Evolving Therapy in Cervical Cancer: Tisotumab Vedotin’s Mechanism of Action

Transcript:

Rebecca Arend, MD, MPH: My name is Rebecca Arend. I’m a gynecologic oncologist at the University of Alabama at Birmingham, and I’m going to talk about some of the exciting data that came out of ESMO [European Society for Medical Oncology Congress], specifically with the drug tisotumab vedotin. First, I want to talk about how metastatic cervical cancer has been managed following progression on chemotherapy. Historically we haven’t had a lot of options. The most exciting data before this were from GOG-0240, which was published in 2014 when we started adding bevacizumab to a platinum doublet. That’s improved survival by only 3.7 months, and the overall response rate was 48% vs 36%. That’s important to have this as a historical perspective.

I briefly want to describe tisotumab vedotin, or TV. Specifically, I want to explain the mechanism of action and the rationale for its use in cervical cancer. TV [tisotumab vedotin] is a tissue factor–directed antibody. It’s an antibody-drug conjugate that has a payload of a microtubule disrupting agent, or MMAE, and that agent acts like a taxane. TV [tisotumab vedotin] is a monoclonal antibody, and it’s conjugated to MMAE and covalently linked. When the TV [tisotumab vedotin] binds to the TF [tissue factor], MMAE is released via a proteasome cleavage linker. This leads to cell death by disrupting cell division. In addition to direct antitumor action, it also has immunomodulatory effects, which leads to an activation of an adaptive immune response. Therefore, TV [tisotumab vedotin] has multiple antitumor effects: bystander killing, antibody-dependent cellular phagocytosis, antibody-dependent cellular cytotoxicity, and immunologic cell death. Tissue factor in healthy cells is used to initiate a coagulation cascade after a vascular injury. In cancer, it’s co-opted by these tumor cells to promote tumor growth, angiogenesis, and metathesis. This is an especially attractive agent for cervical cancer given the high level of expression of tissue factor on cervical cancer cells.

Transcript edited for clarity.