TQB2930 is Well Tolerated, Elicits Antitumor Activity in HER2+ Advanced Breast Cancer

Qingyuan Zhang, MD, PhD

Treatment with the HER2-targeted bispecific antibody TQB2930 was well tolerated and led to preliminary antitumor activity in patients with HER2-positive advanced breast cancer who received prior standard therapy, according to data from a phase 1b trial (NCT06202261) presented at the 2024 ASCO Annual Meeting.¹

Findings showed that no dose-limiting toxicities occurred at any of the 3 dose levels evaluated during the dose-escalation and -expansion study. Among all patients (n = 34), the respective rates of any-grade and grade 3 or higher treatment-related adverse effects (TRAEs) were 82.4% and 8.8%.

Efficacy-evaluable patients (n = 31) achieved an overall response rate (ORR) of 25.8%, which was comprised of 8 patients who all experienced a partial response (PR). Five patients had a confirmed PR, and 3 patients had an unconfirmed PR. The stable disease (SD) rate was 54.8%, and the progressive disease (PD) rate was 12.9%. The disease control rate (DCR) was 80.6%. Notably, 6.5% of patients were not evaluable for response.

“TQB2930 is well tolerated and has demonstrated promising single-agent antitumor activity in [patients with] HER2-positive breast cancer who have [progressed on] standard anti-HER2 therapies, including multiple lines of prior HER2-targeted agents,” lead study author Qingyuan Zhang, MD, PhD, of the Department of Medical Oncology at Harbin Medical University Cancer Hospital in China, and colleagues, wrote in a poster presentation of the data. “These early signs of activity support the further exploration of combination therapy of TQB2930.”

TQB2930 is designed to bind to 2 distinct HER2 epitopes: ECD4, which is the same domain as trastuzumab (Herceptin), and ECD2, which is the same domain as pertuzumab (Perjeta).

The phase 1b, open-label trial enrolled patients with HER2-expressing and -amplified breast cancer who had received prior standard therapy. Patients needed to be between 18 and 75 years of age with a life expectancy of more than 3 months and an ECOG performance status of 0 or 1.²

Specifically in phase 1b, patients were required to have cytologically or histopathologically confirmed advanced malignancies, with priority given to patients with tumors harboring HER2 expression or amplification. Patients needed to have progressed on standard treatment or not have standard treatment available, and at least 1 evaluable lesion per RECIST 1.1 criteria was required.²

During dose escalation, TQB2930 was administered at 10 mg/kg once per week, 20 mg/kg once every 2 weeks, or 30 mg/kg once every 3 weeks. In dose expansion, the bispecific antibody was dosed at 20 mg/kg once every 2 weeks or 30 mg/kg once every 3 weeks.¹

The study’s primary end points were safety and determining the maximum tolerated or maximum delivered dose. Secondary end points included immunogenicity, pharmacokinetics, and ORR per RECIST v1.1 criteria.

As of the December 20, 2023, data cutoff, 34 patients received TQB2930 at either 10 mg/kg (n = 3), 20 mg/kg (n = 16), or 30 mg/kg (n = 15). Patients had received a median of 3 prior lines of therapy (range, 0-8). The median number of prior lines of HER2-targeted therapies was 2 (range, 0-8).

Additional data showed the median progression-free survival in the overall population was 5.5 months (95% CI, 3.58–not evaluable).

Among efficacy-evaluable patients who received TQB2930 at 10 mg/kg once per week (n = 3), the ORR was 33.3%. The SD rate was 33.3%, and 1 patient was not evaluable. Patients treated at 20 mg/kg once every 2 weeks who were evaluable for efficacy (n = 16) experienced an ORR of 12.5%, an SD rate of 56.3%, a PD rate of 25.0%, and a DCR of 68.8%.

In those evaluable for efficacy at the 30-mg/kg dose (n = 12), the ORR was 41.7%. The SD rate was 58.3%, and no patients in this cohort had PD, translating to a DCR of 100%.

Additional safety data from the overall population showed that the most common any-grade TRAEs included nausea (8.8%), decreased neutrophil count (20.6%), infusion reaction (26.5%), increased serum creatinine (11.8%), diarrhea (5.9%), positive occult blood (26.5%), decreased white blood cell count (23.5%), increased aspartate aminotransferase (8.8%), increased total bilirubin (8.8%), and anemia (14.7%).

Grade 3 or higher TRAEs included decreased neutrophil count and anemia at 2.9% each.

References

1. 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
2. A study of TQB2930 for injection monotherapy or combination therapy in patients with recurrent/​metastatic breast cancer. ClinicalTrials.gov. Updated March 12, 2024. Accessed July 16, 2024. https://clinicaltrials.gov/study/NCT06202261