Editor’s Note: Antibody–drug conjugates (ADCs) targeting HER2 have already transformed the treatment landscape in advanced breast cancer and are now making their way into early-stage settings. At the 2025 ASCO Annual Meeting, Professor Junjie Li from Fudan University Shanghai Cancer Center presented results from a phase II clinical study investigating a novel HER2 bispecific ADC, TQB2102, in the neoadjuvant treatment of HER2-positive early breast cancer. The study delivered striking pathological complete response (pCR) results, suggesting strong potential for clinical impact. Below is an on-site interview with Professor Li, summarizing the key findings.Oncology Frontier: Could you share the background and key results of the TQB2102 study you presented at ASCO?
Professor Junjie Li: It was a great honor to present this study at ASCO on behalf of the national multicenter research team led by Professor Zhimin Shao. TQB2102 is a bispecific HER2-targeting ADC that binds to both ECD2 and ECD4 domains of the HER2 receptor. It uses a cleavable linker and delivers a topoisomerase I inhibitor payload, with a drug–antibody ratio (DAR) of 6.
This year’s ASCO featured multiple presentations on TQB2102: two posters and one oral presentation. Professor Ruihua Xu from Sun Yat-sen University Cancer Center presented the oral report showing that TQB2102 demonstrates promising antitumor activity across several HER2-positive solid tumors, including breast, colorectal, and gastric cancers. Additionally, Professor Shusun Wang’s poster highlighted encouraging efficacy in HER2-low breast cancer.
To further assess the value of TQB2102 in the neoadjuvant setting for breast cancer, Professors Zhimin Shao, Qingyuan Zhang, and Xiaohua Zeng initiated a multicenter phase II study. The study enrolled patients with stage II–III HER2-positive breast cancer, randomized to receive either six cycles or eight cycles of TQB2102 as neoadjuvant monotherapy at doses of 6 mg/kg or 7 mg/kg every three weeks (Group A and Group B, respectively). In Professor Xu’s earlier dose-escalation phase I study, both 6 mg/kg and 7.5 mg/kg were deemed feasible.
In this current study, the pCR rate for the six-cycle regimen was 59.6%, while the eight-cycle regimen achieved 73.1%. The treatment showed favorable tolerability, with grade ≥3 adverse events occurring in 27.9% of patients overall.
Given that T-DXd has recently shown positive results in the neoadjuvant DESTINY-Breast study, we are eagerly awaiting further comparison data. While direct comparisons between single-target and bispecific HER2 ADCs are not yet available, the findings here are promising. Notably, among patients who received eight cycles of TQB2102 at 6 mg/kg, the pCR rate in hormone receptor–negative patients reached an impressive 92.9%, which is among the highest reported in evidence-based literature to date.
Currently, a national multicenter phase III trial is underway to further evaluate TQB2102 in HER2-positive early breast cancer in the neoadjuvant setting. We hope these future results will reinforce the potential of this agent to shape clinical practice and improve patient outcomes.
Oncology Frontier: In this study, how did hormone receptor (HR)-positive and HR-negative patients respond to neoadjuvant treatment with TQB2102? What are the clinical implications of these findings?
Professor Junjie Li:As we know, HR-positive and HR-negative patients often respond differently to neoadjuvant therapy, with HR-negative patients typically achieving higher pCR rates. In previous studies, neoadjuvant regimens involving various monoclonal antibodies or tyrosine kinase inhibitors—either with or without anthracyclines—have reported pCR rates ranging from approximately 18% to 35% in HR-positive patients.
In our study, the pCR rates for HR-positive patients receiving eight cycles of TQB2102 at 6 mg/kg and 7.5 mg/kg were 58.3% and 61.5%, respectively. These results are remarkably high and almost unprecedented for triple-positive breast cancer in previously reported literature.
This gives us great confidence in TQB2102’s potential. Combined with its favorable safety and tolerability profile, these findings suggest that TQB2102 could offer a highly promising neoadjuvant option for patients with HER2-positive breast cancer, including those with HR-positive disease.
Oncology Frontier: Based on the current findings, how do you envision the future clinical application of TQB2102 in neoadjuvant therapy for HER2-positive breast cancer?
Professor Junjie Li: As mentioned, we are initiating a national multicenter phase III clinical trial. The control arm will be the current standard regimen—TCbHP, which includes double chemotherapy and dual-targeted therapy with trastuzumab and pertuzumab. The experimental arm will be the eight-cycle TQB2102 regimen at 6 mg/kg.
If this phase III study yields positive results, it could lead to a major shift in clinical practice. TQB2102 has the potential to become a new standard for neoadjuvant therapy in early-stage HER2-positive breast cancer, offering more patients a chance at cure with a streamlined and effective treatment approach.
