Abstract OT1-02-02: A phase II study of pembrolizumab in combination with palliative radiotherapy for metastatic hormone receptor positive breast cancer

BACKGROUND: Despite recent advances in the treatment of patients with metastatic hormone receptor positive (HR+)/HER2- breast cancer (BC), it remains an incurable disease. The activity of immune checkpoint inhibitors (ICI) as monotherapy in patients with metastatic HR+/HER2- BC has been limited. Therefore, the addition of other strategies that elicit an immunogenic tumor microenvironment may be needed. We hypothesize that radiation therapy (RT) will potentiate the efficacy of the PD-1 inhibitor pembrolizumab in patients with metastatic HR+/HER2- BC. METHODS: Trial Design: This is a phase II single arm study assessing objective response rate (ORR) according to RECIST 1.1 in patients with metastatic HR+/HER2- BC who will receive pembrolizumab in combination with palliative RT. Pembrolizumab 200 mg intravenously will be administered 2-7 days before day 1 of RT, and will be given every 21 days until disease progression. Biopsies will be performed in the same lesion at baseline (mandatory if tumor tissue is accessible outside the field of RT) and during cycle 2 within 7-14 days before the day 1 of cycle 3 of pembrolizumab. Key Eligibility Criteria: Patients with metastatic HR+/HER2- BC, with measurable disease outside the field of radiation, for whom palliative RT to at least one bone, lymph node, or soft tissue lesion is indicated. Radiation of visceral lesions (such as lung or hepatic lesions) is not permitted. Although prior RT is allowed, patients must be at least 3 months free from RT; Re-irradiation of the same field is not allowed. There is no limit to the number of previous treatments, and systemic treatment naive patients for metastatic disease are also eligible. Specific Aims: The primary aim is to evaluate the efficacy of the combination, as defined by objective response rate (ORR) outside the field of RT according to RECIST 1.1. Secondary objectives include to determine the ORR according to immune-related criteria, the progression-free survival, the abscopal response rate, the clinical benefit rate, the safety and the tolerability of the combination. In addition, correlative studies will be performed to explore the correlation of immunosuppressive and/or immune-stimulating immune marker profiles at baseline and after cycle 2 to disease response to therapy. Statistical Methods: Using the Simons “optimal” method, in the first stage, 8 patients will be enrolled. If there is at least 1 response, accrual will continue to the second stage where up to 19 additional patients will be enrolled. If at least 3 of these 27 patients have an objective response (≥10%), the regimen will be considered worthy of further study. With this design, the probability of stopping the trial early is 78% if the true response rate is 3%. If the true response rate is 20% the chance that the regimen is declared worthy of further study is 80%. Patient accrual and target accrual: The trial opened in April/2017, and so far, has accrued 2 patients with a target accrual of 27 patients. Accrual should be complete in 14-25 months. Clinical trial information: NCT03051672. Citation Format: Barroso-Sousa R, Gao H, Barry WT, Krop IE, Schoenfeld JD, Tolaney SM. A phase II study of pembrolizumab in combination with palliative radiotherapy for metastatic hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-02.