CGX1321 + pembrolizumab

CGX1321 + pembrolizumab is a **combination therapy** used in investigational oncology trials, primarily for advanced solid tumors and colorectal cancer. **CGX1321** is a selective small molecule inhibitor of *Porcupine* (PORCN), a membrane-bound O-acyltransferase essential for the secretion of WNT ligands, thereby disrupting WNT signaling—a pathway often implicated in tumorigenesis and immune evasion. **Pembrolizumab** is a monoclonal antibody that inhibits the programmed cell death protein 1 (**PD-1**) on T cells, blocking immune checkpoint signaling to enhance anti-tumor immune responses. The combination targets tumor cell proliferation via WNT blockade and simultaneously reverses cancer immune suppression to augment immunotherapy response. This regimen is under Phase 1/1b clinical investigation for **microsatellite-stable colorectal cancer** and other GI malignancies with RSPO fusions or RNF43 inactivating mutations[1][2][3][4][5][6].