Entinostat plus pembrolizumab shows efficacy in anti-PD-1-resistant melanoma

Source: Healio, March 2019

ATLANTA — The combination of the histone deacetylase inhibitor entinostat and the anti-PD-1 inhibitor pembrolizumab induced clinical responses and appeared well-tolerated among patients with melanoma that progressed on prior anti-PD-1 treatment, according to results from the single-arm ENCORE 601 phase 1b/phase 2 clinical trial presented at American Association of Cancer Research Annual Meeting.

Histone deacetylase (HDAC) inhibitors such as entinostat (SNDX-275, Syndax) may counteract resistance to checkpoint inhibition in two ways: by suppressing regulatory cells — including myeloid-derived suppressor cells and regulatory T cells — and by increasing antigen expression on cancer cells.

“HDAC inhibition has been shown to decrease the function of T-regulatory cells (T-regs) and myeloid-derived suppressor cells, and increase antigen expression in tumors,” Ryan J. Sullivan, MD, assistant professor of hematology and oncology at Massachusetts General Hospital Cancer Center, told HemOnc Today. “A number of PD-1/PD-L1 inhibitor resistance mechanisms have been described and/or proposed and include, although are not limited to, high activity of T-regs, expression of myeloid-derived suppressor cells, and down-modulation of tumor antigen expression. Thus, it seemed logical to combine an agent like entinostat with pembrolizumab in PD-1-resistant/refractory melanoma.”