General Information

Tivdak (tisotumab vedotin-tftv) is a tissue factor-directed antibody and microtubule inhibitor conjugate.

Tivdak is specifically indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

Tivdak is supplied as an injection for intravenous administration. The recommended dose is 2 mg/kg (up to a maximum of 200 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

Mechanism of Action

Tivdak (tisotumab vedotin-tftv) is a tissue factor (TF)-directed antibody drug conjugate (ADC). The antibody is a human IgG1 directed against cell surface TF. TF is the primary initiator of the extrinsic blood coagulation cascade. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggests that the anticancer activity of tisotumab vedotin-tftv is due to the binding of the ADC to TF expressing cancer cells, followed by internalization of the ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and apoptotic cell death. In vitro, tisotumab vedotin-tftv also mediates antibody-dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.

Side Effects

Adverse effects associated with the use of Tivdak may include, but are not limited to, the following:

• hemoglobin decreased
• fatigue
• lymphocytes decreased
• nausea
• peripheral neuropathy
• alopecia
• epistaxis
• conjunctival adverse reactions
• hemorrhage
• leukocytes decreased
• creatinine increased
• dry eye
• prothrombin international normalized ratio increased
• activated partial thromboplastin time prolonged
• diarrhea
• rash

The Tivdak drug label comes with the following Black Box Warning: Tivdak caused changes in the corneal epithelium and conjunctiva resulting in changes in vision, including severe vision loss, and corneal ulceration. Conduct an ophthalmic exam at baseline, prior to each dose, and as clinically indicated. Adhere to premedication and required eye care before, during, and after infusion. Withhold Tivdak until improvement and resume, reduce the dose, or permanently discontinue, based on severity.

Clinical Trial Results

Tivdak was approved under the FDA’s Accelerated Approval Program based on tumor response and the durability of the response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

FDA approval was based on the innovaTV 204 trial, an open-label, multicenter, single-arm phase 2 trial that evaluated tisotumab vedotin in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. In the innovaTV 204 clinical trial, Tivdak was evaluated in 101 patients with recurrent or metastatic cervical cancer who had received no more than two prior systemic regimens in the recurrent or metastatic setting, including at least one prior platinum-based chemotherapy regimen. Results from the trial showed a 24 percent confirmed objective response rate (ORR), as assessed by an independent review committee (IRC) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The median duration of response (DOR) was 8.3 months.