Phase I/II study of high-dose interleukin 2, aldesleukin, in combination with the histone deacetylase inhibitor entinostat in patients with metastatic renal cell carcinoma.

TPS4687 Background: Immunosuppressive factors such as regulatory T cells (Tregs) limit the efficacy of immunotherapies. Histone deacetylase (HDAC) inhibitors have been shown to have anti-tumor activity in different malignancies and to induce immuno-modulatory effects. We have previously reported that a class I specific HDAC inhibitor, entinostat, has synergistic anti-tumor effect in combination with high dose interleukin-2 (IL-2) in a renal cell carcinoma model (Kato Y et al Clinical Cancer Res 2007). Our group has also recently showed that low dose entinostat induces STAT3 acetylation, down-regulates Foxp3 expression in Tregs, and blocks Tregs suppressive function without affecting T effector cells (Shen Li et al PLoSONE 2012). Methods: Based on these preclinical evidences we have initiated a Phase I/II clinical study with entinostat and high dose IL-2 in patients with metastatic renal cell carcinoma. The primary objective of the study is to evaluate the safety, tolerability and efficacy of this combinat...