drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
HER2-directed antibody–drug conjugate (IgG1 trastuzumab linked via a cleavable linker to the deruxtecan [DXd] topoisomerase I inhibitor). Binds HER2, internalizes, releases DXd in lysosomes to inhibit TOP1 causing DNA damage; trastuzumab component can inhibit HER2 signaling and mediate ADCC; payload can exert a bystander effect.
nci_thesaurus_concept_id
C128799
nci_thesaurus_preferred_term
Trastuzumab Deruxtecan
nci_thesaurus_definition
An antibody-drug conjugate (ADC) composed of trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to deruxtecan, a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with antineoplastic activity. Upon administration of trastuzumab deruxtecan, trastuzumab targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, deruxtecan binds to and inhibits Top1-DNA complexes, which results in an inhibition of DNA replication, cell cycle arrest and tumor cell apoptosis. HER2, a tyrosine kinase receptor, is overexpressed by many cancer cell types. In addition, trastuzumab deruxtecan induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect.
drug_mesh_term
Trastuzumab Deruxtecan
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
HER2-directed antibody-drug conjugate: trastuzumab (IgG1) linked via a cleavable linker to deruxtecan (DXd), a topoisomerase I inhibitor. After HER2 binding and internalization, lysosomal cleavage releases DXd to inhibit TOP1, causing DNA damage and tumor cell death. The trastuzumab component also blocks HER2 signaling and mediates ADCC; the membrane-permeable payload can produce a bystander effect.
drug_name
Trastuzumab Deruxtecan
nct_id_drug_ref
NCT06533826