Abstract PS09-03: Neoadjuvant zanidatamab for stage I node negative HER2 positive breast cancer

Abstract Background: The addition of trastuzumab+/-pertuzumab to chemotherapy has changed the natural history of earlyHER2+ breast cancer. However, trials with targeted therapy alone are needed to avoid acute and chronic toxicities of chemotherapy. Zanidatamab is a novel, humanized, bispecific, immunoglobulin G isotype 1-like, monoclonal antibody directed against the juxtamembrane extracellular and dimerization domains (ECD2, ECD4) of HER2. The biparatopic nature of zanidatamab results in HER2 clustering that modulates signaling and leads to immune activation. Zanidatamab has demonstrated antitumor activity in heavily pre-treated HER2 overexpressing metastatic breast cancer with an acceptable safety profile. We hypothesized that zanidatamab would be a safe and effective regimen for women with node negative stage I HER2+ BC. Methods: Patients with 1-3 cm, clinically node negative HER2+ BC were enrolled in a single-institution investigator-initiated clinical trial. Patients had HER2+ breast cancer: HER2 3+ by IHC or IHC 2+ and ISH +. Patients received six to ten doses of zanidatamab, 20 mg/kg IV every 2 weeks prior to surgery. Patients with ER+ tumors also received neoadjuvant endocrine therapy. Post-menopausal patients received letrozole 2.5 mg daily, and pre-menopausal patients received tamoxifen 20 mg daily or GNRH and letrozole 2.5 mg. The primary objective was to evaluate efficacy as determined by pathologic complete response (pCR). Secondary objectives included pathologic response by residual cancer burden (RCB), radiological response, and safety profile of zanidatamab. Results: Twenty patients with HER2+ breast cancer were enrolled. Median age was 62 years old (range 30-73). Fifteen patients had HER2 3+, and 5 HER2 2+/ISH+ tumors with a median size of 1.95 cm (range 1-3 cm) and 10 patients had tumors >2 cm. Seven patients were pre-menopausal. Six received tamoxifen and 8 letrozole. Eleven patients completed 6 cycles and 9 patients will receive 10 cycles of zanidatamab. Eleven patients already had surgery the remainder patients will have surgery by Oct 30, 2023. Four (36%) had pCR, 3 RCB1 (28%) and 4 RCB2 (36%). Treatment was tolerated well. There were no grade 3 or 4 toxicities. One patient had minor infusion related reaction and grade 2 acne, and 2 grade 2 diarrhea. Conclusions: Neoadjuvant zanidatamab demonstrates significant preliminary efficacy, (pCR/RCB-1 64%) with a good safety profile in patients with stage I node negative HER2+ BC. An update of efficacy and safety of all patients will be presented at the time of meeting Citation Format: Vicente Valero, Jason Mouabbi, Heather Alonzo, Paula Pohlmann, Adaeze Lheme, Amy Hassan, Rashmi Murthy, Xuelin Huang, Wei Qiao, Miral Patel, Gaiane Rauch, Cristina Checka, W. Fraser Symmans, Kelly Hunt, Debu Tripathy, Funda Meric-Bernstam. Neoadjuvant zanidatamab for stage I node negative HER2 positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS09-03.