News|Articles|December 2, 2025
New-Generation ADC Elicits Responses in Neoadjuvant HER2+ Breast Cancer
Author(s)Andrea Eleazar, MHS
Fact checked by: Sabrina Serani
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Key Takeaways
- TQB2102 demonstrated robust antitumor activity and a favorable safety profile in a phase 2 trial for HER2-positive breast cancer.
- The 8-cycle 6.0 mg/kg regimen achieved the highest pathologic complete response rate among the four cohorts.
TQB2102 shows promising antitumor activity and safety as a neoadjuvant therapy for HER2-positive breast cancer in a recent phase 2 trial.
The bispecific HER2-directed antibody-drug conjugate (ADC) TQB2102 has demonstrated robust antitumor activity and a positive safety profile in the phase 2 TQB2102-II-01 trial (NCT06198751), showing promise as a neoadjuvant treatment for HER2-positive (HER2+) breast cancer.1
The study enrolled patients into 1 of 4 cohorts receiving different doses of TQB2102 via intravenous infusion: 6.0 mg/kg once every 3 weeks for 6 (cohort 1) or 8 cycles (cohort 2) or 7.5 mg/kg once every 3 weeks for 6 (cohort 3) or 8 cycles (cohort 4). The total pathologic complete response (tpCR) rates for cohorts 1, 2, 3, and 4 were 57.7% (90% CI, 43.2%–71.3%; P =.04), 76.9% (90% CI, 62.3%–87.6%; P <.01), 61.5% (90% CI, 46.5%–74.8%; P =.02), and 69.2% (90% CI, 54.6%–81.3%; P <.01), respectively, with the 8-cycle 6.0 mg/kg dosing administration (cohort 2) exhibiting the highest tpCR rate.
Regarding safety, TQB2102 was well tolerated by patients, with no occurrence of treatment-related deaths. For cohorts 1, 2, 3, and 4, the respective incidence rates of grade ≥3 treatment-related adverse events were 23.1%, 30.8%, 30.8%, and 26.9%. Across the cohorts, the incidence rate was 27.9%. One case of interstitial lung disease occurred in cohort 4.
About the Phase 2 Trial and Next Steps
The TQB2102-II-01 trial was a randomized, open-label, multicenter trial conducted in China.2 Motivated by a need for more effective anti-HER2 ADCs in the neoadjuvant setting, the objective of the trial was to evaluate the efficacy and safety of TQB2102 as neoadjuvant therapy for adult patients with HER2+ stage II and III breast cancer.
TQB2102 differentiates itself from other investigational third-generation ADCs for HER2+ breast cancer, such as trastuzumab deruxtecan (T-DXd; Enhertu) and SHR-A1811, through its optimized design characteristics and mechanism of action. As a bispecific ADC, the agent achieves a dual HER2 signaling blockade through targeting 2 HER2 nonoverlapping epitopes, ECD2 and ECD4, which is intended to enhance antitumor activity.
“As a bispecific HER2-directed ADC, TQB2102 can recognize the HER2 protein by binding to both the trastuzumab [Herceptin] and pertuzumab [Perjeta] binding sites,” said study authors Li et al in the Journal of Clinical Oncology publication.1 “To our knowledge, our study was the first to reveal that [8] cycles of single-agent TQB2102 could achieve a pCR rate of 73.1% in HER2[+] patients with [breast] cancer, which was numerically superior to the pCR rates of other ADCs and those of standard chemotherapy plus trastuzumab and pertuzumab reported in other previous trials.”
In the trial, 104 patients were enrolled between February 5, 2024, and September 24, 2024, and randomly assigned 1:1 across 4 cohorts, with 26 patients per cohort. An exploratory comparison between the cohorts further confirmed the superiority of the 8-cycle 6.0 mg/kg regimen received by cohort 2 vs the 6-cycle regimen received by cohort 1. While not statistically significant (P =.21), this comparative analysis revealed a 13.5 percentage-point difference in pCR rate between the 2 cohorts.
Considering these results, a larger randomized phase 3 trial (NCT07043725) of TQB2102 in the neoadjuvant setting has been initiated, which will carry forward the 8-cycle regimen for evaluation against trastuzumab, pertuzumab, and chemotherapy in patients with HER2+ breast cancer.3
REFERENCES
1. Li JJ, Zhang WJ, Zeng XH, et al. 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. J Clin Oncol. Published online November 25, 2025:JCO2501153-JCO2501153. doi:10.1200/jco-25-01153
2. A study of neoadjuvant treatment with TQB2102 for injection for human epidermal growth factor receptor 2 (HER2) positive breast cancer. ClinicalTrials.gov. Updated August 19, 2025. Accessed December 1, 2025. https://www.clinicaltrials.gov/study/NCT06198751
3. A clinical study of neoadjuvant treatment with TQB2102 for injection for human epidermal growth factor receptor 2 (HER2) positive breast cancer. ClinicalTrials.gov. Updated September 23, 2025. Accessed December 1, 2025. https://www.clinicaltrials.gov/study/NCT07043725
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