drug_type
RELEVANT_DRUG
intervention_type
Antibody-drug conjugate (ADC)
drug_description
A HER2-targeted antibody-drug conjugate consisting of a humanized anti-HER2 IgG1 (trastuzumab) linked to a topoisomerase I inhibitor payload (deruxtecan); binds HER2 (including low expressers), is internalized, releases the payload to inhibit Topo I causing DNA damage and apoptosis, with a membrane-permeable bystander effect; the antibody can also mediate ADCC.
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-targeted ADC: trastuzumab binds HER2 on tumor cells (including low expressers), is internalized, and releases the topoisomerase I inhibitor deruxtecan (DXd), causing DNA damage, replication arrest, and apoptosis; the membrane-permeable payload enables bystander killing, and the IgG1 Fc can mediate ADCC.
drug_name
Trastuzumab deruxtecan
nct_id_drug_ref
NCT05795101