Datopotamab deruxtecan
 | |
| Monoclonal antibody | |
|---|---|
| Type | ? |
| Source | zo |
| Target | Trop-2 |
| Clinical data | |
| Pronunciation | da" toe poe' tah mab der" ux tee' kan |
| Trade names | Datroway |
| Other names | DS-1062a, Dato-DXd, datopotamab deruxtecan-dlnk |
| AHFS/Drugs.com | Multum Consumer Information |
| License data | |
| Routes of administration | Intravenous |
| Drug class | Antibody-drug conjugate |
| ATC code | |
| Legal status | |
| Legal status | |
| Identifiers | |
| CAS Number | |
| DrugBank | |
| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6464H10008N1708O2012S44 |
| Molar mass | 145251.75 g·mol−1 |
Datopotamab deruxtecan, sold under the brand name Datroway, is an anti-cancer medication used for the treatment of breast cancer.[1][2] It is a Trop-2-directed antibody and topoisomerase inhibitor antibody-drug conjugate.[1][2]
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.[2]
Datopotamab deruxtecan was approved for medical use in the United States in January 2025.[2]
Medical uses
[edit]Datopotamab deruxtecan is indicated for the treatment of adults with unresectable or metastatic, hormone receptor positive, human epidermal growth factor receptor 2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.[2]
Side effects
[edit]Datopotamab deruxtecan is associated with a range of adverse events.[3][4]
Pharmacology
[edit]Mechanism of action
[edit]As a antibody-drug conjugate (ADC), datopatomab deruxtecan binds to Trop-2 and undergoes receptor internalization, allowing the payload (i.e., 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 (Gly-Gly-Phe-Gly) 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.[5] Exatecan is a derivative of camptothecin, a substance found in Camptotheca acuminata.[6]
Pharmacodynamics
[edit]| Parameter | Datopatamab deruxtecan | Deruxtecan |
|---|---|---|
| Cmax | 154 μg/mL | 2.8 ng/mL |
| AUC | 671 μg*day/mL | 18 ng*day/mL |
| mean steady state volume | 3.5 | n/d |
| plasma protein binding | n/a | 98% |
| blood-to-plasma concentration ratio | n/d | 0.6 (in vitro) |
| half life (t1/2) | 4.8 days | 5.5 days |
| clearance | 0.6 L/day | n/d |
Metabolism and interactions
[edit]Deruxtecan is metabolised by CYP3A4, whitout notable glucuronidation. Moreover, it is a substrate of several transporter systems, i.e. OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1 and BCRP. Therefore, use with itraconazole (CYP3A inhibitor) and ritonavir (OATP1B/CYP3A inhibitor) is contraindicated.[1]
History
[edit]Efficacy was evaluated in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized trial.[2] Participants must have experienced disease progression, been deemed unsuitable for further endocrine therapy, and have received one or two lines of prior chemotherapy for unresectable or metastatic disease.[2] Participants were excluded for a history of ILD/pneumonitis requiring steroids, ongoing ILD/pneumonitis, clinically active brain metastases, or clinically significant corneal disease.[2] Participants also were excluded for ECOG performance status >1.[2] Randomization was stratified by previous lines of chemotherapy, prior CDK4/6 inhibitor treatment, and geographical region.[2] A total of 732 patients were randomized (1:1) to datopotamab deruxtecan-dlnk (n=365) or investigator's choice of chemotherapy (n=367); eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%).[2]
Society and culture
[edit]Legal status
[edit]Datopotamab deruxtecan was approved for medical use in the United States in January 2025.[2][8] In December 2024, the US Food and Drug Administration granted the application for datopotamab deruxtecan breakthrough therapy designation.[9]
In January 2025, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Datroway, intended for the treatment of breast cancer.[10] The applicant for this medicinal product is Daiichi Sankyo Europe GmbH.[10]
Names
[edit]Datopotamab deruxtecan is the international nonproprietary name,[11] and the United States Adopted Name.[12]
Datopotamab deruxtecan is sold under the brand name Datroway.[1]
References
[edit]- ^ a b c d e f https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761394s000lbl.pdf
- ^ a b c d e f g h i j k l "FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer". U.S. Food and Drug Administration (FDA). 17 January 2025. Retrieved 19 January 2025.
This article incorporates text from this source, which is in the public domain.
- ^ Heist RS, Sands J, Bardia A, Shimizu T, Lisberg A, Krop I, et al. (April 2024). "Clinical management, monitoring, and prophylaxis of adverse events of special interest associated with datopotamab deruxtecan". Cancer Treatment Reviews. 125: 102720. doi:10.1016/j.ctrv.2024.102720. PMID 38502995.
- ^ Gadaleta-Caldarola G, Lanotte L, Infusino S, Gadaleta-Caldarola A, Schipilliti FM, Citrigno C, et al. (2023). "Safety evaluation of Datopotamab deruxtecan for triple-negative breast cancer: a meta-analysis". Cancer Treatment and Research Communications. 37: 100775. doi:10.1016/j.ctarc.2023.100775. PMID 37956525.
- ^ Ogitani Y, Aida T, Hagihara K, Yamaguchi J, Ishii C, Harada N, et al. (15 October 2016). "DS-8201a, A Novel HER2-Targeting ADC with a Novel DNA Topoisomerase I Inhibitor, Demonstrates a Promising Antitumor Efficacy with Differentiation from T-DM1". Clinical Cancer Research. 22 (20): 5097–5108. doi:10.1158/1078-0432.CCR-15-2822. ISSN 1078-0432.
- ^ Govindachari T, Viswanathan N (January 1972). "Alkaloids of Mappia foetida". Phytochemistry. 11 (12): 3529–3531. doi:10.1016/S0031-9422(00)89852-0.
- ^ Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, et al. (November 2017). "Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody–drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: a phase 1 dose-escalation study". The Lancet Oncology. 18 (11): 1512–1522. doi:10.1016/S1470-2045(17)30604-6.
- ^ "Datroway Approved in the U.S. for Patients with Previously Treated Metastatic HR Positive, HER2 Negative Breast Cancer". Daiichi Sankyo US (Press release). 17 January 2025. Retrieved 19 January 2025.
- ^ "Datopotamab deruxtecan granted breakthrough therapy designation in US for patients with previously treated advanced EGFR-mutated non-small cell lung cancer". AstraZeneca US (Press release). 9 December 2024. Retrieved 20 January 2025.
- ^ a b "Datroway EPAR". European Medicines Agency (EMA). 30 January 2025. Retrieved 16 February 2025. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ^ World Health Organization (2020). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 84". WHO Drug Information. 34 (3). hdl:10665/340680.
- ^ "Datopotamab deruxtecan". American Medical Association. Retrieved 20 January 2025.
External links
[edit]- "Datopotamab Deruxtecan (Code C151967)". NCI Thesaurus.
- Clinical trial number NCT05104866 for "A Phase-3, Open-Label, Randomized Study of Dato-DXd Versus Investigator's Choice of Chemotherapy (ICC) in Participants With Inoperable or Metastatic HR-Positive, HER2-Negative Breast Cancer Who Have Been Treated With One or Two Prior Lines of Systemic Chemotherapy (TROPION-Breast01)" at ClinicalTrials.gov
