Tisotumab vedotin, sold under the brand name Tivdak, is an antibody-drug conjugate used to treat cervical cancer.[1] It is a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. It is administered by infusion into a vein.[1]
 | |
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | Tissue factor (TF) |
| Clinical data | |
| Trade names | Tivdak |
| Other names | Tisotumab vedotin-tftv |
| License data | |
| Pregnancy category |
|
| Routes of administration | Intravenous |
| Drug class | Antineoplastic |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | 68–82% (MMAE) |
| Metabolism | Liver, by CYP3A4 (MMAE) |
| Metabolites | MMAE |
| Elimination half-life | 4 days |
| Excretion | Fecal, renal (MMAE) |
| Identifiers | |
| CAS Number | |
| UNII | |
| KEGG | |
Tisotumab vedotin was approved for medical use in the United States in September 2021.[1][3] The U.S. Food and Drug Administration considers it to be a first-in-class medication.[4]
Adverse effects
editIn the United States, Tivdak carries a black box warning for ocular toxicity, which occurs in up to 60% of treated patients.[1] In clinical trials, the most common forms of ocular toxicity were dry eye, conjunctivitis, corneal damage, and blepharitis.[1]
Other common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed) and peripheral neuropathy (42% of patients).[1] Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs.[1]
Mechanism of action
editThe antibody portion of tisotumab vedotin (tisotumab) binds to and forms a complex with tissue factor, a molecule expressed on the surface of cancer cells. This complex is then taken up into the cell, where tisotumab vedotin is broken down by proteolytic cleavage, releasing MMAE, which stops the cell cycle and kills the cell by apoptosis.[1]
History
editTisotumab vedotin was developed by Genmab in Utrecht, the Netherlands, and Copenhagen, Denmark, with the code name TF-011-MMAE.[5] In September 2021, tisotumab vedotin was granted accelerated approval by United States Food and Drug Administration for the use of recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.[6]
Society and culture
editLegal status
editIn April 2024, Tisotumab vedotin was granted traditional approval for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.[7] Tisotumab vedotin previously received accelerated approval for this indication.[7]
Names
editTisotumab vedotin is the international nonproprietary name.[8] Tivdak is the brand name for tisotumab vedotin in the United States.[3]
References
edit- ^ a b c d e f g h i j "Tivdak- tisotumab vedotin injection, powder, for solution". DailyMed. Retrieved 31 October 2021.
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
- ^ a b "Seagen and Genmab Announce FDA Accelerated Approval for Tivdak (tisotumab vedotin-tftv) in Previously Treated Recurrent or Metastatic Cervical Cancer". Seagen. 20 September 2021. Retrieved 20 September 2021 – via Business Wire.
- ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. This article incorporates text from this source, which is in the public domain.
- ^ Breij EC, de Goeij BE, Verploegen S, Schuurhuis DH, Amirkhosravi A, Francis J, et al. (February 2014). "An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors". Cancer Res. 74 (4): 1214–26. doi:10.1158/0008-5472.CAN-13-2440. PMID 24371232. S2CID 10230916.
- ^ Research, Center for Drug Evaluation and (22 September 2021). "FDA grants accelerated approval to tisotumab vedotin-tftv for recurrent or metastatic cervical cancer". FDA.
- ^ a b "FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer". U.S. Food and Drug Administration. 29 April 2024. Retrieved 29 April 2024. This article incorporates text from this source, which is in the public domain.
- ^ World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1): 159–60. hdl:10665/331046.
External links
edit- "Tisotumab vedotin". Drug Information Portal. U.S. National Library of Medicine.
- Clinical trial number NCT03438396 for "A Trial of Tisotumab Vedotin in Cervical Cancer" at ClinicalTrials.gov
- Clinical trial number NCT03245736 for "Tisotumab Vedotin Continued Treatment in Patients With Solid Tumors" at ClinicalTrials.gov
- Clinical trial number NCT02001623 for "Tisotumab Vedotin (HuMax-TF-ADC) Safety Study in Patients With Solid Tumors" at ClinicalTrials.gov
- Clinical trial number NCT02552121 for "Tisotumab Vedotin (HuMax-TF-ADC) Safety Study in Patients With Solid Tumors" at ClinicalTrials.gov
