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.
Authors: Fei Ma, Xiaoxiang Guan, Jingfen Wang, Herui Yao, Xian Wang, Erika P. Hamilton, Yehui Shi, Xinjun Liang, Nong Xu, Huoling Tang, Xiangzhu Tian, Yuhong Zhou, Ziping Wei, Pamela N. Munster
Journal: Journal of Clinical Oncology (2024)

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 &lt;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 .