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

HER2+ metastatic breast cancer |

Image Credit: © Sebastian Kaulitzki- stock.adobe.com

The novel HER2-targeted bispecific antibody TQB2930 in combination with chemotherapy led to durable 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 (ADCs; 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 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 tyrosine kinase inhibitors (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