Neoadjuvant pyrotinib and inetetamab in combination with chemotherapy for locally advanced HER2-positive breast cancer (NeoPICD study): A prospective, multicenter, open-label, single-arm study.

e12627 Background: Inetetamab, a novel monoclonal antibody targeting HER2, alters the Fc region amino acids, which induces ADCC stronger than trastuzumab. Pyrotinib is a small chemical inhibitor of pan-HER receptor tyrosine kinase. The globally recommended first-line neoadjuvant treatment for HER2-positive breast cancer is chemotherapy and two large-molecule monoclonal antibodies, which have unsatisfactory benefits for 50% of patients. This study aims to investigate the effectiveness and safety of targeted medicines, specifically inetetamab and pyrotinib, in conjunction with chemotherapy for patients diagnosed with locally advanced HER2-positive breast cancer. Methods: The trial was structured as a multicenter, open-label, single-arm, prospective study. 143 treatment-naive HER2-positive locally advanced breast cancer patients were planned for the trial. Eligible patients will be administered six cycles of neoadjuvant treatment, including carboplatin (AUC=6mg/mL×min, ivgtt), doxorubicin (75mg/m 2 , ivgtt), inetetamab (initial loading dosage of 8mg/kg, maintenance dose of 6mg/kg), and pyrotinib (400mg/day, po). The surgery was conducted after the neoadjuvant phase, subsequent to a one-year course of targeted therapy with inetetamab and pyrotinib. The primary endpoint of the study is the total pathologic complete response (tpCR). The secondary endpoints include event-free survival (EFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), neurologic disease-free survival (NDFS), overall survival (OS), and safety. Results: A cohort of 70 patients was enrolled between Nov. 27, 2021 and Feb. 1, 2024. Most patients completed the six-cycle neoadjuvant therapy with inetetamab, pyrotinib, and chemotherapy. The pathological findings of 49 patients who had radical surgery revealed that 65.3% (32/49, 95% CI, 0.515-0.791) of them achieved tpCR (ypT0/Tis ypN0). The initial subgroup analysis revealed that among patients with negative hormone receptors, the rate of tpCR was 80.0% (24/30, 95% CI, 64.8-95.2). Moreover, hormone receptor was statistically determined to be an independent factor influencing the effectiveness of the new treatment regimen ( p=0.032). The prevailing grade 3 or more severe adverse events included anemia (12.8%), diarrhea (10.0%), leukopenia (4.2%), liver dysfunction (4.2%) and renal dysfunction (4.2%). As of now, no treatment-related deaths have been documented. Conclusions: The ongoing study is actively enrolling participants. Preliminary findings from the study indicate that the combination of neoadjuvant inetetamab and pyrotinib with chemotherapy has demonstrated satisfactory effectiveness and manageable side effects. This offers a promising alternative for patients with locally advanced breast cancer that is HER2-positive. Clinical trial information: NCT06234137 .