A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)

NCT ID: NCT03657043

Last Updated: 2023-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-20
• Study Completion Date: 2022-02-08

Brief Summary

This trial will study tisotumab vedotin to find out what its side effects are and to see if it works for platinum-resistant ovarian cancer (PROC). It will test different doses of tisotumab vedotin that are given at different times. It will also compare the side effects and ability to treat tumors of these different doses and schedules. In this study, there will be a safety run-in group of approximately 12 patients that will look at a dose-dense treatment schedule. In a dose-dense schedule, smaller doses are given more frequently. In addition to the safety run-in patients, there will be three groups in the study. One group will get tisotumab vedotin once every 3 weeks (21-day cycles). The two other groups will get tisotumab vedotin once a week for 3 weeks followed by 1 week off (28-day cycles).

Detailed Description

The study objectives are to evaluate the safety, antitumor activity, and pharmacokinetics of tisotumab vedotin (TV) administered every 3 weeks or on Days 1, 8, and 15 of every 4-week cycle (3Q4W) for patients with epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has relapsed within 6 months of the completion of platinum-based treatment and determined to be platinum resistant. All patients must have PROC and be eligible for single agent chemotherapy.

The safety run-in period will evaluate the safety of a weekly schedule. The highest dose level that is considered safe will be the recommended phase 2 dose (RP2D) and will be used in Part A. In Part A, participants will be randomized in a 1:1 ratio to receive tisotumab vedotin intravenously (IV) every 3 weeks (Q3W regimen) or the safety run-in RP2D on Days 1, 8, and 15 of every 4-week cycle (weekly regimen; 3Q4W) if a RP2D has been identified. Participants who enroll in Part B will receive tisotumab vedotin on Days 1, 8, and 15 of every 4-week cycle (weekly regimen) at a pre-specified dose level, if the dose level is considered safe and tolerable in the safety run-in period.

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Safety Run-In (3Q4W Schedule)

28-day, 3 dose cycle

Group Type: EXPERIMENTAL

tisotumab vedotin

Intervention Type: DRUG

Intravenous (IV) infusion

Part A: Tisotumab Vedotin

21-day, single dose cycle

Group Type: EXPERIMENTAL

tisotumab vedotin

Intervention Type: DRUG

Intravenous (IV) infusion

Part A: Tisotumab Vedotin (3Q4W Schedule)

28-day, 3 dose cycle

Group Type: EXPERIMENTAL

tisotumab vedotin

Intervention Type: DRUG

Intravenous (IV) infusion

Part B: Tisotumab Vedotin (3Q4W Schedule)

28-day, 3 dose cycle

Group Type: EXPERIMENTAL

tisotumab vedotin

Intervention Type: DRUG

Intravenous (IV) infusion

Interventions

tisotumab vedotin

Intravenous (IV) infusion

Intervention Type: DRUG

Other Intervention Names

TIVDAK

Eligibility Criteria

Inclusion Criteria

• Histologic documentation of epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer
• Safety run-in only: PROC. Patients may have received more than 1 prior systemic treatment regimen in the PROC setting.
• Part A and Part B only: Patients with PROC who have received 1 to 3 anticancer lines of therapy overall, including at least 1 line of therapy containing bevacizumab or biosimilar.

• Adjuvant ± neoadjuvant are considered 1 line of therapy.
• Patients may have received a PARP inhibitor or an immuno-oncology (IO) agent; any of these regimens are to be considered a line of therapy for the purposes of this study if not used as maintenance therapy.
• Maintenance therapy (including bevacizumab, PARP inhibitors and IOs) will be considered part of the preceding line of therapy and not to be counted as a new line of therapy.
• Any chemotherapy regimen change due to toxicity in the absence of disease progression is considered as part of the same line of therapy.
• Hormonal therapy will be not be counted towards the lines of therapy.
• Measurable disease according to RECIST v1.1 as assessed by the investigator
• An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Life expectancy of at least 3 months
• Able to provide fresh or archival tissue for biomarker analysis

