Tisotumab vedotin

Monoclonal antibodies for tumors

US DailyMed: Tisotumab vedotin

Pregnancy
category

Contraindicated^[1]

Routes of
administrationIntravenousDrug classAntineoplasticATC code

L01FX23 (WHO)

US: WARNING^[2]Rx-only^[1]

Pharmacokinetic dataProtein binding68–82% (MMAE)MetabolismLiver, by CYP3A4 (MMAE)MetabolitesMMAEElimination half-life4 daysExcretionFecal, renal (MMAE)IdentifiersCAS Number

1418731-10-8

UNII

T41737F88A

KEGG

D11814

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]

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

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]

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

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 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

Legal status

In 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

Tisotumab vedotin is the international nonproprietary name.^[8] Tivdak is the brand name for tisotumab vedotin in the United States.^[3]

References

^ ^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

"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

Targeted cancer therapy / antineoplastic agents (L01)

CI monoclonal antibodies ("-mab")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Cetuximab Panitumumab) HER2/neu (Pertuzumab, Trastuzumab (+hyaluronidase) Trastuzumab emtansine Trastuzumab deruxtecan)
Others for solid tumors	EpCAM (Catumaxomab Edrecolomab) VEGF-A (Bevacizumab)
Leukemia/lymphoma	lymphoid: CD3 (Glofitamab, Elranatamab, Mosunetuzumab), CD20 (Glofitamab Ibritumomab Mosunetuzumab Obinutuzumab Ofatumumab Rituximab Tositumomab), CD30 (Brentuximab), CD52 (Alemtuzumab) myeloid: CD33 (Gemtuzumab ozogamicin)
Other	Amivantamab Atezolizumab Avelumab Belantamab mafodotin Bermekimab Blinatumomab Cemiplimab Daratumumab Dinutuximab beta Dostarlimab Durvalumab Elotuzumab Enfortumab vedotin Epcoritamab Inotuzumab ozogamicin Ipilimumab Isatuximab Loncastuximab tesirine Mirvetuximab soravtansine Mogamulizumab Moxetumomab pasudotox Naxitamab Necitumumab Nivolumab Olaratumab Oportuzumab monatox Pembrolizumab Polatuzumab vedotin Prolgolimab Ramucirumab Retifanlimab Sabatolimab Sacituzumab govitecan Serplulimab Sugemalimab Tafasitamab Talquetamab Tarlatamab Teclistamab Tislelizumab Tisotumab vedotin Toripalimab Tremelimumab

Tyrosine kinase inhibitors ("-nib")

Receptor tyrosine kinase	ErbB: HER1/EGFR (Afatinib Aumolertinib Brigatinib Dacomitinib Erlotinib Gefitinib Icotinib Mobocertinib Olmutinib Osimertinib Rociletinib Vandetanib) HER1/EGFR and HER2/neu Lapatinib Neratinib Tucatinib RTK class III: C-kit and PDGFR (Avapritinib Axitinib Masitinib Pazopanib Ripretinib Sorafenib Sunitinib Toceranib) FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK)) VEGFR Axitinib Cediranib Fruquintinib Lenvatinib Nintedanib Pazopanib Regorafenib Semaxanib Sorafenib Sunitinib Tivozanib Toceranib Vandetanib ALK Alectinib Brigatinib Ceritinib RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR). c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)
Non-receptor	bcr-abl Asciminib Bosutinib Dasatinib Imatinib Nilotinib Ponatinib Radotinib Src (Bosutinib Dasatinib) Janus kinase Baricitinib Fedratinib Filgotinib Lestaurtinib Momelotinib Pacritinib Ruxolitinib MAP2K Binimetinib Cobimetinib Selumetinib Trametinib EML4-ALK Crizotinib Entrectinib Lorlatinib Bruton's Acalabrutinib Ibrutinib Orelabrutinib Pirtobrutinib Zanubrutinib

Receptor tyrosine kinase

HER1/EGFR and HER2/neu

RTK class III: C-kit and PDGFR (Avapritinib
Axitinib
Masitinib
Pazopanib
Ripretinib
Sorafenib
Sunitinib
Toceranib)
FLT3 (Lestaurtinib, Gilteritinib (AXL, ALK, LTK))

VEGFR
- Axitinib
- Cediranib
- Fruquintinib
- Lenvatinib
- Nintedanib
- Pazopanib
- Regorafenib
- Semaxanib
- Sorafenib
- Sunitinib
- Tivozanib
- Toceranib
- Vandetanib

ALK

RET inhibitors: Entrectinib (ALK, ROS1, NTRK), Futibatinib (FGFR2), Infigratinib, Larotrectinib (NTRK), Pemigatinib (FGFR), Pralsetinib, Repotrectinib (ROS1, TRK, ALK), Selpercatinib (VEGFR, FGFR), Vandetanib (VEGFR, EGFR).

c-MET inhibitors: Cabozantinib (VEGFR), Capmatinib, Crizotinib (ALK)

Non-receptor

bcr-abl
- Asciminib
- Bosutinib
- Dasatinib
- Imatinib
- Nilotinib
- Ponatinib
- Radotinib

Src (Bosutinib
Dasatinib)

