Tisotumab Vedotin Combinations for Cervical Cancer

Not currently recruiting at 79 trial locations

Overseen By Genmab A/S Trial Information

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: Anticoagulants

Disqualifiers: Bilateral hydronephrosis, Gastrointestinal obstruction, Bleeding issues, Ocular disease, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called tisotumab vedotin, alone or combined with other drugs, for recurrent or advanced cervical cancer. Researchers are testing different combinations, such as with bevacizumab (Avastin), pembrolizumab (KEYTRUDA), or carboplatin, to find the most effective dose. Individuals with cervical cancer who have tried other treatments or have not yet received systemic therapy might be suitable candidates. The trial aims to evaluate the effectiveness of these combinations and determine the best dose for future studies. As a Phase 1 and Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you require anti-coagulation therapy, you may not be eligible for certain parts of the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tisotumab vedotin, whether used alone or with other drugs, is generally well-tolerated by people with cervical cancer. When used by itself, 13% of patients experienced serious side effects. The most common issues included eye problems, such as conjunctivitis, affecting 55% of patients, and 2% experienced nerve issues or fever.

When combined with other drugs like bevacizumab, pembrolizumab, or carboplatin, studies have found the treatment to be safe and manageable. Researchers are carefully studying these combinations to ensure they are safe and effective against cancer. Some of these combinations remain in early trial phases, so they are closely monitored for safety before wider use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Tisotumab Vedotin for cervical cancer because it works differently from many existing treatments. While traditional therapies often involve chemotherapy or radiation, Tisotumab Vedotin is an antibody-drug conjugate that specifically targets tissue factor, a protein commonly found on the surface of cervical cancer cells. This targeted approach allows the drug to deliver a potent cell-killing agent directly to the cancer cells, potentially increasing effectiveness and minimizing damage to healthy cells. Furthermore, when combined with drugs like bevacizumab, pembrolizumab, or carboplatin, it may enhance the overall treatment response, offering new hope for patients who have previously been treated.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

Research has shown that Tisotumab Vedotin, a type of targeted cancer treatment, can effectively treat cervical cancer. In earlier studies, 17.8% of patients responded positively to Tisotumab Vedotin, compared to only 5.2% with standard chemotherapy. This trial will administer Tisotumab Vedotin alongside other drugs like bevacizumab, pembrolizumab, or carboplatin, which have shown promising results for advanced cervical cancer. Tisotumab Vedotin delivers chemotherapy directly to cancer cells, helping to shrink tumors. Early evidence suggests that combining it with other medications might enhance its effectiveness. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for individuals with recurrent or stage IVB cervical cancer who haven't had systemic therapy (for certain arms) or have tried at most two therapies. Participants must not be pregnant, agree to contraception, and understand the trial's procedures. They should have a performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

Participants of childbearing potential must agree to use adequate contraception during and for 6 months after the last dose of trial treatment administration

Must sign an informed consent form (ICF) indicating the trial subject understands the purpose of and procedures required for the trial and are willing to participate in the trial

My cervical cancer has worsened after 1-2 treatments.

Exclusion Criteria

I've had recent wound healing issues that needed medical help.

I do not have any current eye surface diseases or a history of severe eye inflammation.

I have had serious bleeding that needed a blood transfusion in the last 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of tisotumab vedotin in combination with other agents to determine the Recommended Phase 2 Dose (RP2D)

21-day cycles

Visits every 3 weeks

Dose Expansion

Participants receive the RP2D of tisotumab vedotin in combination with other agents or as monotherapy

28-day cycles

Visits every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Carboplatin
• Pembrolizumab
• Tisotumab Vedotin

Trial Overview

The study tests Tisotumab Vedotin alone and combined with Bevacizumab, Pembrolizumab, or Carboplatin in patients with advanced cervical cancer. It includes dose escalation to find safe levels followed by an expansion phase to further assess effectiveness at these doses.

How Is the Trial Designed?

Group I: H: Tisotumab vedotin + pembrolizumab + carboplatin +/- bevacizumab Experimental Treatment 4 Interventions

Dose expansion: Tisotumab vedotin in combination with pembrolizumab and carboplatin with or without bevacizumab once every three weeks in previously untreated patients

Group II: G: Tisotumab vedotin monotherapy Experimental Treatment 1 Intervention

Dose expansion: Tisotumab vedotin monotherapy weekly for three weeks and 1 week off (28 day treatment cycle) in previously treated patients.

Group III: F: Tisotumab vedotin + pembrolizumab Experimental Treatment 2 Interventions

Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients

Group IV: E: Tisotumab vedotin + pembrolizumab Experimental Treatment 2 Interventions

Dose expansion: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously untreated patients

Group V: D: Tisotumab vedotin + carboplatin Experimental Treatment 2 Interventions

Dose expansion:Tisotumab vedotin in combination with carboplatin once every three weeks in previously untreated patients

Group VI: C: Tisotumab vedotin + carboplatin Experimental Treatment 2 Interventions

Dose escalation: Tisotumab vedotin in combination with carboplatin once every three weeks in previously treated patients

Group VII: B: Tisotumab vedotin + pembrolizumab Experimental Treatment 2 Interventions

Dose escalation: Tisotumab vedotin in combination with pembrolizumab once every three weeks in previously treated patients

Group VIII: A: Tisotumab Vedotin + bevacizumab Experimental Treatment 2 Interventions

Dose escalation: Tisotumab vedotin in combination with bevacizumab once every three weeks in previously treated patients

Tisotumab Vedotin is already approved in United States for the following indications:

Approved in United States as Tivdak for:

• Recurrent or metastatic cervical cancer with disease progression on or after chemotherapy

Who Is Running the Clinical Trial?

