Efficacy and safety of neoadjuvant TQB2102 in women with locally advanced or early HER2-positive breast cancer: A randomized, open-label, multi-centre phase 2 trial.

591 Background: Standard neoadjuvant regimens for HER2-positive breast cancer include trastuzumab and pertuzumab combined with chemotherapy, and the efficacy and safety of third-generation HER2-direted antibody-drug conjugate (ADC) is unknown. TQB2102 is an anti-HER2 antibody-drug conjugate that targets two non-overlapping epitopes of HER2 (ECD2 and ECD4). It consists of a humanized HER2 IgG1 bispecific antibody conjugated to a topoisomerase I inhibitor via a cleavable linker, and the DAR value is 6. Methods: This open-label, randomized, multi-centre phase 2 study enrolled HER2-positive patients aged 18-75 years with stage II–III disease. Patients were randomly assigned to receive neoadjuvant TQB2102 6mg/kg every 3 weeks for 6 cycles or for 8 cycles. The primary endpoint was pathological complete response (pCR). Safety was analysed in patients who received at least one dose of study medication. Results: Between 05 February 2024 and 24 Sep 2024, we randomly assigned 52 patients to neoadjuvant TQB2102 6 cycles (Arm A, n=26), 8 cycles (Arm B, n=26). The baseline characteristics were well balanced; approximately 50% of the patients were hormone receptor (HR)-positive, and 63% of the patients were stage III. The pCR rate was 57.7% in Arm A (95%CI 36.9%-76.7%), 76.9% in TQB2102 Arm B (95%CI 56.3%-91%). In patients with HR positive disease, the pCR rate was 53.8% in Arm A and 58.3% in Arm B; in patients with HR negative disease, the pCR rate was 61.5% and 92.9%. Grade 3 or higher adverse events occurred 23.1% in Arm A, and 30.8% in 8 Arm B, 7.69% with increased alanine aminotransferase and aspartate transferase. Dose reduction rate and discontinuation was 3.8% and 19.2% in Arm A, 3.8% and 23.1% in Arm B, and no treatment-related deaths occurred. Conclusions: This is the first study to report the efficacy and safety of third-generation duel-HER2-directed ADC in the neoadjuvant setting for HER2-positive breast cancer. TQB2102 is highly efficient and well tolerated. Clinical trial information: NCT06198751 . pCR in All patients and by HR status. 6 cycles 8 cycles All 57.7% 76.9% HR positive 53.8% 58.3% HR negative 61.5% 92.9%