Patritumab deruxtecan (HER3-DXd) is an antibody-drug coupling (ADC) targeting HER3 consisting of a fully humanized anti-HER3 IgG1 monoclonal antibody linked via a cleavable tetrapeptide linker to a topoisomerase I inhibitor payload (an ezetiocan derivative, DXd) for the study of non-small cell lung cancer (NSCLC).

Patritumab deruxtecan is an investigational HER3-directed antibody-drug conjugate composed of a human immunoglobulin G1 monoclonal antibody (patritumab) directed against HER3 covalently linked to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. Upon binding to HER3, HER3-DXd translocates to lysosomes, where the linker is cleaved by lysosomal enzymes that are upregulated in tumor cells. The cytotoxic payload is then free to enter the nucleus, leading to cell death and, because the payload is membrane permeable, has potential bystander antitumor effects. [1]