ENCORE 601: A phase 2 study of entinostat in combination with pembrolizumab in patients with microsatellite stable metastatic colorectal cancer.

3557Background: In studies reported to date, no objective responses have been observed with PD-1 inhibitors in advanced/metastatic CRC (mCRC) pts with microsatellite stable (MSS)/mismatch repair proficient (pMMR) tumors. About 95% of mCRC pts have this phenotype; additional strategies are needed to improve effectiveness of immunotherapies in these pts. Entinostat (ENT), an oral, class I-selective histone deacetylase inhibitor, enhances anti-PD-1 activity by downregulation of immunosuppressive cell types in the tumor microenvironment in vivo and has shown promising activity with pembrolizumab (PEMBRO) in pts with melanoma and lung cancer. This study evaluates the safety and efficacy of ENT + PEMBRO in MSS/pMMR CRC pts. Methods: This study is a multi-cohort, Simon 2-stage, phase II trial. Main eligibility criteria for pts in the CRC cohort are: documented MSS/pMMR status, ≥1 prior regimen in the metastatic setting, and no prior anti-PD-(L)1 therapy. All pts received ENT 5 mg PO QW + PEMBRO 200 mg IV Q3W. Th...