Exclusion Criteria

• Primary platinum-refractory disease, defined as disease progression within 2 months of completion of first line platinum-based therapy
• Patients with clinical symptoms or signs of gastrointestinal obstruction with the past 6 months or who currently require parenteral nutrition
• Hematological: Known past or current coagulation defects leading to an increased risk of bleeding, diffuse alveolar hemorrhage from vasculitis, known bleeding diathesis, ongoing major bleeding, or trauma with increased risk of life-threatening bleeding within 8 weeks of trial entry
• Cardiovascular: Clinically significant cardiac disease including uncontrolled hypertension, unstable angina, acute myocardial infarction with 6 months of screening, serious cardiac arrhythmia requiring medication, medical history of congestive heart failure, or medical history of decreased cardiac ejection fraction of <45%
• Ophthalmological: Active ocular surface disease at baseline or prior episode of cicatricial conjunctivitis or Stevens Johnson syndrome
• Prior treatment with MMAE-derived drugs
• Inflammatory bowel disease including Crohn's disease and ulcerative colitis
• Ongoing, acute, or chronic inflammatory skin disease
• Uncontrolled tumor-related pain
• Inflammatory lung disease requiring chronic medical therapy
• Grade 3 or higher pulmonary disease unrelated to underlying malignancy
• Uncontrolled pleural or pericardial effusions
• Grade >1 peripheral neuropathy
• Patients who are pregnant or breastfeeding

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Genmab

INDUSTRY

Sponsor Role: collaborator

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kristi Schmidt, MD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

Stanford Cancer Center South Bay

San Jose, California, United States

Poudre Valley Health System (PVHS)

Fort Collins, Colorado, United States

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States

Miami Cancer Institute- Plantation (MCIP)

Miami, Florida, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Augusta University

Augusta, Georgia, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, United States

University of Missouri Healthcare / Ellis Fischel Cancer Center

Columbia, Missouri, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Mount Sinai Chelsea

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, United States

Cleveland Clinic, The

Cleveland, Ohio, United States

Ohio State University Clinical Trials Management Office

Columbus, Ohio, United States

Cleveland Clinic Hillcrest Hospital

Mayfield Heights, Ohio, United States

Texas Oncology - Fort Worth

Dallas, Texas, United States

Renovatio Clinical

The Woodlands, Texas, United States

University of Virginia

Charlottesville, Virginia, United States

Algemeen Ziekenhuis Maria Middelares

Ghent, Other, Belgium

Universitair Ziekenhuis Leuven

Lueven, Other, Belgium

Aalborg Universite Hospital

Aalborg, Other, Denmark

Mater Private

Dublin, Other, Ireland

Cork University Hospital

Wilton, Other, Ireland

Ospedale Ramazzini di Carpi

Carpi, Other, Italy

IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l

Meldola, Other, Italy

Istituto Europeo di Oncologia

Milan, Other, Italy

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, Other, Italy

Fondazione Policlinico Universitario Agostino

Rome, Other, Italy

Hospital Universitario Vall d'Hebron

Barcelona, Other, Spain

L'Institut Catala d'Oncologia

L'Hospitalet de Llobregat, Other, Spain

Hospital Universitario Ramon y Cajal

Madrid, Other, Spain

HM Centro Integral Oncologico Clara Campal

Madrid, Other, Spain

Clinica Universidad de Navarra

Pamplona, Other, Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Other, Spain

Countries

United States; Belgium; Denmark; Ireland; Italy; Spain

References

Feng S, Gunawan R, Passey C, Voellinger J, Polhamus D, Gerritsen A, O'Day C, Carret AS, Soumaoro I, Gupta M, Hanley WD. Exposure-safety Markov modeling of ocular adverse events in patient populations treated with tisotumab vedotin. J Pharmacokinet Pharmacodyn. 2025 Oct 3;52(5):55. doi: 10.1007/s10928-025-10003-w.

Reference Type: DERIVED

PMID: 41044356 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

SGNTV-002

Identifier Type: -

Identifier Source: org_study_id