Entinostat In Combination With Nivolumab For Patients With Advanced Cholangiocarcinoma And Pancreatic Adenocarcinoma.

TPS4151 Background: The use of antibody therapy targeting immune checkpoints has become a major focus of cancer immunotherapy, with the most compelling activity seen in the minority of patients with immunogenic tumors, where T cell infiltration naturally occurs while most pancreatic cancer (PDAC) and cholangiocarcinoma (CC) are not highly immunogenic, due to an immunosuppressive microenvironment and lack of tumor antigen expression and recognition. Our laboratory has explored entinostat, a histone deacetylase inhibitor (HDACi) to alter the function of suppressive myeloid derived suppressor cells (MDSC) in favor of recruiting T cells in murine PDAC models, showing that entinostat improves survival when given with anti-PD1 therapy. Our efforts are focused on producing new treatment options for CC and PDAC patients using epigenetic and immunotherapy combinations. Methods: An open-label, two-arm study enrolling patients with histologically confirmed unresectable or metastatic CC or PDAC, who have progressed after at least one line of prior therapy. Eligibility criteria include having measurable disease, performance status ≤1, and good end organ function. Exclusion criteria include history of autoimmune disease. Patients have a pre-treatment biopsy followed by 14 days of entinostat at a dose of 5 mg oral once a week followed by a second biopsy. Patients then begin nivolumab 240 mg every two weeks combined with entinostat until disease progression. The study is planned with 27 evaluable subjects per histology based on a Simon’s two-stage design that allows early termination for lack of efficacy. The primary objective of the trial is to determine whether the combination of entinostat plus nivolumab yields a clinically compelling antitumor activity measured as objective response rate (ORR, assessed by RECIST 1.1). Secondary objectives will include progression free survival (PFS), overall survival (OS), safety and immunological correlates to evaluate the effect of HDAC inhibition on the TME by interrogating clinical specimens. The clinical study has been activated in November 2017 (NCT03250273) and 10 of planned 54 patients have been enrolled. Clinical trial information: NCT03250273.