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

NCT03657043 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: SGNTV-002
• Study Type: interventional
• Target: 98
• Locations: 6 countries
• Sites: 37

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).

Conditions

Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer

Keywords

Platinum-resistant; Antibody drug conjugate; Tisotumab vedotin; PROC; Seattle Genetics

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only)

  Incidence of dose-limiting toxicity (DLT) was evaluated in participants enrolled in the Safety Run-In, who were followed for protocol-defined DLT events up to 28 days after the first dose of tisotumab vedotin.

  Up to 28 days

• Confirmed Objective Response Rate (ORR) (Part B)

  Proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

  Up to 9.7 months

Secondary Outcomes (20)

• Number of Participants With Adverse Events (AEs) (Part B)

  Up to 23.0 months

• Confirmed and Unconfirmed ORR (Part B)

  Up to 9.7 months

• Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B)

  Up to 10.1 months

• Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B)

  Up to 10.1 months

• Duration of Response (DOR) (Part B)

  Up to 8.3 months

Study Arms (4)

Safety Run-In (3Q4W Schedule)

EXPERIMENTAL

28-day, 3 dose cycle

Drug: tisotumab vedotin

Part A: Tisotumab Vedotin

EXPERIMENTAL

21-day, single dose cycle

Drug: tisotumab vedotin

Part A: Tisotumab Vedotin (3Q4W Schedule)

EXPERIMENTAL

28-day, 3 dose cycle

Drug: tisotumab vedotin

Part B: Tisotumab Vedotin (3Q4W Schedule)

EXPERIMENTAL

28-day, 3 dose cycle

Drug: tisotumab vedotin

Interventions

tisotumab vedotin DRUG

Intravenous (IV) infusion

Also known as: TIVDAK

Part A: Tisotumab Vedotin; Part A: Tisotumab Vedotin (3Q4W Schedule); Part B: Tisotumab Vedotin (3Q4W Schedule); Safety Run-In (3Q4W Schedule)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead
• Genmab: collaborator

Study Sites (37)

Stanford Cancer Center South Bay

San Jose, California, 95124, United States

Location

Poudre Valley Health System (PVHS)

Fort Collins, Colorado, 80524, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

Miami Cancer Institute- Plantation (MCIP)

Miami, Florida, 33176, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

University of Missouri Healthcare / Ellis Fischel Cancer Center

Columbia, Missouri, 65212, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai Chelsea

New York, New York, 10011, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic, The

Cleveland, Ohio, 44195, United States

Location

Ohio State University Clinical Trials Management Office

Columbus, Ohio, 43210, United States

Location

Cleveland Clinic Hillcrest Hospital

Mayfield Heights, Ohio, 44124, United States

Location

Texas Oncology - Fort Worth

Dallas, Texas, 75246, United States

Location

Renovatio Clinical

The Woodlands, Texas, 77380, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Algemeen Ziekenhuis Maria Middelares

Ghent, Other, 9000, Belgium

Location

Universitair Ziekenhuis Leuven

Lueven, Other, 3000, Belgium

Location

Aalborg Universite Hospital

Aalborg, Other, 9100, Denmark

Location

Mater Private

Dublin, Other, D07 WKW8, Ireland

Location

Cork University Hospital

Wilton, Other, T12 E8YV, Ireland

Location

Ospedale Ramazzini di Carpi

Carpi, Other, 41012, Italy

Location

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

Meldola, Other, 47014, Italy

Location

Istituto Europeo di Oncologia

Milan, Other, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale

Napoli, Other, 80131, Italy

Location

Fondazione Policlinico Universitario Agostino

Rome, Other, 00168, Italy

Location

Hospital Universitario Vall d'Hebron

Barcelona, Other, 08035, Spain

Location

L'Institut Catala d'Oncologia

L'Hospitalet de Llobregat, Other, 08907, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, Other, 28034, Spain

Location

HM Centro Integral Oncologico Clara Campal

Madrid, Other, 28050, Spain

Location

Clinica Universidad de Navarra

Pamplona, Other, 31008, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Other, 28223, Spain

Location

Related Publications (1)

• 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.

  PMID: 41044356 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

tisotumab vedotin

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seagen Inc.

medinfo@seagen.com

(855) 473-2436

Study Officials

• Kristi Schmidt, MD

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2018
• First Posted: September 4, 2018
• Study Start: March 20, 2019
• Primary Completion: February 8, 2022
• Study Completion: February 8, 2022
• Last Updated: May 6, 2023
• Results First Posted: May 6, 2023

Record last verified: 2023-04

Locations

DK (1); ES (6); IT (5); US (21); IE (2); BE (2)