Datopotamab deruxtecan

DB16410ApprovedInvestigationalProtein Based Therapies

Datopotamab deruxtecan is a TROP2-directed antibody-drug conjugate with a topoisomerase I inhibitor payload for first-line triple-negative breast cancer not eligible for PD-1/PD-L1 inhibitors, previously treated HR-positive, HER2-negative breast cancer, and EGFR-mutated NSCLC. Datopotamab deruxtecan is a TROP2-directed antibody-drug conjugate that links a humanized anti-TROP2 IgG1 monoclonal antibody to DXd, a topoisomerase I inhibitor, through a cleavable linker.

Mechanism: Datopotamab deruxtecan is an antibody-drug conjugate comprising three main components: datopotamab, DXd, and a cleavable linker between the two. Datopotamab is a monoclonal antibody directed against tumor-associated antigen (TAA) trophoblast cell surface protein 2 (Trop-2), which is a transmembrane protein overexpressed in various tumors with low and/or restricted expression in normal healthy tissues. Datopotamab binds to Trop-2 on the surface of tumor cells, after which the antibody-drug conjugate undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon its release, DXd - a cytotoxic DNA topoisomerase I inhibitor - targets and binds to DNA topoisomerase I, thereby stabilizing the cleavable complex between topoisomerase I and DNA, resulting in DNA breaks, inhibition of DNA replication, and apoptosis.
Curator reviewed · 3 references
Primary indication: United States Datopotamab deruxtecan is indicated for the treatment of adult patients with: - unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast...Curator reviewed · 10 structured indications
First approval: United States, 2025 · European Union, 2025
Also known as: Datopotamab deruxtecan-dlnk · Datopotamab-deruxtecan
Code names: DATO-DXD · DS-1062 · DS-1062a
Brand names: Datroway