patritumab deruxtecan

Patritumab deruxtecan is an investigational, first-in-class antibody-drug conjugate (ADC) targeting the human epidermal growth factor receptor 3 (HER3/ErbB3). It consists of a fully human anti-HER3 IgG1 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload (DXd, an exatecan derivative) via a stable tetrapeptide-based cleavable linker. After binding to HER3 on tumor cells—commonly upregulated in EGFR-mutated non-small cell lung cancer (NSCLC) after resistance to EGFR tyrosine kinase inhibitors—the ADC is internalized and the linker is cleaved by lysosomal enzymes. This releases the cytotoxic payload into the nucleus, causing DNA damage and cell death; due to membrane permeability of DXd, there may also be a bystander effect on neighboring tumor cells. Patritumab deruxtecan was developed for use in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with two or more systemic therapies. The drug was discovered by Daiichi Sankyo and jointly developed with Merck[1][2][4][5][7].

Other names

patritumab deruxtecanU3-1402U-3-1402U 3-1402HER3-DXdHER-3-DXdHER 3-DXd