A prospective, open-label, single-arm phase II clinical study of inetetamab in combination with pyrotinib and albumin-bound paclitaxel for the neoadjuvant treatment of patients with HER2+ early and locally advanced breast cancer.

e12635 Background: Chemotherapy combined with dual anti-HER2 target therapy has become the standard neoadjuvant therapy regimen for HER2+ breast cancer. Patients achieving pCR have a relatively better prognosis. Inetetamab (Septin) is an innovative HER2 monoclonal antibody drug developed in China. It has been proven to delay the progression of HER2+ metastatic breast cancer patients and bring survival benefits. The purpose of this study was to explore the efficacy and safety of Inetetamab, Pyrotinib and Albumin-bound Paclitaxel in the neoadjuvant treatment of HER2+ breast cancer. Methods: This phase II trial included patients with HER2+ early or locally advanced breast cancer whose tumor size was>20mm or confirmed axillary lymph node metastasis. Patients receive Inetetamab initial dose of 8 mg/kg over 90 minutes IV infusion, followed 6 mg/kg over 30 to 90 minutes IV infusion q3w, Pyrotinib 400 mg orally every day and Albumin-bound Paclitaxel 125mg/m2, IV, D1/8/15, q3w. Patients receive above treatment every 3 weeks for a total of 4 cycles, followed by surgery. After surgery, EC (90mg/m2 of Epirubicin Hydrochloride, 600mg/m2 of Cyclophosphamide, q21 days, 4 cycles) was administered, followed by maintenance treatment with trastuzumab combined with pertuzumab for 1 year. And provide radiotherapy and endocrine therapy to the patient according to the specific situation. The primary endpoint was pathological complete response (pCR). Results: Until February 4, 2024, 18 patients were enrolled, of which 15 had completed surgical treatment. The median age of enrolled patients was 49 years (35-60 years). 66.7% (10 cases) of patients achieved RCB grade 0 (pCR), 26.7% (4 cases) achieved RCB grade I, 6.7% (1 case) achieved RCB grade II. Of the 15 patients, 73.3% (11 cases) were HR+/HER2+, with 72.7% (8 cases) achieved pCR. Among the 4 HR-/HER2+ patients, 50% (2 case) achieved pCR. HR+/HER2+ patients were more likely to achieve pCR than HR-/HER2+ patients. No severe (grade 3/4) toxicity was observed in any patients. Conclusions: Our current data show that the pCR rate in HER2+ breast cancer patients reaches 66.7%, and even 72.7% in HR+ patients. In the previous Neosphere and PEONY studies of the H+P dual target regimen, the pCR of HR+/HER2+patients increased by only 6% and 8.3%, while in the NeoALTTO and PHEDRA studies of the H+L or H+Py regimen, the pCR increased by 18.9% and 17.7%, indicating that the combination of large and small molecules with dual target neoadjuvant therapy for HR+/HER2+ breast cancer was significantly better than that of the monoclonal antibody dual target therapy. Therefore, Inetetamab, Pyrotinib and albumin-bound paclitaxel is a potential effective new adjuvant treatment for HER2+ breast cancer, especially for HR+ patients. Clinical trial information: NCT054444998 .