A phase II study to evaluate the safety and efficacy of BB-1701 in subjects with HER2 expression locally advanced/metastatic breast cancer previously treated with HER2-ADC containing TOP-I inhibitor.

Abstract

1093 Background: BB-1701 is an HER2-targeting antibody-drug conjugate (ADC) containing eribulin. In phase I study, BB-1701 had shown promising antitumor activity in breast cancer (BC) patients with HER2 high/low expression and manageable safety profile. Currently, there are no approved treatment options for metastatic BC patients with high/low expression who have received HER2-ADC containing TOP-I inhibitor, especially for trastuzumab deruxtecan. We report the preliminary efficacy and safety results from the ongoing phase 2 study of BB-1701 in advanced or metastatic breast cancer patients with HER2 expression previously treated with HER2-ADC containing TOP-I inhibitor. Methods: Patients enrolled were ≥18 years of age; had confirmed locally advanced/metastatic HER2 expressing breast cancer; disease progression after previous HER2-targeting ADC (containing TOP-I inhibitor) therapy; an ECOG PS < 2; and measurable lesion(s) (per RECIST v1.1). HER2 expression was confirmed by IHC before patient enrollment. BB-1701 is administered at 1.6 mg/kg Q3W. Results: As of 28 January 2025, 23 patients with HER2 high/low-expressing breast cancer have been enrolled and treated. Median age is 51 years, all patients are female, and 26.1%/73.9% patients have ECOG PS 0/1. The median number of prior systemic therapy lines was 4.0, 21.7%/78.3% HER2 status are high expression/low expression. All patients experienced at least one treatment-emergent adverse events (TEAEs). The most common (≥10%) all grade TEAES are neutrophil count decreased, platelet count decreased, Aspartate aminotransferase increased, and white blood cell count decreased. One grade 3 TEAEs is peripheral neuropathy, and another grade 3 TEAE is neutrophil count decreased. There has been no grade 4 or grade 5 events as of data cut-off date. One treatment emergent serious adverse event is peripheral neuropathy. Of the 23 patients, 14 were evaluable for efficacy. Among 14 evaluated patients, 4 patients achieved partial response (PR) and 9 patients had stable disease (SD), with disease control rate (DCR) of 92.8%. Among 3 HER2 high-expressing patients who were previously treated with trastuzumab deruxtecan, 1 patient achieved PR and 2 patients had SD with DCR of 100.0%. Among 8 HER2 low-expressioning (IHC 1+) patients, 3 patients achieved PR (2 patients received prior trastuzumab deruxtecan and 1 patient received prior SHR-A1811) and 4 patients had SD with DCR of 87.5%. More data will be presented at the ASCO meeting. Conclusions: BB-1701 shows promising antitumor activity and a manageable safety profile in HER2 expressing breast cancer patients who had previously been treated with HER2-ADC (containing TOP-I inhibitor). Clinical trial information: CTR20241422 .