Abstract OT1-17-02: A phase II study of pembrolizumab plus fulvestrant in hormone receptor positive, HER-2 negative advanced/metastatic breast cancer patients
Authors: Chan Nancy , Moore Dirk , Tandra Pavankumar , Rana Jatin , Omene Coral , George Mridula , Krishnamurthy Jairam , Desai Shruti , Patel Nayana , Wang Yue , Bicomong Marc , Tan Xiao-wei , Hirshfield Kim , Ganesan Shridar , Toppmeyer Deborah 
Published: March 2022

Abstract
Background:ER positive, HER2-negative breast cancer is the most common subtype in both early and late stages. Previous studies have demonstrated a subset of patients may derive benefit from immune check point inhibitors in combination with endocrine therapy. We hypothesize that Pembrolizumab in combination with fulvestrant will demonstrate anti-tumor activity measured by frequency of response. Trial Design: This is a non-randomized, multi-site, open-label Phase II trial for subjects with metastatic, hormone receptor positive, HER2 negative breast cancer. The study will enroll 47 patients to evaluate the anti-tumor activity of pembrolizumab with fulvestrant as measured by RECIST 1.1 and irRECIST tumor response and by progression free survival. (ClinicalTrials.gov Identifier: NCT03393845) Eligibility Criteria: Patients with advanced non-resectable/metastatic breast cancer that is estrogen receptor positive (ER+) and/or (PR+), HER2 negative (HER2-), with no more than two lines of prior hormonal therapy or no more than two lines of prior chemotherapy. Specific aims: To evaluate the overall response rate (ORR) of pembrolizumab plus fulvestrant in patients with hormone receptor positive, HER2 negative advanced/metastatic breast cancer. Secondary aims include safety and tolerability of the combination. Tumor genomic profiling on solid and/or liquid specimens using next generation sequencing assays to help identify biomarkers of response to immunotherapy. Statistical Methods: This is a phase II study that will enroll a total of 47 patients to evaluate the anti-tumor activity of pembrolizumab with fulvestrant as measured by RECIST 1.1 tumor response and by progression free survival in patients with breast cancer. For maximal 47 patients, 21 will be accrued during stage I and 26 during stage II. If 6 or fewer responses are observed during stage I, then the trial is stopped early for futility. If there are 7 or more responses during stage I, the trial will go on to stage II, in which an additional 26 patients will be accrued. If a total of 21 or more responses are observed by the end of stage II, then the trial will be considered successful, and the combination therapy considered worthy of further investigation. Present accrual and target accrual: The study is currently enrolling patients at Rutgers Cancer Institute of New Jersey, Michigan State University, and University of Nebraska. 20 of 47 patients have been enrolled on study to date.
Citation Format: Nancy Chan, Dirk Moore, Pavankumar Tandra, Jatin Rana, Coral Omene, Mridula George, Jairam Krishnamurthy, Shruti Desai, Nayana Patel, Yue Wang, Marc Bicomong, Xiao-wei Tan, Kim Hirshfield, Shridar Ganesan, Deborah Toppmeyer. A phase II study of pembrolizumab plus fulvestrant in hormone receptor positive, HER-2 negative advanced/metastatic breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-17-02.