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

Open Label Phase 2 Study of Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With a Safety Run-in of a Dose-Dense Regimen

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).

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cancer
• Intervention / Treatment: Drug: tisotumab vedotin

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Other
    • Ghent, Other, Belgium, 9000
      • Algemeen Ziekenhuis Maria Middelares
    • Lueven, Other, Belgium, 3000
      • Universitair Ziekenhuis Leuven
• Denmark
  • Other
    • Aalborg, Other, Denmark, 9100
      • Aalborg Universite Hospital
• Ireland
  • Other
    • Dublin, Other, Ireland, D07 WKW8
      • Mater Private
    • Wilton, Other, Ireland, T12 E8YV
      • Cork University Hospital
• Italy
  • Other
    • Carpi, Other, Italy, 41012
      • Ospedale Ramazzini di Carpi
    • Meldola, Other, Italy, 47014
      • IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
    • Milano, Other, Italy, 20141
      • Istituto Europeo di Oncologia
    • Napoli, Other, Italy, 80131
      • Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
    • Rome, Other, Italy, 00168
      • Fondazione Policlinico Universitario Agostino
• Spain
  • Other
    • Barcelona, Other, Spain, 08035
      • Hospital Universitario Vall d'Hebron
    • L'Hospitalet de Llobregat, Other, Spain, 08907
      • L'Institut Catala d'Oncologia
    • Madrid, Other, Spain, 28034
      • Hospital Universitario Ramon y Cajal
    • Madrid, Other, Spain, 28050
      • HM Centro Integral Oncologico Clara Campal
    • Pamplona, Other, Spain, 31008
      • Clinica Universidad de Navarra
    • Pozuelo de Alarcón, Other, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
• United States
  • California
    • San Jose, California, United States, 95124
      • Stanford Cancer Center South Bay
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Health System (PVHS)
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute- Plantation (MCIP)
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Augusta, Georgia, United States, 30912
      • Augusta University
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute / Wayne State University
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri Healthcare / Ellis Fischel Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10011
      • Mount Sinai Chelsea
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic, The
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Clinical Trials Management Office
    • Mayfield Heights, Ohio, United States, 44124
      • Cleveland Clinic Hillcrest Hospital
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Fort Worth
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-In (3Q4W Schedule); 28-day, 3 dose cycle	Drug: tisotumab vedotin; Intravenous (IV) infusion; Other Names: TIVDAK
Experimental: Part A: Tisotumab Vedotin; 21-day, single dose cycle	Drug: tisotumab vedotin; Intravenous (IV) infusion; Other Names: TIVDAK
Experimental: Part A: Tisotumab Vedotin (3Q4W Schedule); 28-day, 3 dose cycle	Drug: tisotumab vedotin; Intravenous (IV) infusion; Other Names: TIVDAK
Experimental: Part B: Tisotumab Vedotin (3Q4W Schedule); 28-day, 3 dose cycle	Drug: tisotumab vedotin; Intravenous (IV) infusion; Other Names: TIVDAK

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs) (Part B)	An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment.	Up to 23.0 months
Confirmed and Unconfirmed ORR (Part B)	Proportion of participants who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator	Up to 9.7 months
Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B)	Percentage of participants who have at least a 50% reduction in CA-125 value from baseline	Up to 10.1 months
Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B)	Percentage of participants whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria	Up to 10.1 months
Duration of Response (DOR) (Part B)	Time from the first documentation of objective response (CR or PR that is subsequently confirmed) to the first documentation of PD or death due to any cause, whichever comes first	Up to 8.3 months
Disease Control Rate (DCR) (Part B)	Percentage of participants who achieved a confirmed Complete Response(CR) or Partial Response (PR) per RECIST v1.1 as assessed by the investigator, or meet the Stable Disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks.	Up to 3.0 months
Time to Response (TTR) (Part B)	Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)	Up to 23.0 months
Progression-free Survival (PFS) (Part B)	Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first	Up to 9.7 months
Overall Survival (OS) (Part B)	Time from the start of study treatment to date of death due to any cause	Up to 23.0 months
Incidence of Antitherapeutic Antibodies (ATA) (Part B)	The proportion of participants who develop ATA at any time during the study. A positive baseline ATA result is considered positive post-baseline if the post-baseline ATA titer result is at least four times higher than the baseline result.	Up to 6.9 months
Pharmacokinetic (PK) Parameter: Antibody-Drug Conjugate (ADC) Maximum Concentration (Cmax) (Part B)	ADC Cmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: ADC Time of Cmax (Tmax) (Part B)	ADC Tmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: ADC Area Under Concentration-Time Curve (AUC) (Part B)	ADC AUC was derived from the PK blood samples collected.	Cycle 1 Dose 1 AUC 7: Assessed from Cycle 1 Days 1 - 8 (predose). Cycle 1 Dose 3 AUC 7: Assessed from Cycle 1 Days 15 - 22. Cycle 1 Dose 3 AUC 14: Assessed from Cycle 1 Days 15 - Cycle 2 Day 1 (predose).
PK Parameter: Free Monomethyl Auristatin E (MMAE) Cmax (Part B)	MMAE Cmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: MMAE Tmax (Part B)	MMAE Tmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: MMAE AUC (Part B)	MMAE AUC was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: MMAE Trough Concentration (Ctrough) (Part B)	MMAE Ctrough was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: Total Antibody (TAb) Cmax (Part B)	TAb Cmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: TAb Tmax (Part B)	TAb Tmax was derived from the PK blood samples collected.	Samples for PK measures were collected at Cycle 1 Day 1 (predose, end of infusion, 1 hr, and 5 hr), Day 3, Day 8 (predose), Day 15 (predose, end of infusion, 1 hr, and 5 hr), Day 17, Day 22, and Cycle 2 Day 1 (predose). Approximately 4 weeks per cycle.
PK Parameter: TAb Area Under Concentration-Time Curve (AUC) (Part B)	TAb AUC was derived from the PK blood samples collected.	Cycle 1 Dose 1 AUC 7: Assessed from Cycle 1 Days 1 - 8 (predose). Cycle 1 Dose 3 AUC 7: Assessed from Cycle 1 Days 15 - 22. Cycle 1 Dose 3 AUC 14: Assessed from Cycle 1 Days 15 - Cycle 2 Day 1 (predose).

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Collaborators: Genmab

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2019
• Primary Completion (Actual): February 8, 2022
• Study Completion (Actual): February 8, 2022

Study Registration Dates

• First Submitted: August 22, 2018
• First Submitted That Met QC Criteria: August 30, 2018
• First Posted (Actual): September 4, 2018

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 13, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Platinum-resistant; Seattle Genetics; Antibody drug conjugate; PROC; Tisotumab vedotin
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tisotumab vedotin
• Other Study ID Numbers: SGNTV-002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No