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

Seagen Inc.

Lead Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Belgian Gynaecological Oncology Group

Collaborator

Trials

15

Recruited

4,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Gynecologic Oncology Group

Collaborator

Trials

251

Recruited

65,400+

Genmab

Industry Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Published Research Related to This Trial

Tisotumab vedotin-tftv (Tivdak) is an accelerated-approved treatment for adults with recurrent or metastatic cervical cancer who have experienced disease progression after chemotherapy.

In clinical trials, 60% of patients experienced ocular adverse effects, highlighting the importance of following premedication and eye care guidelines to minimize these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug Treats Cervical Cancer. Aschenbrenner, DS.[2023]

Tisotumab vedotin (Tivdak™) is an antibody-drug conjugate specifically designed to target tissue factor in tumors, combining a monoclonal antibody with a potent drug, monomethyl auristatin E (MMAE).

It received accelerated approval in the USA for treating recurrent or metastatic cervical cancer in adults who have experienced disease progression after chemotherapy, based on promising results from a phase II trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisotumab Vedotin: First Approval. Markham, A.[2022]

Tisotumab vedotin is an FDA-approved antibody-drug conjugate that targets tissue factor on cervical cancer cells, delivering a cytotoxic agent directly to the tumor, making it a promising treatment for recurrent or metastatic cervical cancer.

Clinical trials indicate that tisotumab vedotin can lead to significant and long-lasting remission in patients, with manageable safety profiles, providing a new option for those who have not responded to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin for the treatment of cervical carcinoma. Song, X., Li, R., Wang, H., et al.[2022]

The antibody-drug conjugate tisotumab vedotin (TV) has been shown to significantly increase the probability of objective response in patients with recurrent or metastatic cervical cancer as the maximum serum concentration (Cmax) increases, indicating its efficacy in treatment.

However, higher exposure levels of TV are also associated with an increased risk of treatment-related adverse events, particularly ocular side effects, suggesting a need for careful monitoring of dosage to balance efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. Passey, C., Voellinger, J., Gibiansky, L., et al.[2023]

Tisotumab vedotin (TV) is the first antibody-drug conjugate targeting tissue factor in cervical cancer, showing promising results in treating recurrent or metastatic cases with a favorable safety profile and limited severe side effects.

The FDA granted expedited approval for TV based on positive preliminary data, and ongoing trials are expected to further establish its efficacy and potentially set it as a new standard of care for advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data. Agostinelli, V., Musacchio, L., Camarda, F., et al.[2023]

Citations

1.

tivdakhcp.com

tivdakhcp.com/efficacy/

Efficacy | Tivdak® (tisotumab vedotin-tftv) HCP Site

TIVDAK (tisotumab vedotin-tftv) treated patients had a 17.8% overall response rate compared to a 5.2% overall response rate with IC chemotherapy.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12127362/

a systematic review and meta-analysis of single-arm studies

This study was conducted to evaluate the efficacy and safety of Tisotumab Vedotin (TV) in the treatment of recurrent/metastatic cervical cancer ...

3.

fda.gov

fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisotumab-vedotin-tftv-recurrent-or-metastatic-cervical-cancer

FDA approves tisotumab vedotin-tftv for recurrent or ...

FDA approves tisotumab vedotin-tftv for recurrent or metastatic cervical cancer ... Additional efficacy outcome measures were progression ...

4.

nature.com

nature.com/articles/s41598-025-14710-9

Signal mining and risk analysis of tisotumab vedotin ...

Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer ... Bevacizumab for advanced cervical ...

5.

ons.org

ons.org/publications-research/voice/news-views/04-2024/fda-approves-tisotumab-vedotin-tftv-recurrent-or

FDA Approves Tisotumab Vedotin-Tftv for Recurrent or ...

The US Food and Drug Administration (FDA) granted traditional approval to tisotumab vedotin-tftv (Tivdak ® ) for recurrent or metastatic cervical cancer.

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2024/761208s007lbl.pdf

Tivdak - accessdata.fda.gov

The data in the WARNINGS AND PRECAUTIONS section reflect exposure to TIVDAK in 425 patients with recurrent or metastatic cervical cancer who received at least ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10062530/

Tisotumab Vedotin Safety and Tolerability in Clinical Practice

Tisotumab vedotin-tftv, an antibody-drug conjugate indicated for the treatment of adult patients with recurrent or metastatic cervical cancer ...

8.

aetna.com

aetna.com/cpb/medical/data/900_999/0998.html

Tisotumab Vedotin-tftv (Tivdak) - Medical Clinical Policy ...

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