Abstract P5-07-20: A prospective, open-label, single-arm phase II clinical study of inetetamab in combination w/ pyrotinib & albumin-bound paclitaxel for neoadjuvant treatment of patients with HER2+ early & locally advanced breast cancer: updates on clinical trial

Abstract Background: Chemotherapy combined with dual anti-HER2 target therapy has become the standard neoadjuvant therapy regimen for HER2+ breast cancer. Patients achieving pathological complete response (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 >20 mm or had confirmed axillary lymph node metastasis. Patients received an initial dose of Inetetamab at 8 mg/kg over 90 minutes via IV infusion, followed by 6 mg/kg over 30 to 90 minutes via IV infusion every 3 weeks (q3w). Pyrotinib was administered at 400 mg orally every day, and albumin-bound Paclitaxel at 125 mg/m2 via IV on days 1, 8, and 15, every 3 weeks (q3w). Patients received the above treatment every 3 weeks for a total of 4 cycles, followed by surgery.After surgery, EC (90 mg/m2 of Epirubicin Hydrochloride and 600 mg/m2 of Cyclophosphamide) was administered every 21 days (q21 days) for 4 cycles, followed by maintenance treatment with trastuzumab combined with pertuzumab for 1 year. Radiotherapy and endocrine therapy were provided to the patient according to the specific situation. The primary endpoint was pathological complete response (pCR).Results: Until September 20, 2024, 22 patients were enrolled, of which 20 had completed surgical treatment. The median age of enrolled patients was 52 years (range: 35-61 years). 50.0% (10 cases) of patients achieved RCB grade 0 (pCR), 20.0% (4 cases) achieved RCB grade I, 25% (5 cases) achieved RCB grade II, and 5% (1 case) achieved RCB grade III. Of the 20 patients, 55.0% (11 cases) were HR+/HER2+, with 36.4% (4 cases) achieving pCR. Among the 9 HR-/HER2+ patients, 66.7% (6 cases) 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 pathological complete response (pCR) rate in HER2+ breast cancer patients reaches 50.0%, and even 36.4% in HR+ patients. Interestingly, 4 out of these 20 patients achieved near-pathological complete response (near-pCR). We suggest that these 4 patients would more likely achieve pCR if treated with a 6-cycle regimen, which can boost the pCR rate to 70% (14/20) in HER2+ 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%, respectively. In contrast, in the NeoALTTO and PHEDRA studies of the H+L or H+Py regimen, the pCR increased by 18.9% and 17.7%, respectively. This indicates that the combination of large and small molecules with dual-target neoadjuvant therapy for HR+/HER2+ breast cancer is significantly better than monoclonal antibody dual-target therapy.Therefore, Inetetamab, Pyrotinib, and albumin-bound paclitaxel are potentially effective new adjuvant treatments for HER2+ breast cancer with a superior pCR rate. Citation Format: Jiang Wu, Fengqiang Cui, Yuqing Yang, Jing Yu, Jixin Yang, Lei Wang, Dongdong Xu, Wenyu Hu, Jialing Luo, Wen Ma, Nanlin Li. A prospective, open-label, single-arm phase II clinical study of inetetamab in combination w/ pyrotinib & albumin-bound paclitaxel for neoadjuvant treatment of patients with HER2+ early & locally advanced breast cancer: updates on clinical trial [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-07-20.