|Target||Tissue factor (TF)|
|Other names||Tisotumab vedotin-tftv|
|Main uses||Cervical cancer|
|Side effects||Tiredness, nausea, peripheral neuropathy, hair loss, nose bleeds, kidney problems, eye problems, diarrhea, rash|
|US NLM||Tisotumab vedotin|
|Protein binding||68–82% (MMAE)|
|Metabolism||Liver, by CYP3A4 (MMAE)|
|Elimination half-life||4 days|
|Excretion||Fecal, renal (MMAE)|
Tisotumab vedotin, sold under the brand name Tivdak, is a medication used to treat cervical cancer. It is used when other treatments are not effective. It is given by gradual injection into a vein every 3 weeks.
Common side effects include tiredness, nausea, peripheral neuropathy, hair loss, nose bleeds, kidney problems, eye problems, diarrhea, and rash. Other side effects may include pneumonitis. Use in pregnancy may harm the baby. It is an antibody-drug conjugate, a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), an inhibitor of cell division.
Tisotumab vedotin was approved for medical use in the United States in 2021. As of 2022 it is not approved in Europe or the United Kingdom. In the United States a dose of 120 mg costs about 19,300 USD as of 2022.
It is given as 2 mg/kg, up to a dose of 200 mg, over half an hour every three weeks.
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.
Other very common adverse effects include bleeding (occurring in approximately 60% of patients, most often nosebleed) and peripheral neuropathy (42% of patients). Like all drugs containing MMAE, tisotumab vedotin can cause inflammation of the lungs.
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.
Tisotumab was developed by Genmab in Utrecht, the Netherlands, and Copenhagen, Denmark, with the code name TF-011-MMAE. 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).
Tisotumab vedotin is the international nonproprietary name (INN).
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- 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.
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- 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