drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
Antibody–drug conjugate targeting HER2; trastuzumab linked via a cleavable linker to a topoisomerase I inhibitor payload (DXd). Binds HER2, internalizes, releases DXd to induce DNA damage, also blocks HER2 signaling and mediates ADCC with bystander killing.
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 monoclonal antibody (trastuzumab) linked via a cleavable linker to a membrane-permeable topoisomerase I inhibitor payload (DXd). After HER2 binding and internalization, the linker is cleaved to release DXd, which inhibits Top1, causing DNA damage, replication arrest, and apoptosis. The antibody also blocks HER2 signaling and mediates Fc-dependent ADCC, with a bystander killing effect from the released payload.
drug_name
Trastuzumab deruxtecan
nct_id_drug_ref
NCT05993234