A study of using epigenetic modulators to enhance response to pembrolizumab (MK-3475) in microsatellite stable advanced colorectal cancer.

ABSTRACT:

Background

Approximately 95% of advanced colorectal cancer patients (CRC) have mismatch repair MMR-proficient (MMRp) tumors, which do not respond to PD1 blockade alone. Preclinical studies have shown that combined histone deacetylases (HDAC) and/or DNA methyltransferases (DNMT) inhibition can induce susceptibility to immune checkpoint therapy and inhibit tumor growth. We conducted a pilot trial evaluating PD-1 immune checkpoint inhibitor therapy in combination with DNMT and HDAC inhibitors in MMRp CRC. The study was designed with a biological endpoint of change in immune cell infiltration, to determine the optimal epigenetic combination that optimizes the tumor microenvironment. This trial was designed to test that hypothesis.

Results

From January 2016 to November 2018, 27 p

SUBMITTER: Baretti M 

PROVIDER: S-EPMC10149019 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature