Trastuzumab deruxtecan (Enhertu)

General information

Class/mechanism from the NCI Drug Dictionary: An antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting human epidermal growth factor receptor 2 (ERBB2; EGFR2; HER2) conjugated to a derivative of the camptothecin analog exatecan (DXd; DX-8951 derivative), a DNA topoisomerase 1 (topoisomerase I; Top1) inhibitor, with potential antineoplastic activity. Upon administration of anti-HER2 ADC conjugate DS-8201a, the antibody moiety targets and binds to HER2 on tumor cells. Upon antibody/antigen binding and internalization, the DX-8951 derivative moiety 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, DS-8201a induces antibody-dependent cell-mediated cytotoxicity (ADCC) and causes a bystander killing effect, thereby killing neighboring HER2-expressing tumor cells.
Route: IV

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Diseases for which it is used

History of changes in FDA indication

Breast cancer

12/20/2019: Granted accelerated approval for patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

Gastric cancer

1/15/2021: Approved for adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen.

Also known as

Code name: DS-8201a
Generic name: fam-trastuzumab deruxtecan-nxki
Brand name: Enhertu