Definition

An antibody-drug conjugate (ADC) composed of an immunoglobulin G1 (IgG1) human monoclonal antibody directed against human epidermal growth factor receptor 3 (HER3; ErbB3) conjugated via a cleavable peptide linker to a cytotoxic DNA topoisomerase I inhibitor, with potential antineoplastic activity. Upon administration of anti-HER3 ADC SHR-A2009, the anti-HER3 antibody moiety targets and binds to HER3 expressed on tumor cells. Upon binding, internalization and linker cleavage, the topoisomerase I inhibitor targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA and resulting in DNA breaks, inhibition of DNA replication and apoptosis in HER3-expressing tumor cells. HER3, a member of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases, is frequently overexpressed in tumors.