Syndax Pharmaceuticals, Inc. announced that scientists at Roswell Park Cancer Institute have demonstrated that entinostat, Syndax's novel, oral small molecule inhibitor of class I histone deacetylases, has novel immunomodulatory properties that contribute to the enhanced activity of cancer immunotherapies in models of renal and prostate cancer. The results were published in PLoS ONE in an article titled, "Class I Histone Deacetylase Inhibitor Entinostat Suppresses Regulatory T Cells and Enhances Immunotherapies in Renal and Prostate Cancer Models."
"The results demonstrate a novel immunomodulatory effect of entinostat and provide a rationale for the clinical testing of entinostat to enhance cancer immunotherapy," said Roberto Pili, MD, professor of oncology, chief, genitourinary section and co-leader, genitourinary program, department of medicine, Roswell Park Cancer Institute. "We are interested in testing whether entinostat could improve the benefit seen with immunotherapies in the advanced disease population where oncology treatments are limited."
The results, published in the January 23rd issue of PLOS, show that entinostat inhibits the function of T regulatory cells that are involved in suppressing the anti-tumor activity of immune based therapies. Importantly entinostat maintained the activity of the T effector cell population.
"This exciting pre-clinical data provides new information about entinostat's mechanism of action, expanding the potential for entinostat in new combinations in solid tumors," said Joanna Horobin, MD, president and chief executive officer of Syndax. "Because of collaborations like this one with the Roswell Park Cancer Institute, we are able to continue to investigate new combinations that could ultimately change the clinical outcomes for oncology patients who need new treatment options."
A proof-of-concept clinical study testing this hypothesis is underway with entinostat combined with interleukin-2 in renal cell cancer. Additional studies in combination with recently approved immunotherapies are planned. Entinostat has shown effect in phase 2 clinical testing in other solid tumors including with the aromatase inhibitor exemestane in advanced breast cancer and with the epidermal growth factor receptor inhibitor erlotinib in advanced lung cancer.