xevinapant + pembrolizumab

xevinapant + pembrolizumab is an investigational combination therapy being evaluated for the treatment of advanced gastrointestinal malignancies, specifically non-MSI-high (microsatellite stable) pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). Xevinapant (formerly Debio 1143) is an orally available, small-molecule monovalent SMAC (Second Mitochondrial-derived Activator of Caspases) mimetic that acts as an antagonist of Inhibitor of Apoptosis Proteins (IAPs), including cIAP1, cIAP2, and XIAP. By antagonizing these proteins, xevinapant restores apoptotic signaling in tumor cells and promotes a pro-inflammatory microenvironment, potentially sensitizing 'cold' tumors to immunotherapy. Pembrolizumab is a humanized monoclonal antibody that inhibits the programmed cell death protein 1 (PD-1) receptor, preventing its interaction with PD-L1 and PD-L2 to enhance anti-tumor T-cell activity. This combination is being investigated in the CATRIPCA Phase I trial, sponsored by Centre Léon Bérard, to determine if IAP inhibition can overcome intrinsic resistance to immune checkpoint inhibitors in these difficult-to-treat cancer types.

Brand names

Keytruda

Other names

xevinapantpembrolizumab