This study is the first to evaluate the efficacy and safety of the bispecific HER2-targeted antibody-drug conjugate (ADC), TQB2102, in neoadjuvant treatment of HER2-positive breast cancer. Results demonstrate that it outperforms the historical control group across different doses and cycles, while maintaining a favorable safety profile.
Literature Overview
This article, 'Efficacy and Safety of Neoadjuvant TQB2102 in Locally Advanced or Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: A Randomized, Open-Label, Multicenter, Phase II Trial,' published in the 'Journal of Clinical Oncology,' reviews and summarizes the application of the novel bispecific HER2-targeted antibody-drug conjugate (ADC), TQB2102, in the neoadjuvant treatment of HER2-positive breast cancer. The study is a randomized, open-label, multicenter phase II clinical trial aiming to evaluate the efficacy and safety of TQB2102 across various doses and treatment cycles, providing the basis for subsequent phase III studies.Background Knowledge
HER2-positive breast cancer is a molecular subtype that is highly aggressive, accounting for 15%-20% of all breast cancers. It is commonly treated with neoadjuvant therapy to reduce tumor size and increase surgical success rates. Current NCCN guidelines recommend a dual HER2 blockade regimen combining taxanes and platinum-based chemotherapy with trastuzumab and pertuzumab as the preferred neoadjuvant treatment. However, approximately 45%-50% of patients fail to achieve pathological complete response (pCR), indicating the need for more effective therapeutic strategies. In recent years, antibody-drug conjugates (ADCs) have shown significant efficacy in metastatic HER2-positive breast cancer, such as T-DXd and SHR-A1811. However, most currently available ADCs are monospecific, targeting only the trastuzumab-binding epitope. TQB2102 is a novel bispecific ADC that simultaneously targets the ECD2 (pertuzumab-binding site) and ECD4 (trastuzumab-binding site) domains of HER2. Through dual blockade of the HER2 signaling pathway and the release of a topoisomerase I inhibitor, TQB2102 demonstrates enhanced antitumor activity. This study is the first to evaluate the efficacy and safety of TQB2102 in the neoadjuvant setting, providing new research directions and potential alternative therapies for the treatment of HER2-positive breast cancer.
Research Methods and Experiments
This phase II clinical trial (NCT06198751) was conducted across five cancer centers in China and enrolled patients with stage II and III HER2-positive breast cancer. Patients were stratified according to hormone receptor (HR) status and were randomly assigned to receive TQB2102 at different doses and cycles: 6.0 mg/kg for six cycles (Cohort 1) or eight cycles (Cohort 2), and 7.5 mg/kg for six cycles (Cohort 3) or eight cycles (Cohort 4). The primary endpoint was total pathological complete response rate (tpCR), with efficacy considered superior to historical controls if the lower bound of the 90% confidence interval exceeded 40%. Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), event-free survival (EFS), invasive disease-free survival (IDFS), and safety. Safety assessments included treatment-related adverse events (TRAEs) and dose adjustments. All patients received at least one dose of TQB2102 and underwent pathological evaluation post-treatment.Key Conclusions and Perspectives
Research Significance and Prospects
This study represents the first systematic evaluation of the efficacy and safety of a bispecific HER2-targeted ADC in the neoadjuvant setting, laying the foundation for larger phase III studies. Although TQB2102 demonstrated lower efficacy in HER2 IHC 2+ patients, it showed higher tpCR rates in HER2 3+ and HR-negative populations, suggesting it may be more beneficial for specific subgroups. Future studies should explore optimal usage strategies in different subtypes and evaluate its combination with traditional chemotherapy or immune checkpoint inhibitors. Additionally, personalized treatment approaches based on HER2 expression levels and HR status warrant further investigation.
Conclusion
This study is the first to assess the efficacy and safety of the novel bispecific HER2-targeted antibody-drug conjugate (ADC) TQB2102 in neoadjuvant treatment of HER2-positive breast cancer. Results show that in all cohorts, regardless of dose or treatment cycle, the tpCR rate surpassed the historical control threshold of 40%, with a manageable safety profile and low incidence of adverse events. Notably, the 6.0 mg/kg eight-cycle regimen achieved the highest tpCR rate (76.9%) with favorable safety, and has been selected as the recommended regimen for phase III trials. The study also revealed that TQB2102 exhibited particularly strong efficacy in HR-negative patients, suggesting potential advantages in specific subpopulations. These findings offer a promising new therapeutic strategy for neoadjuvant treatment of HER2-positive breast cancer and pave the way for the application of next-generation ADCs in preoperative therapy.
