360P Neoadjuvant inetetamab combined with pertuzumab, paclitaxel and carboplatin for locally advanced HER2-positive breast cancer: Primary analysis of a phase II study

Inetetamab is a neotype HER2-targeted monoclonal antibody with amino acids modified Fc segment which optimizes the antibody-dependent cellular cytotoxicity effect. However, robust evidence evaluating the combination of inetetamab combined with pertuzumab, paclitaxel and carboplatin (TCbIP) for neoadjuvant therapy is still lacking. This study aimed to evaluate the efficacy and safety of TCbIP as a neoadjuvant therapy for patients with locally advanced (LA) HER2-positive breast cancer. This phase II trial included female patients with histologically confirmed stage IIA to IIIC HER2-positive primary invasive breast cancer. Eligible patients received TCbIP treatment every three weeks for a maximum of six cycles followed by surgery. The primary endpoint was pathologic complete response (pCR, ypT0/is ypN0) rate. Key secondary endpoints included near pCR (npCR, residual breast disease <1cm) rate, objective response rate (ORR) and safety. From November 2021 to May 2023, 28 patients were enrolled in the trial. One patient received one cycle of the study treatment and was lost to follow-up without surgery, and four patients received one cycle of the study treatment and were still in treatment, leaving 23 patients in the ITT population. Among these 23 patients (82.6% in stage III), 16 patients completed the study treatment and surgery (PP population) and six patients were still undergoing neoadjuvant treatment. The ORR was 91.3% (21/23) in the ITT population and 93.8% (15/16) in the PP population. Among the 16 patients in the PP population, 10 patients (62.5%) achieved pCR. A total of 14 patients (87.5%) achieved npCR. For patients with hormone receptor (HR) negative and positive tumors, the pCR rates were 88.9% (8/9) and 28.6% (2/7), respectively. The most common grade 3 adverse event was neutropenia (25.0%). No significant reduction in the left ventricular ejection fraction was observed in any patient. Neoadjuvant therapy with TCbIP has shown promising efficacy and manageable toxicity in patients with HER2-positive LA breast cancer.