Overview
Tisotumab vedotin is a tissue factor-directed antibody-drug conjugate (ADC) comprised of an anti-tissue factor (TF) human IgG1-kappa antibody conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent, via a protease-cleavable valine-citrulline linker. Each monoclonal antibody molecule carries an average of four MMAE molecules. Tisotumab vedotin is the first TF-directed ADC that works by binding to TFs expressed on solid tumours. TF is a primary initiator of the extrinsic blood coagulation cascade and plays a key role in tumor-associated angiogenesis, progression, and metastasis for tumor survival. TF is a novel target for cancers, as it is often overexpressed on solid tumours, including cervical cancer, and it is associated with poor clinical outcomes. Tisotumab vedotin targets TF-expressing cells to deliver MMAE to induce direct cytotoxicity and bystander killing of neighboring cells. On September 20, 2021, the FDA granted accelerated approval to tisotumab vedotin-tftv for the treatment of recurrent or metastatic cervical cancer in adults in whom the disease progressed during or after chemotherapy. This is the first and only approved antibody-drug conjugate for this therapeutic indication. The approval was based on tumour response and the durability of the response as demonstrated in InnovaTV 204 (NCT03438396): in this trial, the objective response rate was 24% and the median response duration was 8.3 months. Tisotumab vedotin-tftv is marketed under the trade name Tivdak as an intravenous injection. Tisotumab vedotin is currently under investigation as a treatment for other solid tumors, including ovarian, lung, colorectal, pancreatic, and head and neck cancers. It is also being investigated for the combination use with other chemotherapeutic agents for recurrent or metastatic cervical cancer.
Background
Tisotumab vedotin is a tissue factor-directed antibody-drug conjugate (ADC) comprised of an anti-tissue factor (TF) human IgG1-kappa antibody conjugated to monomethyl auristatin E (MMAE), a microtubule-disrupting agent, via a protease-cleavable valine-citrulline linker. Each monoclonal antibody molecule carries an average of four MMAE molecules. Tisotumab vedotin is the first TF-directed ADC that works by binding to TFs expressed on solid tumours. TF is a primary initiator of the extrinsic blood coagulation cascade and plays a key role in tumor-associated angiogenesis, progression, and metastasis for tumor survival. TF is a novel target for cancers, as it is often overexpressed on solid tumours, including cervical cancer, and it is associated with poor clinical outcomes. Tisotumab vedotin targets TF-expressing cells to deliver MMAE to induce direct cytotoxicity and bystander killing of neighboring cells. On September 20, 2021, the FDA granted accelerated approval to tisotumab vedotin-tftv for the treatment of recurrent or metastatic cervical cancer in adults in whom the disease progressed during or after chemotherapy. This is the first and only approved antibody-drug conjugate for this therapeutic indication. The approval was based on tumour response and the durability of the response as demonstrated in InnovaTV 204 (NCT03438396): in this trial, the objective response rate was 24% and the median response duration was 8.3 months. Tisotumab vedotin-tftv is marketed under the trade name Tivdak as an intravenous injection. Tisotumab vedotin is currently under investigation as a treatment for other solid tumors, including ovarian, lung, colorectal, pancreatic, and head and neck cancers. It is also being investigated for the combination use with other chemotherapeutic agents for recurrent or metastatic cervical cancer.
Indication
Tisotumab vedotin is indicated for the treatment of adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.
Associated Conditions
- Metastatic Cervical Cancer
- Recurrent Cervical Cancer
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/05/01 | Phase 4 | Recruiting | |||
2024/06/14 | Phase 3 | Recruiting | |||
2023/05/19 | Phase 1 | Completed | |||
2021/01/06 | Phase 3 | Active, not recruiting | |||
2019/04/12 | Phase 1 | Completed | |||
2018/12/24 | Phase 1 | Active, not recruiting | |||
2018/09/04 | Phase 2 | Completed | |||
2018/04/02 | Phase 2 | Active, not recruiting | |||
2018/02/19 | Phase 2 | Completed | |||
2017/08/10 | Phase 2 | Completed |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Seagen Inc. | 51144-003 | INTRAVENOUS | 40 mg in 4 mL | 1/31/2022 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 3/28/2025 | ||
Authorised | 3/28/2025 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||