KM257 + irinotecan

KM257 + irinotecan is an investigational combination therapy comprising KM257, a humanized monoclonal antibody, and the cytotoxic chemotherapy agent irinotecan. KM257 specifically targets the C-terminal subunit of Mucin 1 (MUC1-C), a transmembrane protein that is frequently overexpressed and aberrantly glycosylated in various epithelial malignancies, including colorectal, pancreatic, and lung cancers. MUC1-C plays a critical role in promoting oncogenic signaling pathways (such as Wnt/β-catenin and NF-κB), driving the epithelial-mesenchymal transition (EMT), and conferring resistance to DNA-damaging agents. By binding to the extracellular domain of MUC1-C, KM257 inhibits these pro-survival signals and may facilitate antibody-dependent cellular cytotoxicity (ADCC). Irinotecan, a topoisomerase I inhibitor, induces lethal DNA damage by preventing the ligation of single-strand DNA breaks. The combination is designed to exploit the synergy between MUC1-C inhibition and topoisomerase I inhibition, potentially sensitizing MUC1-overexpressing tumor cells to irinotecan-induced apoptosis and overcoming chemoresistance.

Other names

K-Mab 257 + irinotecan