Tisotumab Vedotin Combinations for Cervical Cancer

Recruiting at 70 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

214 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Tisotumab Vedotin for cervical cancer?

Tisotumab Vedotin has shown promising results in treating recurrent or metastatic cervical cancer, with clinical trials indicating significant and lasting tumor reduction in patients who have already undergone chemotherapy. The drug targets a protein on cancer cells, delivering a powerful agent directly to the tumor, and has been approved by the FDA for use in these cases. ^{1 2 3 4 5}

What safety information is available for Tisotumab Vedotin in treating cervical cancer?

Tisotumab Vedotin has been shown to be generally safe for humans, but it can cause some side effects like eye problems, nerve damage, and bleeding. These side effects are manageable with proper care, and the treatment has been approved for use in certain cervical cancer patients. ^{1 2 6 7 8}

What makes the drug Tisotumab Vedotin unique for treating cervical cancer?

Tisotumab Vedotin is unique because it is an antibody-drug conjugate that specifically targets tissue factor, a protein highly expressed on cervical cancer cells, delivering a powerful cancer-killing agent directly to the tumor. This targeted approach is different from traditional chemotherapy and has shown promising results in patients with recurrent or metastatic cervical cancer who have not responded to other treatments. ^{1 2 3 6 8}

What is the purpose of this trial?

This is an open label, multi-center trial of tisotumab vedotin monotherapy and in combination with bevacizumab, pembrolizumab, or carboplatin in subjects with recurrent or stage IVB cervical cancer. The trial consists of two-parts a dose escalation part and an expansion part. The expansion part of the trial will be initiated once the Recommended Phase 2 Dose (RP2D) of the combinations have been determined in the dose escalation part.

Eligibility Criteria

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

My cervical cancer has worsened after 1-2 treatments.

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

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

New Drug Treats Cervical Cancer. [2023]

2. Spain pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin for the treatment of cervical carcinoma. [2022]

3. New Zealand 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. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin in recurrent or metastatic cervical cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tisotumab vedotin in previously treated recurrent or metastatic cervical cancer (innovaTV 204/GOG-3023/ENGOT-cx6): a multicentre, open-label, single-arm, phase 2 study. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Tisotumab Vedotin: First Approval. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Tisotumab Vedotin Safety and Tolerability in Clinical Practice: Managing Adverse Events. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Exposure-safety and exposure-efficacy analyses for tisotumab vedotin for patients with locally advanced or metastatic solid tumors. [2023]