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Nivolumab + entinostat is an investigational combination therapy consisting of two agents with distinct mechanisms of action. Nivolumab is a monoclonal antibody that targets and inhibits the programmed cell death protein 1 (PD-1) receptor, thereby blocking immune checkpoint signaling and enhancing T-cell mediated antitumor responses. Entinostat is a selective class I histone deacetylase (HDAC) inhibitor that modulates gene expression by altering chromatin structure, leading to reduced immunosuppression in the tumor microenvironment—primarily through depletion of myeloid-derived suppressor cells and increased activation/maturation of dendritic cells. The rationale for combining these agents is to overcome resistance to immune checkpoint inhibitors by reprogramming the tumor microenvironment, making tumors more susceptible to immunotherapy. This combination has been studied primarily in advanced solid tumors such as pancreatic ductal adenocarcinoma, renal cell carcinoma, cholangiocarcinoma, and pediatric high-risk solid/CNS tumors[1][2][3][7][8].
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