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]; = .04) for cohort 1, 76.9% (20 of 26 [90% CI, 62.3 to 87.6]; < .01) for cohort 2, 61.5% (16 of 26 [90% CI, 46.5 to 74.8]; = .02) for cohort 3, and 69.2% (18 of 26 [90% CI, 54.6 to 81.3]; < .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.