Updated safety and antitumor activity of BB-1701 from study 101 in the multiple dose level cohort of patients with locally advanced/metastatic HER2-low expressing breast cancer.

1110 Background: BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 antibody and eribulin. After BB-1701 is internalized in HER2 expressing cancer cells, free eribulin is cleaved from the ADC by cathepsin b and causes cytotoxicity to cancer cells. The neighboring cells are affected with bystander effects, like cytotoxicity on tumor cells and non-cytotoxic effects on microenvironment by free eribulin. Here, we report updated results from the ongoing cohort expansion of the first-in-human phase I study (NCT 04257110). Methods: Patients enrolled were ≥18 years of age; had confirmed locally advanced/metastatic HER2 low-expressing (IHC 2+ and FISH negative, or IHC 1+; tested before enrollment) breast cancer; disease progression after ≥2 lines of prior standard therapies; an ECOG PS <2; and measurable lesion(s) (per RECIST v1.1). Four dose levels of BB-1701 (1.0, 1.2, 1.4 and 1.6 mg/kg) were administered during the cohort expansion. Results: As of 31 January 2024, 40 pts with HER2 low-expressing breast cancer were enrolled, 5 at 1.0 mg/kg, 20 at 1.2 mg/kg, 5 at 1.4 mg/kg and 10 at 1.6 mg/kg. Median age was 55 years, 97.5% ps were female, and 30.0%/70.0% pts had ECOG PS 0/1. The median number of prior lines of systemic therapy was 3. The most common (≥20%) all grade treatment-related adverse events (TRAEs) were peripheral neuropathy, AST increased, ALT increased, anemia, WBC decreased and hypertriglyceridemia. The most common (≥ 5%) grade 3 TRAEs were peripheral neuropathy and peripheral sensory neuropathy. There were no grade 4 or grade 5 events. Four treatment related serious adverse events were peripheral sensory neuropathy, anemia, spinal compression fracture and infusion related reaction. One patient discontinued BB-1701 treatment due to peripheral neuropathy. Of the 40 pts, 38 were evaluable for efficacy. At 1.0 mg/kg dose level, there were 2 partial response (PR), 2 stable disease (SD), with disease control rate (DCR) of 80.0% and 6-month PFS rate of 20%. At 1.2 mg/kg dose level, there were 5 PR, 11 SD with DCR of 88.9% and 6-month PFS rate of 50%. At 1.4 mg/kg dose level, there were 2 PR, 2 SD with DCR of 80.0% and 6-month PFS rate of 40%. At 1.6 mg/kg dose level, there were 1 complete response (CR), 2 PR with objective response rate of 30.0%, DCR of 60.0% and 6-month PFS rate of 50%. Among the 10 pts at 1.6 mg/kg dose level, 1 pt who had previously been treated with disitamab vedotin maintain CR and has been treated by BB-1701 for 9 months, and 1 pt who had previously been treated with trastuzumab deruxtecan maintain PR and has been treated by BB-1701 for 12 months. Conclusions: BB-1701 shows promising antitumor activity and a manageable safety profile in HER2 low-expressing breast cancer, including patients who received prior anti-HER2 ADCs. Clinical trial information: NCT04257110 .