anti-EGFR/c-Met/TOP1i ADC AZD9592

An antibody-drug conjugate (ADC) composed of a bispecific antibody targeting both epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR; c-Met) and conjugated to a topoisomerase-1 inhibitor (TOP1i), with potential antineoplastic activity. Upon administration, anti-EGFR/c-Met/TOP1i ADC AZD9592 simultaneously targets and binds to the extracellular domains of wild-type (WT) or certain mutant forms of both EGFR and c-Met expressed on cancer cells. Upon binding and internalization, the TOP1i moiety is released, binds to TOP1 and stabilizes cleaved DNA-TOP1 complexes. This prevents DNA re-ligation, induces irreversible DNA strand breaks, prevents DNA repair, and leads to cycle arrest and apoptosis specifically in tumor cells expressing EGFR and c-Met. EGFR and c-Met, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation.