Abstract OT2-01-04: Phase IB-II combination neoadjuvant chemotherapy with docetaxel plus atezolizumab plus herceptin SC and pertuzumab (TAHP) for patients with HER2-positive early breast cancer and subsequent atezolizumab plus herceptin SC and pertuzumab (AHP) adjuvant therapy after surgery (Neo-PATH)
Authors: Ahn Hee Kyung , Kim Ji- Yeon , Suh Koung Jin , Kim Gun Min , Sim Sung Hoon , Lee Ki Hyeong , Jung Kyung Hae , Im Seok- Ah , Park Yeon Hee 
Published: March 2020

Abstract
Background Dual HER2-targeting with trastuzumab and pertuzumab combined with cytotoxic chemotherapy as neoadjuvant treatment increased rate of pathologic complete response to 50-65%. Subset of HER2-positive breast cancer has shown adaptive immune infiltrates which was correlated with better prognosis, including whom treated with dual anti-HER2 treatment. Immune checkpoint inhibitor including anti-PD-L1 modulate tumor microenvironment to restore tumor-induced or antibody-treatment induced immunosuppression. Here we investigate an efficacy of combining immunotherapy with anti-HER2 treatment as a neoadjuvant treatment in clinical stage II-III, HER2-positive breast cancer. Trial design This is a Phase Ib-II single arm study of six cycles of neoadjuvant docetaxel, atezolizumab, trastuzumab SC, and pertuzumab combination in patients with HER2-positive breast cancer. After 6 cycles of TAHP, surgery followed by 12 cycles of adjuvant atezolizumab, trastuzumab SC, and pertuzumab(AHP) will be performed. Patients without pCR will receive additional four cycles of doxorubicin and cyclophosphamide between surgery and adjuvant AHP. Eligibility criteria - Locally advanced, inflammatory, or early stage histologically confirmed invasive carcinoma of breast - HER2-positive breast cancer (immunohistochemistry score 3+, or HER2 SISH (or FISH, CISH) positive) - Primary tumor size&gt;2cm or histologically or cytologically confirmed ipsilateral axillary lymph node metastases by fine needle aspiration (clinical stage IIA-IIIC by TNM 7th staging system) - ECOG Performance status 0-1 Specific aims Primary endpoint is a rate of pathologic complete response (pCR) after neoadjuvant docetaxel, atezolizumab, trastuzumab SC, and pertuzumab. Secondary endpoints are comparison of 3-year event free survival rate, disease free survival, and overall survival according to pCR achievement, toxicities, quality of life parameters, biomarker analyses (PD-L1 expression, immune signature, PIK3CA pathway, tumor mutation burden) for pCR and survival, multiomic profiling of tumor tissue using F1CDx. Statistical methods For sample size calculation, we used a Simon’s two-stage optimal design, with a 80 % power and 10% significance. The expected sample size is 60 to test the null hypothesis of pCR rate of ≤ 50% versus the alternative hypothesis of pCR rate of ≥ 65%. Stage 1: If pCR were observed in ≤ 12 patients among the first 23 patients, the alternative hypothesis will be rejected and the study will be discontinued Stage 2: If pCR were observed in ≥ 13 patients among the first 23 patients, additional 37 patients will be accrued (a total of 60 patients). If pCR were observed in &gt; 34 patients, the null hypothesis will be rejected. Considering drop-out rate of 10%, we will accrue 67 patients. Our planned study duration is 42 months (patients accrual 6 months, follow up duration 36 months).
Citation Format: Hee Kyung Ahn, Ji- Yeon Kim, Koung Jin Suh, Gun Min Kim, Sung Hoon Sim, Ki Hyeong Lee, Kyung Hae Jung, Seok- Ah Im, Yeon Hee Park. Phase IB-II combination neoadjuvant chemotherapy with docetaxel plus atezolizumab plus herceptin SC and pertuzumab (TAHP) for patients with HER2-positive early breast cancer and subsequent atezolizumab plus herceptin SC and pertuzumab (AHP) adjuvant therapy after surgery (Neo-PATH) [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 OT2-01-04.