tisotumab vedotin-tftv — Drug Monograph

Tisotumab Vedotin (Tivdak) — Tissue Factor ADC for Cervical Cancer

Tisotumab vedotin (Tivdak) is a tissue factor (TF)-directed antibody-drug conjugate (ADC) for recurrent or metastatic cervical cancer. Tissue factor is overexpressed on cervical cancer cells; after binding and internalization, the cleavable linker releases the microtubule inhibitor MMAE, driving G2/M arrest and apoptosis. Its overall-survival benefit (innovaTV 301) converted the accelerated approval to full approval. Because ocular-surface toxicity is a signature adverse effect, tisotumab vedotin carries a mandatory eye-care prophylaxis regimen. This monograph covers tisotumab vedotin dosing (2 mg/kg IV every 3 weeks), tissue factor targeting, recurrent/metastatic cervical cancer indications, the eye-care prophylaxis checklist, and neuropathy monitoring.

Indications (FDA / NCCN)

• Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (innovaTV 301)
• Full approval based on an overall-survival benefit vs chemotherapy
• Tissue factor-directed ADC — no companion biomarker test required

Dosing

• Standard dose: 2 mg/kg (max 200 mg for ≥100 kg) IV over 30 min every 3 weeks
• Dose reductions: 1.3 mg/kg → 0.9 mg/kg; discontinue if not tolerated
• Continue until progression or unacceptable toxicity
• Do not treat patients unable to comply with ocular prophylaxis

Monitoring

• Ophthalmic exam before starting, before each cycle for the first 9 cycles, then as indicated
• Mandatory eye care: topical steroid drops before + 72 h after each infusion; cooling eye pads during infusion; preservative-free lubricants
• No contact lenses during treatment unless advised
• Peripheral neuropathy assessment

Brand names: Tivdak

Drug class: Antibody-Drug Conjugate

Mechanism of Action

Anti-tissue factor (TF) monoclonal antibody conjugated to the microtubule-disrupting agent MMAE (monomethyl auristatin E) via a protease-cleavable valine-citrulline linker. TF is overexpressed on cervical cancer cells. After internalization, MMAE is cleaved, binds tubulin, and induces G2/M arrest and apoptosis. Anti-tumor immune effects (ADCC) may also contribute.

FDA Indications

• Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (accelerated approval September 2021, innovaTV 204; converted to regular approval 2023 based on innovaTV 301 demonstrating PFS benefit: HR 0.67)

Common Side Effects

• Conjunctival adverse reactions (conjunctivitis, conjunctival hyperemia)
• Corneal adverse reactions (keratitis)
• Peripheral neuropathy
• Alopecia
• Epistaxis
• Nausea
• Fatigue
• Hemorrhage
• Diarrhea

Clinical Pearl

The mandatory eye-care regimen (topical corticosteroid drops before and for 72 hours after each infusion, cooling eye pads during the infusion, preservative-free lubricants, and no contact lenses) is uniquely associated with tisotumab vedotin and is intended to reduce ocular-surface exposure and inflammation. This prophylaxis is more elaborate than for other ocular-toxic ADCs and must be rigorously followed to prevent severe, vision-threatening keratitis. innovaTV 301 converted the accelerated…

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