Epidermal growth factor receptor and Mesenchymal-epithelial transition tyrosine kinase receptor (EGFR and c-MET)

AZD9592 is a first-in-class bispecific antibody-drug conjugate designed to target both EGFR and c-MET, key receptor tyrosine kinases involved in oncogenic signaling, tumor cell proliferation, survival, and therapy resistance. By internalizing into tumor cells that express these receptors—and especially targeting cells with high c-MET expression to minimize EGFR-driven toxicity—AZD9592 releases a cytotoxic topoisomerase I inhibitor payload, leading to double-strand DNA breaks and cell death. It is under clinical evaluation for use in advanced solid tumors, notably in non-small cell lung cancer and colorectal cancer with EGFR and c-MET involvement, and is of particular interest for overcoming acquired resistance to EGFR-targeted therapies like osimertinib[2][3][4][6][1].

Other names

ErbB-1HER1Epidermal growth factor receptorMETHepatocyte growth factor receptorMesenchymal-epithelial transition factor

Bispecific antibody binding to EGFR and c-MET, leading to ADC internalization Lysosomal processing releases proprietary topoisomerase 1 inhibitor payload (TOP1i: AZ14170132) Induction of DNA double strand breaks, activating DNA damage response, triggering apoptotic cell death