Tisotumab Vedotin for Cancer

(innovaTV 207 Trial)

Recruiting at 78 trial locations

Overseen By Seagen Trial Information Support

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Seagen Inc.

Must not be taking: Systemic steroids

Disqualifiers: Neuroendocrine, Sarcomatoid, Active bleeding, others

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

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

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 3 years

352 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it is common for clinical trials to have restrictions on certain medications, especially those that might interfere with the study drug. It's best to discuss your current medications with the trial coordinators.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the idea that Tisotumab Vedotin for Cancer is an effective drug?

The available research shows that Tisotumab Vedotin has been granted accelerated approval in the USA for treating adults with recurrent or metastatic cervical cancer, especially when the disease progresses after chemotherapy. Clinical trials have shown that it can lead to significant and lasting remission in patients who are difficult to treat. This suggests that Tisotumab Vedotin is an effective option for these patients. ^{1 2 3 4 5}

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

Tisotumab Vedotin has been shown to be effective in treating recurrent or metastatic cervical cancer, as it targets a protein called tissue factor on cancer cells and delivers a cancer-killing agent directly to them. It has received accelerated approval in the USA based on a phase II trial, indicating it can lead to significant and lasting remission in patients who have not responded to other treatments. ^{1 2 3 4 5}

What safety data is available for Tisotumab Vedotin and related treatments?

The provided research does not contain specific safety data for Tisotumab Vedotin or its related names such as Tivdak, Tisotumab vedotin-tftv, HuMax-TF-ADC, or TF-011-MMAE. The studies mentioned focus on other drugs and treatments, such as ST-1968, avapritinib, panitumumab, raltitrexed, and targeted agents for colorectal cancer, none of which are directly related to Tisotumab Vedotin. Therefore, no relevant safety data for Tisotumab Vedotin is available in the provided research. ^{6 7 8 9 10}

Is the drug Tisotumab Vedotin a promising treatment for cancer?

Yes, Tisotumab Vedotin is a promising drug for treating cancer, especially for patients with cervical cancer that has come back or spread after chemotherapy. It targets cancer cells directly, helping to shrink tumors and improve patient outcomes. The drug has received accelerated approval in the USA, indicating its potential effectiveness. ^{1 2 3 5 11}

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 cytotoxic agent directly into the tumor cells. This targeted approach is different from traditional chemotherapy and immunotherapy, offering a novel treatment option for patients with recurrent or metastatic cervical cancer. ^{1 2 3 5 11}

What is the purpose of this trial?

This trial will study tisotumab vedotin to find out whether it is an effective treatment alone or with other anticancer drugs for certain solid tumors and what side effects (unwanted effects) may occur. There are seven parts to this study. * In Part A, the treatment will be given to participants every 3 weeks (3-week cycles). * In Part B, participants will receive tisotumab vedotin on Days 1, 8, and 15 every 4-week cycle. * In Part C, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle. * In Part D, participants will be given treatment on Day 1 of every 3-week cycle. Participants in Part D will get tisotumab vedotin with either: * Pembrolizumab or, * Pembrolizumab and carboplatin, or * Pembrolizumab and cisplatin * In Part E, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle. * In Part F, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part F will get tisotumab vedotin with pembrolizumab. * In Part G, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part G will get tisotumab vedotin with pembrolizumab and carboplatin.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for patients with certain solid tumors like colorectal, pancreatic, and non-small cell lung cancer who have seen their disease progress after treatment. They must have tried specific therapies depending on the type of cancer and can't be candidates for standard therapy. Participants need a performance status score of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory.

Inclusion Criteria

I have colorectal cancer and have been treated with specific drugs but no more than 3 times for advanced disease.

I have taken a tyrosine kinase inhibitor and had no more than 4 treatments for my metastatic condition.

I have pancreatic cancer and have had only one treatment for it when it could not be surgically removed.

Exclusion Criteria

I have lung disease but don't need steroids or long-term oxygen.

I have or had another type of cancer besides the one I am seeking treatment for.

I have pain from my cancer that isn't relieved by treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tisotumab vedotin alone or in combination with other anticancer drugs in various schedules across seven parts of the study

Up to 3 years

Visits every 3 to 6 weeks depending on the part

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Pembrolizumab
• Tisotumab Vedotin

Trial Overview The study tests tisotumab vedotin alone or combined with pembrolizumab and/or platinum-based chemotherapy (carboplatin or cisplatin) across seven parts with varying schedules. It aims to determine effectiveness against solid tumors and identify potential side effects from these treatments.

