Tisotumab vedotin
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.
| 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 |
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| Routes of administration | Intravenous |
| Drug class | Antineoplastic |
| ATC code |
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| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Protein binding | 68–82% (MMAE) |
| Metabolism | Hepatic, by CYP3A4 (MMAE) |
| Metabolites | MMAE |
| Elimination half-life | 4 days |
| Excretion | Fecal, renal (MMAE) |
| Identifiers | |
| CAS Number | |
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| KEGG | |
Tisotumab vedotin was approved for medical use in the United States in September 2021.[1][2] It is administered by infusion into a vein every 3 weeks.[1]
Tisotumab vedotin is the international nonproprietary name (INN).[3]
Adverse effects
In 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]
To prevent eye damage, premedication with three different types of eye drops—a topical corticosteroid, a vasoconstrictor, and artificial tears—is recommended before each infusion, as well as the use of cold packs over the eyes.[1]
Other very 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
The 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
Tisotumab was developed by Genmab in Utrecht, the Netherlands, and Copenhagen, Denmark, with the code name TF-011-MMAE.[4] It is marketed in a 50/50 partnership between Genmab and Seagen, which developed and owns the intellectual property for vedotin technology (monoclonal antibody–MMAE conjugates).
References
- "Tivdak- tisotumab vedotin injection, powder, for solution". DailyMed. Retrieved 31 October 2021.
- "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.
- 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.
- Breij EC, de Goeij BE, Verploegen S, Schuurhuis DH, Amirkhosravi A, Francis J, Miller VB, Houtkamp M, Bleeker WK, Satijn D, Parren PW (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.
External links
- "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