TQB2930 Plus Chemo Drives Responses in Pretreated HER2+ Metastatic Breast Cancer

The novel HER2-targeted bispecific antibody TQB2930 in combination with chemotherapy led to responses and displayed an acceptable safety profile in patients with HER2-positive metastatic breast cancer who received at least 2 prior HER2-targeted therapies, according to data from cohort 4 of a phase 1b/2 trial (NCT06202261).¹

Findings presented at the 2025 ASCO Annual Meeting demonstrated that efficacy-evaluable patients (n = 52) achieved an overall response rate (ORR) of 48.1%, and 88.5% of patients experienced target lesion shrinkage. In patients previously treated with ado-trastuzumab emtansine (T-DM1; Kadcyla; n = 19), the ORR was 36.8%; patients who received other HER2-directed antibody-drug conjugates (n = 16) had an ORR of 50%.

At a median follow-up of 4.14 months (95% CI, 3.55-4.31), the median progression-free survival (PFS) and overall survival (OS) had not been reached as of the December 15, 2024, data cutoff. The estimated 6-month PFS rate was 71%.

Regarding safety (n = 55), most grade 3 of higher treatment-related adverse effects (TRAEs) were hematological, and no grade 3 or higher cardiac toxicities were reported. Sinus bradycardia or QT interval prolongation occurred in less than 3% of patients. The rate of any-grade TRAEs was 94.5%, and serious TRAEs occurred at a rate of 23.6%. TRAEs led to treatment discontinuation in 5.5% of patients.

“These results support the potential of TQB2930 as a novel therapeutic strategy for HER2-positive breast cancer and underscore the need for further clinical exploration,” lead study author Qingyuan Zhang, MD, PhD, of the Breast Department at Harbin Medical University Cancer Hospital in China, and colleagues wrote in a poster presentation of the data.

TQB2930 Background and Cohort 4 Breakdown

The bispecific antibody is designed to bind to the ECD4 and ECD2 HER2 epitopes. Previously reported data from the phase 1b/2 trial presented at the 2024 ASCO Annual Meeting showed that no dose-limiting toxicities were reported with TQB2930 monotherapy across 3 evaluated dose levels (n = 34), and the rates of any-grade and grade 3 or higher TRAEs were 82.4% and 8.8%, respectively.² Evaluable patients (n = 31) experienced an ORR of 25.8% with TQB2930 monotherapy, with a disease control rate (DCR) of 80.6%.

In cohort 4, investigators evaluated the addition of various chemotherapy regimens to the bispecific antibody.¹ This cohort included patients with recurrent or metastatic HER2-positive breast cancer who received at least 2 prior anti-HER2 therapies, had at least 1 measurable lesion per RECIST 1.1 criteria, and had an ECOG performance status of 0 or 1. Patients with stable brain metastases were allowed to participate.

All patients received TQB2930 at 30 mg/kg given once every 3 weeks. Chemotherapy options included vinorelbine at 25 mg/m² on days 1 and 8 of each 21-day cycle; capecitabine at 1000 mg/m² twice per day on days 1 to 14 of each 21-day cycle; gemcitabine at 1000 mg/m² on days 1 and 8 of each 21-day cycle; or eribulin at 1.4 mg/m² on days 1 and 8 of each 21-day cycle.

Safety and ORR served as the primary end points for cohort 4. DCR, duration of response, PFS, OS, pharmacokinetics, and immunogenicity were secondary end points.

Enrolled patients (n = 55) had a median age of 53.0 years (range, 34-74), and 94.55% had HER2-positive disease. Most patients had an ECOG performance status of 1 (67.27%). Sites of metastatic disease included liver (34.55%), brain (18.18%), and lung (52.73%).

Additionally, 50.91% of patients received more than 2 prior lines of therapy. Prior treatments comprised trastuzumab (Herceptin; 96.36%), pertuzumab (Perjeta; 41.82%), T-DM1 (40.00%), pyrotinib (Irene; 69.09%), other HER2-directed ADCs (69.09%), other HER2-targeted TKIs (10.91%), and other HER2-directed monoclonal antibodies or bispecific antibodies (25.45%).

Additional Safety Data

The most common any-grade TRAEs reported in at least 20% of patients included decreased neutrophil count (70.9%), decreased white blood cell count (69.1%), anemia (58.2%), thrombocytopenia (41.8%), elevated aspartate aminotransferase levels (38.2%), elevated alanine aminotransferase levels (36.4%), infusion-related reaction (25.5%), decreased appetite (23.6%), diarrhea (21.8%), asthenia (20.0%), and hypokalemia (20.0%).

Grade 3 or higher TRAEs reported in at least 2 patients included decreased neutrophil count (58.2%), decreased white blood cell count (52.7%), thrombocytopenia (7.3%), infusion-related reaction (5.5%), and diarrhea (3.6%).

References

1. Zhang Q, Zhao W, Wang J, et al. 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. J Clin Oncol. 2025;43(suppl 16):1033. doi:10.1200/JCO.2025.43.16_suppl.1033
2. Zhang Q, Wang J, Li L, et al. Preliminary safety and efficacy of TQB2930, a HER2-targeted bispecific antibody in patients with advanced breast cancer: results from a phase 1b study. J Clin Oncol. 2024;42(suppl 16):1026. doi:10.1200/JCO.2024.42.16_suppl.1026