pexidartinib + pembrolizumab

Pexidartinib + pembrolizumab is a combination therapy under clinical investigation for advanced solid tumors. **Pexidartinib** is an orally bioavailable small molecule tyrosine kinase inhibitor that selectively inhibits colony-stimulating factor-1 receptor (**CSF-1R**), leading to decreased proliferation and survival of tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), thereby reducing immune suppression within the tumor microenvironment. **Pembrolizumab** is a humanized monoclonal antibody targeting the programmed cell death protein 1 (**PD-1**) receptor on T-cells, blocking its interaction with PD-L1 and PD-L2 to restore and potentiate antitumor immune responses. The rationale for the combination is to concurrently suppress two distinct pathways of tumor immune evasion—macrophage-driven suppression (CSF-1R) and T cell checkpoint inhibition (PD-1)—to enhance antitumor activity, particularly in gastrointestinal and other solid tumors[1][2][4].

Other names

pexidartinib and pembrolizumab