Tisotumab Vedotin vs Chemotherapy for Cervical Cancer

(innovaTV 301 Trial)

Not currently recruiting at 446 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Seagen, a wholly owned subsidiary of Pfizer

Must not be taking: MMAE-containing drugs

Disqualifiers: Neuroendocrine, Bleeding issues, Ocular disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 25 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a new drug, tisotumab vedotin, works better than chemotherapy for treating cervical cancer that has spread or returned after previous treatments. Participants will be divided into two groups: one will receive tisotumab vedotin, and the other will receive one of five different chemotherapy drugs. The trial seeks individuals with cervical cancer that has returned or spread after standard chemotherapy and who have noticeable symptoms. Participants and their doctors will know which treatment they receive. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study doctor to understand how your current treatments might interact with the trial requirements.

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

Research has shown that tisotumab vedotin is generally safe for treating cervical cancer. Various studies reported eye-related side effects in 55% of patients. However, the FDA has approved this treatment for patients whose cervical cancer has returned or spread after chemotherapy, indicating it is usually well-tolerated.

Chemotherapy drugs like topotecan, vinorelbine, gemcitabine, pemetrexed, and irinotecan have been used in cancer treatment for many years. Each drug has its own side effects, but doctors are familiar with them and monitor them closely. Participants will discuss with their doctors which chemotherapy option is best, considering the possible side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cervical cancer?

Unlike the standard chemotherapy options for cervical cancer, which typically include drugs like gemcitabine, irinotecan, and topotecan, Tisotumab Vedotin offers a unique approach by targeting tissue factor, a protein commonly found on the surface of cancer cells. This targeted mechanism allows Tisotumab Vedotin to deliver a cytotoxic agent directly to the cancer cells, potentially sparing healthy cells and reducing side effects. Researchers are excited about this treatment because it combines the precision of targeted therapy with the potency of chemotherapy, possibly improving outcomes for patients who have limited options.

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

This trial will compare Tisotumab Vedotin with chemotherapy for treating cervical cancer. Studies have shown that Tisotumab Vedotin outperforms chemotherapy, with 17.8% of patients responding to Tisotumab Vedotin compared to only 5.2% for chemotherapy. Thus, more patients benefited from Tisotumab Vedotin. The FDA has approved Tisotumab Vedotin for cases where cervical cancer has recurred or spread, demonstrating its effectiveness for this condition. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

This trial is for individuals with cervical cancer that has returned or spread, who have already tried certain standard treatments without success. They should have had one or two previous treatments for their condition and must be in a relatively good physical state (able to perform daily activities without significant limitations). People with serious eye conditions, bleeding risks, recent major surgery, severe nerve damage, or those who've taken drugs containing MMAE are not eligible.

Inclusion Criteria

Has life expectancy of at least 3 months.

Measurable disease according to RECIST v1.1 as assessed by the investigator.

My cancer progressed after receiving standard chemotherapy or treatments.

Exclusion Criteria

My cancer is not neuroendocrine, lymphoid, sarcomatoid, or any other type not listed in the criteria.

I have never been treated with drugs containing MMAE.

I have not had major surgery in the last 4 weeks or minor surgery in the last 7 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either tisotumab vedotin or one of five chemotherapy drugs as per random assignment

Up to 25 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 25 months

What Are the Treatments Tested in This Trial?

Interventions

• Gemcitabine
• Irinotecan
• Pemetrexed
• Tisotumab Vedotin
• Topotecan
• Vinorelbine

Trial Overview The study compares the effectiveness of tisotumab vedotin against traditional chemotherapy drugs (topotecan, vinorelbine, gemcitabine, irinotecan, pemetrexed) in treating recurrent or metastatic cervical cancer. Participants will be randomly assigned to receive either tisotumab vedotin or their choice of one of the chemotherapy drugs.

How Is the Trial Designed?

