Tisotumab vedotin, known by its brand name Tivdak, is a targeted medication used in cancer treatment, designed to deliver potent chemotherapy directly to cancer cells. This medication is administered as an intravenous infusion. It aims to minimize damage to healthy cells that often occurs with traditional chemotherapy. Tisotumab vedotin was approved for medical use in the United States in September 2021, and in the European Union in March 2025.
Understanding Tisotumab Vedotin
Tisotumab vedotin is classified as an antibody-drug conjugate (ADC). An ADC combines the precision of an antibody with the cell-killing power of a chemotherapy drug. This design allows for a more targeted attack on cancer cells.
The antibody component of tisotumab vedotin is specifically engineered to recognize and attach to a protein called Tissue Factor (TF). Tissue Factor is often found in higher amounts on the surface of various cancer cells, including those in cervical cancer.
A special linker connects the antibody to a potent chemotherapy payload, which is monomethyl auristatin E (MMAE). This linker is designed to keep the chemotherapy inactive until the ADC reaches its target. The stability of this linker is important to prevent the premature release of the chemotherapy in the bloodstream, which helps reduce systemic toxicity.
How Tisotumab Vedotin Targets Cancer
The mechanism of action for tisotumab vedotin begins with its antibody portion binding to Tissue Factor (TF) proteins present on the surface of cancer cells. This binding is a highly specific interaction, ensuring the drug is delivered primarily to the cells that express this protein.
Once the tisotumab vedotin binds to the TF on the cancer cell surface, the entire antibody-drug conjugate is internalized. This process, known as receptor-mediated endocytosis, involves the cell taking the drug inside, encapsulating it within a cellular compartment.
Inside the cancer cell, the linker connecting the antibody and the chemotherapy payload is cleaved by enzymes within the cell’s lysosomes. This cleavage releases the active chemotherapy drug, monomethyl auristatin E (MMAE), directly into the cell’s cytoplasm. MMAE is a potent agent that disrupts microtubules, which are structures essential for cell division.
By interfering with microtubule formation, MMAE prevents the cancer cell from dividing and growing. This disruption leads to cell cycle arrest and ultimately triggers programmed cell death, known as apoptosis. This targeted delivery and intracellular release of the chemotherapy payload significantly reduce the damage to healthy cells compared to traditional chemotherapy, which often affects both cancerous and rapidly dividing healthy cells.
Cancers Treated by Tisotumab Vedotin
Tisotumab vedotin is approved for the treatment of adult patients with recurrent or metastatic cervical cancer. This specific indication applies to individuals whose disease has progressed after receiving prior chemotherapy treatments.
In clinical trials, tisotumab vedotin demonstrated improved outcomes compared to chemotherapy in patients with recurrent or metastatic cervical cancer. For instance, in one study, the median overall survival for patients treated with tisotumab vedotin was 11.5 months, compared to 9.5 months for those receiving chemotherapy.
The drug’s approval provides a new therapeutic avenue for patients who have limited options after their disease has progressed on or after initial chemotherapy. Tisotumab vedotin is the first antibody-drug conjugate to be approved for this specific patient population in cervical cancer.
Administering the Treatment and Managing Side Effects
Tisotumab vedotin is administered as an intravenous infusion, typically given over approximately 30 minutes. The treatment schedule generally involves receiving the infusion once every three weeks. Patients usually continue treatment until their disease progresses or they experience unacceptable side effects.
One notable side effect is ocular toxicity, which can affect the eyes in up to 60% of treated patients. Common eye problems reported include dry eye, conjunctivitis (inflammation of the eye lining), and corneal damage. To manage these effects, patients are typically prescribed three types of eye drops: steroid, vasoconstrictor, and lubricating eye drops, which are used before, during, and after each infusion.
Peripheral neuropathy, characterized by numbness or tingling in the hands or feet, is another common side effect, occurring in about 42% of patients. Bleeding is also frequently observed, with nosebleeds being the most common type, affecting approximately 60% of patients. More serious bleeding can occur, though it is less common.
Other common side effects include fatigue, nausea, hair loss, and changes in blood counts, such as decreased red blood cell counts. Patients may also experience muscle or joint pain, constipation, or diarrhea.