1/9 pts received prior HER2-ADC with TOPI inhibitor. b. 6 pts with tumor shrinkage are still on-going. c. All pts with tumor shrinkage are still on-going. Citation Format: Erwei Song, Herui Yao, Meili Sun, Hong Zong, Rongbo Lin, Wen Zou, Muran Ding, Jing Yu, Sa Xiao, Hongwei Wang, Hai Zhu, Martin Olivo, Yi Zhu. BL-M07D1, an antibody-drug conjugate directed to HER2 in patients with locally advanced or metastatic Breast Cancer with HER2-positive/low-expression and other solid tumors: Results from a first-in-human 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 PO2-04-03.