Group I: Tisotumab vedotin Experimental Treatment 1 Intervention

Tisotumab vedotin monotherapy

Group II: Chemotherapy Active Control 5 Interventions

Investigator's choice of one chemotherapy treatment (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed)

Gemcitabine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Breast cancer
• Ovarian cancer
• Non-small cell lung cancer

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

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 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]

In a study involving 9 patients with cervical cancer, combination therapy using irinotecan and nedaplatin showed a 40% response rate in patients receiving treatment before surgery and a 75% response rate in those with recurrent disease.

While the treatment was effective, it also led to significant side effects, including grade 3 or 4 adverse events such as leukopenia in 4 patients, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. Hiruma, R., Kamide, T., Anzai, N., et al.[2018]

Irinotecan (CPT-11) has shown response rates of 13% to 20% in treating refractory or recurrent cervical cancer, indicating some level of efficacy in this challenging condition.

The combination of irinotecan with cisplatin has been studied, but the treatment is associated with significant hematologic and gastrointestinal toxicities, highlighting the need for further research to optimize safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Irinotecan in cervical cancer. Kavanagh, JJ., Verschraegen, CF., Kudelka, AP.[2018]

Irinotecan (CPT-11) demonstrated a 21% overall response rate in 42 patients with refractory squamous cell cancer of the cervix, with a median survival of 6.4 months, and a significant survival advantage for those who responded to treatment (12.6 months vs. 5.1 months).

The treatment was associated with notable toxicities, including severe nausea and vomiting (45%), diarrhea (24%), and anemia (62%), indicating the need for careful monitoring of gastrointestinal and hematologic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. Verschraegen, CF., Levy, T., Kudelka, AP., et al.[2018]

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. tivdak.com tivdak.com/study-results/

Study Results for Tivdak® (tisotumab vedotin-tftv) Tivdak was studied in a clinical trial of 502 people with cervical cancer that has returned or has spread, and who have received chemotherapy that did not work ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10543937/

Therapeutic Potential of Tisotumab Vedotin in the Treatment of ... Therapeutic Potential of Tisotumab Vedotin in the Treatment of Recurrent or Metastatic Cervical Cancer: A Short Report on the Emerging Data.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04697628?term=AREA%5BBasicSearch%5D(tisotumab%20vedotin%20OR%20HuMax-TF-ADC%20OR%20TF-011-MMAE)&rank=10&tab=results

Study Results | Tisotumab Vedotin vs Chemotherapy in ... The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

5. 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 ...

6. tivdakhcp.com tivdakhcp.com/additional-data/

Additional data from innovaTV 301 Learn about Tivdak's safety profile ... Ocular adverse reactions occurred in 55% of patients with cervical cancer treated with TIVDAK across clinical trials.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35962528/

A Review of Tisotumab Vedotin-tftv in Recurrent or ... With a manageable safety profile and promising anticancer activity, TV warrants consideration as a novel targeted agent for the treatment of ...

8. ir.genmab.com ir.genmab.com/news-releases/news-release-details/tivdakr-tisotumab-vedotin-tftv-receives-us-fda-approval-treat

TIVDAK® (tisotumab vedotin-tftv) Receives U.S. FDA ... TIVDAK is the first antibody-drug conjugate (ADC) with demonstrated overall survival data to be granted full FDA approval in this patient population.

9. ascopost.com ascopost.com/issues/september-25-2024/tisotumab-vedotin-tftv-for-recurrent-or-metastatic-cervical-cancer/

Tisotumab Vedotin-tftv for Recurrent or Metastatic Cervical ... Tisotumab vedotin-tftv (Tivdak) was granted regular approval for recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

10. clinicaltrials.gov clinicaltrials.gov/study/NCT03438396

NCT03438396 | A Trial of Tisotumab Vedotin in Cervical ... The purpose of the trial is to evaluate the efficacy and safety/tolerability of tisotumab vedotin in patients with previously treated, recurrent or ...