Abstract OT1-01-06: A pilot study utilizing a HER2 directed dendritic cell vaccine during neoadjuvant therapy of HER2+ breast cancer

Abstract

Abstract Background: During the natural progression of early breast cancer, it has been demonstrated that the protective host immune response against HER2 is lost early on. Using a type 1 dendritic cell (DC1) vaccine loaded with HER2 peptides has been shown to be effective in restoring anti HER2 immune responsiveness and can lead to regression of very early non-invasive breast cancers. Prior investigations conducted by our group has suggested DC vaccines may sensitize cancers to subsequent systemic chemotherapy, and the Geparnuevo trial also suggested a prechemotherapy dosing with checkpoint therapy may improve pathologic complete response (pCR) rates in TNBC. We launched a pilot study to demonstrate safety, feasibility, and preliminary efficacy of administering the DC1 HER2 vaccine for 3 weeks prior to the initiation of neoadjuvant systemic therapy for stage II-III ER-HER2+ breast cancer. Methods: This single site study is a pilot design with a safety run in phase (n = 12) followed by an expansion cohort of 18 patients. Patients with stage II-III ER-HER2+ breast cancer who are eligible to receive neoadjuvant HER2 based chemotherapy (TCHP) can enroll. The safety run in evaluates two schedules of DC1 vaccination (ARM A = once weekly x 3 weeks and ARM B = twice weekly x 3 weeks) and will enroll six patients in each arm. After the first 3 weeks of DC1 neoadjuvant chemotherapy will be administered using standard docetaxel, carboplatin, trastuzumab, and pertuzumab given intravenously once every 3 weeks for 6 cycles. Booster vaccines will be given at weeks 25, 56, 80, and 104 and immune monitoring will be performed at these timepoints. The safety run in will evaluate safety using CTCAE 4.03 criteria along with the immunogenicity of each arm measured by ELISPOT. The arm with the best immune response at 3 weeks will be selected to proceed forward during the expansion cohort using an endpoint of pCR. Secondary endpoints will be recurrence free survival rate at 3 years and immune response. The pilot design is hypothesis generating but is likely able to detect a significant difference in pCR if the true rate is 75% assuming a historical rate of 55%. Accrual to the safety run in phase is complete and the expansion phase is underway using the twice weekly vaccination schedule. Citation Format: Hatem Soliman, Deanna Hogue, Hyo Han, Hung Khong, Ricardo Costa, Avan Armaghani, Axia Soyano Muller, Nazanin Khakpour, Marie C Lee, John Kiluk, Brian Czerniecki. A pilot study utilizing a HER2 directed dendritic cell vaccine during neoadjuvant therapy of HER2+ breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT1-01-06.