Tisotumab vedotin

Tisotumab vedotin (HuMax®-TF-ADC) is an antibody-drug conjugate (ADC) targeted to tissue factor (TF), a protein involved in tumor signaling and angiogenesis.1 It is composed of a human monoclonal antibody (mAb) specific for TF, a protease-cleavable linker, and the microtubule-disrupting agent monomethyl auristatin E (MMAE).1 TF is a transmembrane protein that is the main physiological initiator of coagulation and is involved in angiogenesis, cell adhesion, motility, and cell survival.2,3

TF is associated with poor prognosis.1 Based on its high expression in a broad range of solid tumors, and its rapid internalization, TF is a suitable target for an ADC approach.1,4,5 Tisotumab vedotin has shown strong ability to bind to TF and inhibit tumor growth in pre-clinical experiments.1 Genmab has entered a collaboration for tisotumab vedotin with Seattle Genetics. Tisotumab vedotin is in Phase I/II and II trials to treat multiple solid tumors.

References
1. Breij ECW, de Goeij BECG, Verploegen S, et al. An antibody-drug conjugate that targets tissue factor exhibits potent therapeutic activity against a broad range of solid tumors. Cancer Res. 2014;74(4):1214-1226.
2. Chu AJ. Tissue factor, blood coagulation, and beyond: an overview. Int J Inflam. 2011;2011:36784. doi:10.4061/2011/367284.
3. Ruf W. Tissue factor and cancer. Thromb Res. 2012;130:S84-S87.
4. Förster Y, Meye A, Albrecht S, Schwenzer B. Tissue factor and tumor: clinical and laboratory aspects. Clin Chim Acta. 2006;364(1-2):12-21.
5. Cocco E, Varughese J, Buza N, et al. Expression of tissue factor in adenocarcinoma and squamous cell carcinoma of the uterine cervix: implications for immunotherapy with hl-con1, a factor VII-IgGFc chimeric protein targeting tissue factor. BMC Cancer. 2011;11:263.

 

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Tisotumab vedotin is being tested in clinical studies in 8 solid tumors (ovary, cervix, endometrium, bladder, prostate, head and neck, esophagus, and lung).1 For more information on these studies, visit ClinicalTrials.gov.


Reference
1. US National Institutes of Health. Tisotumab vedotin continued treatment in patients with solid tumors.https://clinicaltrials.gov/ct2/show/NCT03245736?term=tisotumab+vedotin&rank=1. Updated August 10, 2017. Accessed March 14, 2018.

 

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Our Phase II clinical trial will enroll approximately 100 patients with recurrent or metastatic cancer of the cervix who have experienced disease progression on standard first-line therapy.

Trial design1

International-trial-of-TV_v3

ORR=overall response rate; RECIST=response evaluation criteria in solid tumors; IRC=independent review committee; DOR=duration of response; PFS=progression-free survival; QOL=quality of life.

Find out more.  

Reference
1. US National Institutes of Health. A trial of tisotumab vedotin in cervical cancer. 
https://clinicaltrials.gov/ct2/show/record/NCT03438396. Updated March 2, 2018. Accessed March 13, 2018.

 

 




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