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This is a combination therapy consisting of three agents: entinostat, a selective class I histone deacetylase inhibitor; ipilimumab, a monoclonal antibody targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4); and nivolumab, a monoclonal antibody targeting programmed cell death protein 1 (PD1). Entinostat acts as an epigenetic modulator that can alter the tumor microenvironment by reducing immunosuppressive myeloid-derived suppressor cells and regulatory T cells, thereby enhancing immune responses. Nivolumab and ipilimumab are immune checkpoint inhibitors that release inhibitory signals on T cells to promote anti-tumor immunity. This combination has been investigated in phase I/II clinical trials for advanced solid tumors including HER2-negative breast cancer and metastatic renal cell carcinoma, particularly in patients who have progressed on prior immunotherapy regimens. The regimen aims to improve response rates by priming the immune system with epigenetic modulation before dual checkpoint blockade[1][2][3][4][5].
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