Tisotumab vedotin

Summary

Tisotumab vedotin (Tivdak) is an FDA-approved ADC targeting tissue factor, indicated for adults with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy. It combines targeted delivery of MMAE to TF-expressing tumor cells with immune effector functions.

Mechanism of Action

Tisotumab vedotin is an antibody-drug conjugate consisting of a human monoclonal antibody targeting tissue factor (TF/CD142) conjugated via a protease-cleavable linker to monomethyl auristatin E (MMAE), a microtubule-disrupting agent. Upon binding to TF on tumor cell surfaces, the conjugate is internalized, MMAE is released intracellularly, disrupting microtubule polymerization and inducing apoptosis. Additional mechanisms include antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Routes of Administration

Goals & Uses

• Treatment of endometrial cancerOncologyModerate
• Treatment of bladder/urothelial cancerOncologyLow
• Treatment of head and neck squamous cell carcinomaOncologyLow
• Treatment of recurrent or metastatic cervical cancerOncologyHigh

Contraindications

• Hypersensitivity to tisotumab vedotin or excipientsAllergy/immunologicHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Severe ocular surface diseaseOphthalmologicHigh

Adverse Effects

• Peripheral neuropathyNeurologicalCommon
• AlopeciaDermatologicCommonHair loss
• Nausea and fatigueGastrointestinal/constitutionalCommon
• Ocular toxicity (conjunctivitis, keratitis, dry eye, corneal ulceration)OphthalmologicCommon
• Infusion-related reactionsHypersensitivityUncommon
• Hemorrhage / bleeding eventsHematologic/vascularCommon

Drug Interactions

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine)Moderate
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole)Moderate
• Anticoagulants / antiplatelet agentsModerate

Population Constraints

• Pregnant or lactating individualsReproductiveAbsolute
• Pediatric patientsAgeRelative
• Patients with active or severe ocular diseaseOphthalmologicRelative
• Patients with severe hepatic impairmentHepaticRelative

Regulatory Status

• European UnionApprovedApproved: Recurrent or metastatic cervical cancer in adults who have received prior platinum-based chemotherapyEuropean Commission granted conditional marketing authorization in 2022; subsequently converted to full approval.
• United StatesApprovedApproved: Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (adults)Initially granted accelerated approval September 2021; converted to regular approval November 2023 based on innovaTV 301 overall survival data.
• United KingdomApprovedApproved: Recurrent or metastatic cervical cancer with disease progression on or after prior chemotherapyApproved by MHRA; NICE technology appraisal conducted for NHS reimbursement consideration.

FDA accelerated approval granted September 2021 for recurrent or metastatic cervical cancer; regular approval granted November 2023 based on confirmatory trial (innovaTV 301). Carries a Boxed Warning for ocular toxicity (conjunctival and corneal adverse reactions). Risk Evaluation and Mitigation Strategy (REMS) program not required but ophthalmologic monitoring mandated.

Evidence & Sources

No sources recorded yet.