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

PURPOSE To evaluate the efficacy and safety of the bispecific human epidermal growth factor receptor 2 (HER2)–directed antibody-drug conjugate (ADC) TQB2102 in the neoadjuvant treatment of HER2-positive breast cancer. PATIENTS AND METHODS This randomized, open-label, multicenter, phase II study (ClinicalTrials.gov identifier: NCT06198751 ) enrolled HER2-positive patients with stage II and III disease. Patients were stratified by hormone receptor status and randomly assigned (1:1) to receive 6.0 mg/kg once every 3 weeks of TQB2102 for six (cohort 1) or eight cycles (cohort 2) or 7.5 mg/kg once every 3 weeks for six (cohort 3) or eight cycles (cohort 4). The primary end point was total pathologic complete response (tpCR) rate across all four cohorts (n = 26 per cohort). When the lower limit of the 90% CI (Clopper-Pearson exact binomial test) for tpCR rate exceeded 40%, efficacy was considered better than that of the historical control. RESULTS Between February 5, 2024, and September 24, 2024, 104 patients were enrolled, with 26 patients in each cohort. The tpCR rates were 57.7% (15 of 26 [90% CI, 43.2 to 71.3]; P = .04) for cohort 1, 76.9% (20 of 26 [90% CI, 62.3 to 87.6]; P < .01) for cohort 2, 61.5% (16 of 26 [90% CI, 46.5 to 74.8]; P = .02) for cohort 3, and 69.2% (18 of 26 [90% CI, 54.6 to 81.3]; P < .01) for cohort 4. The incidence rates of grade ≥3 treatment-related adverse events were 23.1% (6 of 26) for cohort 1, 30.8% (8 of 26) for cohort 2, 30.8% (8 of 26) for cohort 3, and 26.9% (7 of 26) for cohort 4. No treatment-related deaths occurred in any groups. CONCLUSION To our knowledge, this was the first study to report the efficacy and safety of the bispecific HER2-directed ADC TQB2102 in the neoadjuvant setting for HER2-positive breast cancer. TQB2102 showed robust activity and was well-tolerated.