Tisotumab vedotin
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | DRUG-TISOTUMAB-VEDOTIN |
|---|---|
| Type | Drug |
| Aliases | Tisotumab vedotin-tftvTivdakТисотумаб ведотин |
| Status | reviewed 2026-04-29 | pending_clinical_signoff |
| Diseases | DIS-CERVICAL |
| Sources | SRC-CIVIC SRC-ESMO-CERVICAL-2024 SRC-NCCN-CERVICAL-2025 |
Drug Facts
| Class | Anti-tissue-factor (TF / CD142) antibody-drug conjugate (ADC) with MMAE payload |
|---|---|
| Mechanism | Antibody-drug conjugate composed of a fully human IgG1 anti-tissue- factor (TF / CD142 / Factor III / coagulation factor III) monoclonal antibody (tisotumab) covalently linked via a cleavable protease-sensitive valine-citrulline linker to monomethyl auristatin E (MMAE), a tubulin-polymerization inhibitor. TF is broadly overexpressed on cervical carcinoma and other solid tumors, with limited / regulated expression on normal tissues. Tisotumab binds TF on tumor cells; the ADC is internalized; lysosomal protease cleavage releases MMAE intracellularly, disrupting tubulin and inducing apoptosis. Bystander effect on adjacent TF-low cells via released MMAE. Pivotal innovaTV 204 Phase II (Coleman Lancet Oncol 2021; n=101 pre-treated recurrent / metastatic cervical cancer post-platinum + post-bevacizumab where eligible) showed ORR 24%, mDOR 8.3 mo, mPFS 4.2 mo, mOS 12.1 mo → FDA accelerated appr... |
| Typical dosing | 2.0 mg/kg IV (max 200 mg) over 30 minutes once every 3 weeks, until disease progression or unacceptable toxicity. Premedicate prior to each infusion to mitigate ocular AEs: lubricating eye drops, vasoconstrictor ophthalmic drops, and topical ophthalmic corticosteroid + cooling eye-pads during infusion. Patients must use lubricating eye drops ≥6× daily throughout treatment. Mandatory ophthalmologic exam at baseline, prior to every cycle for first 9 cycles, and as clinically indicated. Dose reductions (1.5 → 1.2 → permanent discontinuation) for grade ≥2 ocular AEs, peripheral neuropathy, or hemorrhage. Hold for grade 3+ ocular AE until resolution to grade ≤1. |
| Ukraine registered | False |
| NSZU reimbursed | False |
| Ukraine last verified | 2026-04-29 |
Warnings
- Ocular toxicity (BOXED WARNING): conjunctivitis, dry eye, keratitis, corneal ulceration, vision loss — severe events including blindness reported. Mandatory baseline + per-cycle ophthalmologic exam; premedication regimen required; lubricating eye drops ≥6× daily. Hold for grade ≥2 ocular AE.
Notes
Tisotumab vedotin is the FIRST AND ONLY ADC approved for recurrent / metastatic cervical cancer 2L+ after platinum (with or without bevacizumab + pembrolizumab in 1L per CPS). It was the first oncology ADC targeting tissue factor (CD142). innovaTV 204 (Coleman Lancet Oncol 2021) — pivotal Phase II — n=101, post-platinum cervical cancer, ORR 24%, mDOR 8.3 mo, mPFS 4.2 mo, mOS 12.1 mo → FDA accelerated approval Sep 20, 2021. innovaTV 301 (Vergote NEJM 2024) — confirmatory Phase III — tisotumab vedotin vs IC chemo (topotecan, vinorelbine, gemcitabine, irinotecan, pemetrexed), n=502, mOS 11.5 vs 9.5 mo (HR 0.70, p=0.0038), mPFS 4.2 vs 2.9 mo (HR 0.67), ORR 17.8% vs 5.2% → FDA full approval Apr 29, 2024. NCCN-Cervical 2025 + ESMO-Cervical 2024 list tisotumab vedotin category 1 / preferred 2L+ recurrent/metastatic cervical cancer post-platinum (regardless of PD-L1 / pembrolizumab exposure in 1L). Class toxicity: ocular AEs are the dominant management challenge — mandatory ophtho monitoring + premedication + prophylactic eye drops protocol. Hemorrhage (TF target — vascular endothelium coagulation factor III) less prominent than feared pre-clinically, but anticoagulation interaction cauti...
Used By
Regimens
REG-TISOTUMAB-VEDOTIN-CERVICAL-2L- Tisotumab vedotin (recurrent/metastatic cervical cancer 2L+, innovaTV 204 / innovaTV 301)