HER2-expressing breast cancer |
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Findings from the phase 2 study (CTR20241422) demonstrated that treatment with the novel HER2-targeted antibody-drug conjugate (ADC) BB-1701 produced efficacy with a manageable safety profile in patients with locally advanced or metastatic, HER2-positive or HER2-low breast cancer previously treated with a HER2-directed ADC containing a topoisomerase I inhibitor.
Data presented at the 2025 ASCO Annual Meeting showed that efficacy-evaluable patients (n = 28) achieved an objective response rate (ORR) of 28.6%, which included a confirmed partial response (PR) rate of 21.4% and an unconfirmed PR rate of 7.1%. The disease control rate (DCR) was 78.6%, with 50.0% of patients achieving stable disease (SD); 21.4% had a best response of progressive disease (PD). In the subset of patients with HER2-low/hormone receptor–positive disease (n = 17), the ORR was 35.3%, with a confirmed PR rate of 29.4% and a DCR of 82.3%. The SD and PD rates in this subgroup were 47.1% and 17.6%, respectively.
“The preliminary results from this study demonstrate the potential of BB-1701 as a new treatment option for patients with breast cancer previously treated with an HER2-[directed] ADC with [a] topoisomerase I inhibitor cytotoxin [payload], warranting further investigation,” lead study investigator Xiaoxiang Guan, MD, PhD, of the First Affiliated Hospital of Nanjing Medical University in China, and colleagues wrote in a poster presentation of the data.
BB-1701 Background and Phase 2 Study Design
The ongoing, open-label, single-arm phase 2 trial is evaluating BB-1701, a HER2-targeting ADC containing an eribulin payload, in patients with locally advanced or metastatic breast cancer characterized by high or low HER2 expression who experienced disease progression on a prior HER2-directed ADC containing a topoisomerase I inhibitor payload. Eligible patients were at least 18 years of age, had an ECOG performance status of less than 2, and had at least 1 measurable lesion per RECIST 1.1 criteria. HER2 expression was confirmed by immunohistochemistry (IHC) prior to enrollment using archived tissue samples.
Patients received BB-1701 at a fixed dose of 1.6 mg/kg administered intravenously once every 3 weeks. Tumor assessments were performed per RECIST 1.1 criteria at baseline and then every 6 weeks (±7 days) after the start of treatment. Safety was monitored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
The primary end point of the study was ORR. Secondary objectives included evaluating the safety and tolerability of the agent, determining secondary efficacy outcomes, and characterizing the pharmacokinetic profile of BB-1701.
As of the May 9, 2025, data cutoff, 31 patients were enrolled. The median age was 54.0 years (range, 39-68), and all participants were female and of Asian descent. A majority of patients (77.4%) had an ECOG performance status of 1. HER2-low expression was reported in 74.2% of patients, and 25.8% had HER2-high expression. Hormone receptor–positive disease was reported in 64.5% of participants. The median number of prior systemic therapy lines was 4.0 (range, 1-6), with 71.0% of patients having received 4 or more lines of prior treatment.
Safety Analysis
Among the 31 patients treated, the most common all-grade treatment-emergent adverse effects (TEAEs) reported in at least 10% of patients included peripheral neuropathy (38.7%), increased aspartate aminotransferase levels (35.5%), decreased platelet count (29.0%), increased alanine aminotransferase levels (25.8%), and decreased white blood cell count (22.6%), hypokalemia (19.3%), anemia (16.1%), increased blood lactate dehydrogenase levels (16.1%), alopecia (12.9%), hypoalbuminemia (12.9%), hypertriglyceridemia (12.9%, and upper respiratory tract infection (12.9%).
Grade 3 TEAEs of peripheral neuropathy, decreased neutrophil count, type 2 diabetes mellitus, myocardial injury, anemia, hypokalemia, and humerus fracture were reported in 1 patient each (3.2%). One patient experienced grade 4 hypercalcemia. There were no reports of grade 5 TEAEs or any-grade interstitial lung disease (ILD).
Serious TEAEs comprised peripheral neuropathy, hypercalcemia, type 2 diabetes, hypoalbuminemia, myocardial injury, hypokalemia, and humerus fracture. One patient discontinued treatment due to peripheral neuropathy.
Reference
Guan X, Shi Y, Yang J, et al. 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. J Clin Oncol. 2025;43(suppl 16):1093. doi:10.1200/JCO.2025.43.16_suppl.1093