Janus kinase

MAP2K

EML4-ALK

Bruton's

Other

fusion protein against VEGF (Aflibercept)
proapoptotic peptide against ANXA2 and prohibitin (Adipotide)
exotoxin against IL-2 (Denileukin diftitox)
mTOR inhibitors
- Everolimus
- Ridaforolimus
- Temsirolimus
hedgehog inhibitors
- Glasdegib
- Sonidegib
- Vismodegib
CDK inhibitors
- Abemaciclib
- Dalpiciclib
- Palbociclib
- Ribociclib
- Trilaciclib
KRAS inhibitors
- Adagrasib
- Sotorasib
Pi3K inhibitors
- Alpelisib
- Copanlisib
- Duvelisib
- Idelalisib
- Parsaclisib
Cabozantinib
Capmatinib
Entrectinib
Erdafitinib
Gilteritinib
Larotrectinib
Lenvatinib
Masitinib
Midostaurin
Nintedanib
Odronextamab
Pazopanib
Pemigatinib
Pexidartinib
Quizartinib
Regorafenib
Ripretinib
Sorafenib
Sunitinib
Tebentafusp
Tepotinib
Vandetanib
Venetoclax

Monoclonal antibodies for tumors

Tumor

Human	Adecatumumab^§ Amivantamab Ascrinvacumab^§ Atezolizumab Balstilimab^† Botensilimab Cixutumumab^§ Conatumumab^§ Daratumumab Drozitumab^§ Duligotumab^§ Dusigitumab^§ Enfortumab vedotin Enoticumab^§ Figitumumab^§ Flanvotumab^§ Ganitumab^† Glembatumumab vedotin^† Intetumumab^§ Ipilimumab Iratumumab^§ Istiratumab Icrucumab^§ Lexatumumab^§ Lucatumumab^§ Mapatumumab^§ Narnatumab^§ Necitumumab Nesvacumab^§ Nivolumab^# Ofatumumab Olaratumab^† Panitumumab Patritumab^§ Pembrolizumab^# Pritumumab^§ Radretumab^§ Ramucirumab Rilotumumab^† Robatumumab^§ Seribantumab^§ Sugemalimab Tarextumab^§ Tisotumab vedotin Teprotumumab^† Tovetumab^§ Vantictumab^§ Votumumab^§ Zalutumumab^†
Mouse	Abagovomab Altumomab pentetate Anatumomab mafenatox Arcitumomab Bectumomab Blinatumomab Capromab pendetide Detumomab Edrecolomab Ibritumomab tiuxetan Igovomab Lilotomab Minretumomab Mitumomab Nacolomab tafenatox Moxetumomab pasudotox Naptumomab estafenatox Oregovomab Pemtumomab^† Racotumomab Satumomab pendetide Solitomab Taplitumomab paptox Nofetumomab merpentan Pintumomab Tenatumomab Tositumomab
Chimeric	Amatuximab^§ Bavituximab^§ Brentuximab vedotin Carotuximab^† Cetuximab Derlotuximab biotin^§ Dinutuximab Ecromeximab^§ Ensituximab^§ Futuximab^§ Girentuximab^† Indatuximab ravtansine^§ Isatuximab Loncastuximab tesirine Margetuximab Mirvetuximab soravtansine Rituximab^# Siltuximab Ublituximab Zolbetuximab
Humanized	Abituzumab^§ Alemtuzumab Belantamab mafodotin Bevacizumab Bivatuzumab mertansine^§ Brontictuzumab^§ Cantuzumab mertansine^§ Cantuzumab ravtansine^§ Cirmtuzumab Citatuzumab bogatox^§ Clivatuzumab tetraxetan Cofetuzumab pelidotin Dacetuzumab^§ Demcizumab^§ Dalotuzumab^§ Denintuzumab mafodotin^§ Elotuzumab Emactuzumab Emibetuzumab^§ Enoblituzumab^§ Epcoritamab Etaracizumab^§ Farletuzumab^§ Ficlatuzumab^§ Flotetuzumab^§ Gemtuzumab ozogamicin Glofitamab Imgatuzumab^§ Inotuzumab ozogamicin Labetuzumab^§ Lifastuzumab vedotin^§ Lintuzumab^§ Lorvotuzumab mertansine^§ Lumretuzumab^§ Matuzumab^§ Milatuzumab^§ Naxitamab Nimotuzumab^† Obinutuzumab Ocaratuzumab^§ Otlertuzumab^§ Onartuzumab^§ Oportuzumab monatox^† Parsatuzumab^§ Pertuzumab Pinatuzumab vedotin^§ Polatuzumab vedotin Rosmantuzumab Rovalpituzumab tesirine^† Sacituzumab govitecan Sibrotuzumab^§ Simtuzumab^§ Sofituzumab vedotin^§ Tacatuzumab tetraxetan^§ Tigatuzumab^§ Trastuzumab^# (+deruxtecan / +emtansine) Tucotuzumab celmoleukin^§ Vandortuzumab vedotin^§ Vanucizumab^§ Veltuzumab^§ Vorsetuzumab mafodotin^§
Rat/mouse hybrid	Catumaxomab Ertumaxomab^§
Chimeric + humanized	Depatuxizumab mafodotin^† Duvortuxizumab Ontuxizumab^§