Efficacy and safety results of TQB2930, a HER2-targeted bispecific antibody combined with chemotherapy in patients with HER2-positive breast cancer (BC) previously treated with ≥2 line treatments: Results from a phase 1b/2 study.

Abstract

1033 Background: TQB2930 is a HER2-targeted bispecific antibody designed to bind two distinct HER2 epitopes: the extracellular domain 4 (ECD4), and the extracellular domain 2 (ECD2). In an ongoing phase 1b/2 clinical trial, TQB2930 has demonstrated favorable tolerability alongside durable responses in patients with heavily pretreated metastatic HER2-positive BC. In this context, Cohort 4 of the trial was designed to evaluate the safety and efficacy of TQB2930 in combination with chemotherapy for patients with HER2-positive BC who had received at least two prior lines of treatment. Methods: Cohort 4 enrolled patients aged ≥18 years with recurrent or metastatic HER2-positive BC who had undergone at least two prior systemic therapies. Patients with stable brain metastases were permitted. All enrolled patients received TQB2930 intravenously at a dose of 30 mg/kg every three weeks (Q3W), administered in combination with one of four investigator-selected chemotherapies (capecitabine, eribulin, gemcitabine, or vinorelbine). The primary endpoint was the overall response rate (ORR), while secondary endpoints encompassed disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and immunogenicity. Results: As of December 15, 2024, 55 patients (pts) had been treated with TQB2930 combined with chemotherapy. The median follow-up duration was 4.14 months (95% CI: 3.55–4.31). Out of 52 patients evaluable for efficacy, the ORR was 48.1% (25/52), with 88.5% (46/52) experiencing a reduction in target lesion size. Among patients who had progressed on prior T-DM1 therapy, the ORR was 36.8% (7/19), whereas patients who had failed other HER2-ADC therapies exhibited an ORR of 50% (8/16), including RC48, DS-8201, and so on. Notably, the median PFS and OS had not yet been reached, while the 6-month PFS rate was estimated at 71%. Grade ≥3 TRAEs were primarily hematological, encompassing decreased white blood cell count, neutropenia, thrombocytopenia, and infusion-related reactions. Importantly, there were no grade ≥3 cardiac toxicities, and the incidence of sinus bradycardia or QT interval prolongation was < 3%. Conclusions: The combination of TQB2930 with chemotherapy demonstrates encouraging antitumor efficacy and an acceptable safety profile in patients with HER2-positive BC who have undergone at least two prior lines of treatment. These results support the potential of TQB2930 as a novel therapeutic strategy for HER2-positive BC and underscore the need for further clinical exploration. This study was funded by Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd. Clinical trial information: NCT06202261 .