Abstract CT212: Combining pembrolizumab with locally delivered radiation therapy for the treatment of metastatic esophageal cancer
Authors: Park Haeseong , Johanns Tanner M. , Lockhart A. Craig , Bradley Jeffrey , Roach Michael , Vlacich Gregory , Amin Manik , Suresh Rama , Bagegni Nusayba , Robinson Clifford G. 
Published: August 2019

Abstract
BACKGROUND Intraluminal brachytherapy for advanced esophageal cancer allows durable control of tumor-related obstructive symptoms by safely delivering large local doses of radiation over just one or a few sessions. Localized, intense doses of hypofractionated radiotherapy elicits more effective anti-tumor immune response than standard doses. In addition, abscopal effect of radiation in distant metastases may be augmented by addition of immune checkpoint inhibitor. Pembrolizumab is approved for treatment of PD-L1 positive gastroesophageal cancer. We therefore propose to evaluate the combination of brachytherapy and pembrolizumab in patients with advanced esophageal cancer. Correlative studies of this study aim to identify predictive biomarkers of response and to characterize the immune response before and after brachytherapy and pembrolizumab to assess immunologic parameters associated with the abscopal effect.
METHODS This is a single institution, open-label, single-dose-level phase I study combining hypofractionated brachytherapy with standard dose pembrolizumab. Primary objective of this trial is to determine the tolerability of localized esophageal hypofractionated brachytherapy administered in two fractions when combined with pembrolizumab in patients with metastatic esophageal cancer. Secondary objective is to assess the antitumor efficacy of the combination. Exploratory objectives are to determine the expression profile of immunologic biomarkers and to annotate the local and distant immune response before and after treatments.Brachytherapy is delivered using a high-dose-rate iridium-192 afterloader via a dedicated esophageal applicator at 16 Gy in 2 fractions, 7-10 days apart. Pembrolizumab is given 1 week after completion of brachytherapy at 200 mg IV every 3 weeks. Endoscopic biopsies are performed before and after brachytherapy, and optionally after 8 weeks on pembrolizumab. Peripheral blood is collected at the same time points, at 3, 6, and 12 months on pembrolizumab, and at the time of progression. Patients with metastatic esophageal cancer who are candidates for brachytherapy for treatment of dysphagia are considered eligible for this trial. Exclusion criteria included prior treatment with PD-(L)1 targeting agent, symptomatic brain metastases, or other contraindication to pembrolizumab, such as active autoimmune disease. We plan to enroll 18 patients which will provide a reasonable ability to detect serious adverse event rates as well as early efficacy signals. There is at least 85% chance of observing at least 1 protocol-specified event if the true rate is 0.1 or greater. We will estimate 95% exact binomial confidence interval of true response rate based on observed responses. 80% of patient accrual is complete as of January 2019. NCT02642809.
Citation Format: Haeseong Park, Tanner M. Johanns, A. Craig Lockhart, Jeffrey Bradley, Michael Roach, Gregory Vlacich, Manik Amin, Rama Suresh, Nusayba Bagegni, Clifford G. Robinson. Combining pembrolizumab with locally delivered radiation therapy for the treatment of metastatic esophageal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT212.