Tisotumab Vedotin vs Chemotherapy for Cervical Cancer

(innovaTV 301 Trial)

Recruiting at 221 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

502 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is being done to find out whether tisotumab vedotin works better than chemotherapy to treat cervical cancer. People in this study have cervical cancer that has spread to other parts of the body (metastatic) or has come back after being treated (recurrent). Participants in this trial will be randomly assigned to one of two groups. One group will be treated with tisotumab vedotin. Participants in the other group will get one of five different chemotherapy drugs (topotecan, vinorelbine, gemcitabine, pemetrexed, or irinotecan). Participants and their doctors will know which group they are in. Participants in the chemotherapy group will decide with their study doctor which drug they will take.

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.

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

Research shows that topotecan, a component of the treatment, improves response rates and survival when combined with cisplatin for cervical cancer. Additionally, irinotecan has shown promising response rates in combination therapies for recurrent cervical cancer. ^{1 2 3 4 5}

Is Tisotumab Vedotin safe for humans?

Irinotecan, a drug sometimes used in cervical cancer treatment, has shown some side effects like low white blood cell counts (leukopenia), low platelet counts (thrombocytopenia), and vomiting. Gastrointestinal issues have been particularly problematic at high doses. ^{1 3 4 6 7}

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 on cervical cancer cells, delivering a potent cell division inhibitor directly to the tumor. This targeted approach allows for significant and lasting tumor reduction with a manageable safety profile, offering a novel option for patients with recurrent or metastatic cervical cancer who have progressed after chemotherapy. ^{3 8 9 10 11}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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) 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Update on the treatment of cervical and uterine carcinoma: focus on topotecan. [2019]

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

A feasibility study of topotecan with standard-dose cisplatin and concurrent primary radiation therapy in locally advanced cervical cancer. [2013]

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

Irinotecan in cervical cancer. [2018]

4. Japan pubmed.ncbi.nlm.nih.gov

[Combined irinotecan (CPT-11) and nedaplatin (254-S) therapy for advanced and/or recurrent cervical cancer]. [2018]

5. Japan pubmed.ncbi.nlm.nih.gov

[Promising new drugs for gynecological cancer]. [2018]

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

Irinotecan for the treatment of cervical cancer. [2018]

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

Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. [2018]

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

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

9. Spain pubmed.ncbi.nlm.nih.gov

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

10. 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]

11. Japan pubmed.ncbi.nlm.nih.gov

Feasibility study on combination chemotherapy using nogitecan hydrochloride (topotecan) and cisplatin for patients with metastatic, persistent, or recurrent uterine cervical cancer. [2018]