Tisotumab vedotin

Tisotumab vedotin  is an antibody-drug conjugate (ADC) targeted to tissue factor (TF), a protein involved in tumor signaling and angiogenesis.1 It is composed of Genmab's human monoclonal antibody (mAb) that binds to TF and Seattle Genetics' ADC technology that utilizes a cleavable linker and the cytotoxic drug 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

The presences of 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 Genmab has entered a collaboration for tisotumab vedotin with Seattle Genetics. Tisotumab vedotin is in clinical development to treat cervical cancer and other 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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Cervical cancer originates in the cells lining the cervix, which connects the uterus to the birth canal. About 13,240 women were estimated to be diagnosed with cervical cancer in the U.S. in 2018, with an estimated 4,170 deaths.1 Globally, it was estimated that 570,000 people would be diagnosed and 311,000 would die from the disease in 2018, the vast majority of these patients being in the developing world.2 Routine medical examinations and the human papillomavirus (HPV) vaccine have had a positive impact on the incidence of cervical cancer in the developed world. Despite these advances, women are still diagnosed with cervical cancer, which can have a devastating impact, particularly in the recurrent or metastatic setting. Standard therapies for previously treated recurrent/metastatic cervical cancer generally result in response rates of less than 15 percent and a median overall survival of 6 to 8 months.3-10

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 design11

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.  

References

1  National Cancer Institute SEER. “Cancer Stat Facts: Cervical Cancer.” Available at https://seer.cancer.gov/statfacts/html/cervix.html. Accessed December 2018
2  Globocan 2018. World Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed December 2018
3 Miller et al., Gynecol Oncol 2008; 110:65
4 Bookman et al., Gynecol Oncol 2000; 77:446
5 Garcia et al.,Am J Clin Oncol 2007; 30:428
6 Muggia et al., J Clin Oncol 2009; 27:1069
7 Monk et al., J Clin Oncol 2009; 27:1069
8 Santin et al., Genecol Oncol 2011; 122:495
9 Schellens, J Clin Oncol 35, 2017 (suppl; abstr 5514)
10 Hollebecque et al., J Clin Oncol 35, 2017 (suppl; abstr 6025)
11 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.

 

Ovarian cancer is a type of solid tumor where malignant cells are found either inside or near the ovaries. For women between the ages of 35 to 74, ovarian cancer is the fifth leading cause of cancer related death.1 In 2018 it was estimated that there were over 24,000 new cases of ovarian cancer and 14,000 deaths due to the disease in the U.S.2  When diagnosed and treated early, the five-year survival rate is over 90%. However, as ovarian cancer does not have any specific symptoms and there are currently no early detection tests, only about 20% of cases are found in the early stages of the disease.1

1
National Ovarian Cancer Coalition, “What is Ovarian Cancer,” http://ovarian.org/about-ovarian-cancer/what-is-ovarian-cancer accessed March 2019 
2Globocan 2018. United States of America Fact Sheet,https://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdfaccessed March 2019