Datopotamab deruxtecan, sold under the brand name Datroway, is an anti-cancer medication used for the treatment of breast cancer.
Routes of administration Intravenous
Drug class Antibody-drug conjugate
It is a Trop-2-directed antibody and topoisomerase inhibitor antibody-drug conjugate.
As an antibody-drug conjugate (ADC), datopatomab deruxtecan binds to Trop-2 and undergoes receptor internalization, allowing the payload with the active anti-cancer drug to be transported into the cell.
It is transported into lysosomes.
Inside the cell, it is split by selective cleaving of the tetrapeptide linker by enzymes specific to tumor cells, such as cathepsins.
It results in the release of exatecan, which acts on topoisomerase, an enzyme essential to DNA replication that controls coiling of the DNA helix, leading to DNA damage, cell replication arrest and, consequently, apoptosis.
Then, exatecan is able to penetrate into neighboring cells, thereby causing a cascade of cell death.
The minimum ihibitory concentration (MIC) of exatecan in vitro was shown to be equal to 0.31 μM.
Exatecan is a derivative of camptothecin, a substance found in Camptotheca acuminata.
It is indicated for the treatment of adults with unresectable or metastatic, hormone receptor positive, human epidermal growth factor receptor 2-negative breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
The most common adverse reactions, including laboratory abnormalities, include stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.
Plasma protein binding about 98%.
Half life (t1/2) 4.8 days-5.5 days.
Deruxtecan is metabolized by CYP3A4, without notable glucuronidation.
Moreover, it is a substrate of several transporter systems.
Use with itraconazole (CYP3A inhibitor) and ritonavir (OATP1B/CYP3A inhibitor) is contraindicated.
In the TROPION-Breast01 a multicenter, open-label, randomized trial participants with disease progression, been deemed unsuitable for further endocrine therapy, and have received one or two lines of prior chemotherapy for unresectable or metastatic disease.