Tisotumab vedotin

Tisotumab vedotin

Monoclonal antibody
Type	Whole antibody
Source	Human
Target	Tissue factor (TF)
Names
Trade names	Tivdak
Other names	Tisotumab vedotin-tftv
Clinical data
Drug class	Antineoplastic
Main uses	Cervical cancer
Side effects	Tiredness, nausea, peripheral neuropathy, hair loss, nose bleeds, kidney problems, eye problems, diarrhea, rash
Pregnancy category	Contraindicated
Routes of use	Intravenous
External links
AHFS/Drugs.com	Monograph
Legal
License data	US DailyMed: Tisotumab_vedotin
Legal status	US: ℞-only
Pharmacokinetics
Protein binding	68–82% (MMAE)
Metabolism	Liver, by CYP3A4 (MMAE)
Metabolites	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.

Medical use

Dosage

It is given as 2 mg/kg, up to a dose of 200 mg, over half an hour every three weeks.

Side effects

In the United States, it carries a black box warning for eye problems, which occurs in up to 60% of people. The most common forms were dry eye, conjunctivitis, corneal damage, and blepharitis.

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

Mechanism of action of Tisotumab vedotin

See also: Antibody-drug conjugate

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.

History

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).

External links

Identifiers:	ATC code: None CAS Number: 1418731-10-8 UNII: T41737F88A KEGG: D11814

• "Tisotumab vedotin". Drug Information Portal. U.S. National Library of Medicine. Archived from the original on 2022-01-27. Retrieved 2022-10-17. {{cite web}}: More than one of |archivedate= and |archive-date= specified (help); More than one of |archiveurl= and |archive-url= specified (help)
• 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