Participant Groups

Group I: Part G: Tisotumab Vedotin Combination Therapy - Q2W Schedule Experimental Treatment 3 Interventions

Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting

Group II: Part F: Tisotumab Vedotin Combination Therapy - Q2W Schedule Experimental Treatment 2 Interventions

Tisotumab Vedotin + pembrolizumab. Tisotumab Vedotin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting

Group III: Part E: Tisotumab Vedotin - 2Q4W Schedule Experimental Treatment 1 Intervention

Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC in the second- or third-line setting

Group IV: Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule Experimental Treatment 4 Interventions

Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC

Group V: Part C: Tisotumab Vedotin - 2Q4W Schedule Experimental Treatment 1 Intervention

Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC or sqNSCLC in 2L+

Group VI: Part B: Tisotumab Vedotin - 3Q4W Schedule Experimental Treatment 1 Intervention

Tisotumab Vedotin on Days 1, 8, and 15 of 28-day cycle in participants with various solid tumors in 2L+

Group VII: Part A: Tisotumab Vedotin - Q3W Schedule Experimental Treatment 1 Intervention

Tisotumab Vedotin on Day 1 of every 21-day cycle in participants with various solid tumors in 2L+

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 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

Seagen, a wholly owned subsidiary of Pfizer

Lead Sponsor

Trials

20

Recruited

4,900+

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

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 (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-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, an antibody-drug conjugate targeting tissue factor, demonstrated a manageable safety profile in a study involving 174 patients with advanced solid tumors, with a recommended dose of 2.0 mg/kg established after observing dose-limiting toxicities at higher doses.

The treatment showed preliminary antitumor activity, with a confirmed objective response rate of 15.6% across various tumor types, indicating potential effectiveness in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. de Bono, JS., Concin, N., Hong, DS., et al.[2020]

Tisotumab vedotin is an antibody-drug conjugate that received accelerated FDA approval for treating recurrent or metastatic cervical cancer, showing a 24% objective response rate in a study of 101 patients.

While it demonstrates clinical efficacy, tisotumab vedotin is associated with significant adverse events, including ocular toxicity and peripheral neuropathy, with 92% of patients experiencing treatment-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the novel tissue factor antibody-drug conjugate: Tisotumab vedotin. Luu, K., Chu, A., Chang, B.[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]

In a phase I study involving 63 patients, the new drug namitecan was found to have a maximum tolerated dose of 15 mg when given twice in three weeks and 23 mg when given once every three weeks, with neutropenia being the main dose-limiting toxicity.

Namitecan showed promising preliminary antitumor activity, with two patients experiencing partial remission, and demonstrated favorable pharmacokinetics, indicating it could be a safe and effective treatment option for patients with advanced solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors. Joerger, M., Hess, D., Delmonte, A., et al.[2018]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a study of 463 patients with metastatic colorectal cancer, those treated with panitumumab who experienced more severe skin toxicity had significantly longer overall survival and progression-free survival compared to those with less severe toxicity.

The severity of skin toxicity, as measured by patient-reported outcomes, was inversely related to health-related quality of life scores, indicating that while skin toxicity can be bothersome, it may correlate with better treatment outcomes, especially in patients with wild-type KRAS tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. Peeters, M., Siena, S., Van Cutsem, E., et al.[2018]

Raltitrexed is an effective treatment for advanced colorectal cancer, showing similar efficacy to the standard combination therapy of 5-fluorouracil and leucovorin, based on Phase III studies.

Patients treated with raltitrexed experienced fewer severe side effects compared to those on 5-FU + LV, making it a better-tolerated alternative for cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Raltitrexed (Tomudex). Van Cutsem, E.[2019]

In a systematic review of eight randomized controlled trials involving targeted therapies for RAS wild-type metastatic colon cancer, bevacizumab was associated with a significantly higher risk of serious hypertension, while panitumumab showed a markedly elevated risk of serious thromboembolism (RR 3.65).

Panitumumab-based chemotherapy also presented a higher risk of serious dermatological and renal toxicities compared to cetuximab, including skin toxicity (RR 15.22), mucositis (RR 3.18), hypomagnesemia (RR 20.10), and dehydration (RR 2.81).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis. Choi, YJ., Choi, CY., Rhie, SJ., et al.[2023]

Tisotumab vedotin, an investigational antibody-drug conjugate for treating recurrent or metastatic cervical cancer, has a pharmacokinetic profile characterized by a two-compartment model, with a median terminal half-life of 4.04 days for the ADC and 2.56 days for the MMAE component, based on data from 399 patients.

Body weight significantly influences the distribution and elimination of tisotumab vedotin, supporting the use of weight-based dosing, while the presence of antidrug antibodies in 3.3% of patients did not impact the pharmacokinetic parameters.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic analysis for tisotumab vedotin in patients with locally advanced and/or metastatic solid tumors. Gibiansky, L., Passey, C., Voellinger, J., et al.[2023]

References

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

Tisotumab Vedotin: First Approval. [2022]

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

New Drug Treats Cervical Cancer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Tisotumab vedotin in patients with advanced or metastatic solid tumours (InnovaTV 201): a first-in-human, multicentre, phase 1-2 trial. [2020]

4. England pubmed.ncbi.nlm.nih.gov

A review of the novel tissue factor antibody-drug conjugate: Tisotumab vedotin. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

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

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

Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors. [2018]

7. England pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. [2023]

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

Association of progression-free survival, overall survival, and patient-reported outcomes by skin toxicity and KRAS status in patients receiving panitumumab monotherapy. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Raltitrexed (Tomudex). [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis. [2023]

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

Population pharmacokinetic analysis for tisotumab vedotin in patients with locally advanced and/or metastatic solid tumors. [2023]