Clinical trial NCT03657043: A Study of Weekly Tisotumab Vedotin for Patients With Platinum-Resistant Ovarian Cancer With Safety Run-in (innovaTV 208)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Keywords: Platinum-resistant
Antibody drug conjugate
Tisotumab vedotin
PROC
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genmab
First posted: 2018-09-04
Enrollment: 98
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs) (Safety Run-In Only)
timeFrame: Up to 28 days
measure: Confirmed Objective Response Rate (ORR) (Part B)
timeFrame: Up to 9.7 months
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs) (Part B)
timeFrame: Up to 23.0 months
measure: Confirmed and Unconfirmed ORR (Part B)
timeFrame: Up to 9.7 months
measure: Cancer Antigen 125 (CA-125) Response Rate According to Gynecologic Cancer Intergroup (GCIG) Criteria (Part B)
timeFrame: Up to 10.1 months
measure: Overall Response According to the Gynecological Cancer Intergroup (GCIG) Combined RECIST and CA-125 Criteria (Part B)
timeFrame: Up to 10.1 months
measure: Duration of Response (DOR) (Part B)
timeFrame: Up to 8.3 months
measure: Disease Control Rate (DCR) (Part B)
timeFrame: Up to 3.0 months
measure: Time to Response (TTR) (Part B)
timeFrame: Up to 23.0 months
measure: Progression-free Survival (PFS) (Part B)
timeFrame: Up to 9.7 months
measure: Overall Survival (OS) (Part B)
timeFrame: Up to 23.0 months
measure: Incidence of Antitherapeutic Antibodies (ATA) (Part B)
timeFrame: Up to 6.9 months
measure: Pharmacokinetic (PK) Parameter: Antibody-Drug Conjugate (ADC) Maximum Concentration (Cmax) (Part B)
timeFrame: 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.
measure: PK Parameter: ADC Time of Cmax (Tmax) (Part B)
timeFrame: 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.
measure: PK Parameter: ADC Area Under Concentration-Time Curve (AUC) (Part B)
timeFrame: 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).
measure: PK Parameter: Free Monomethyl Auristatin E (MMAE) Cmax (Part B)
timeFrame: 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.
measure: PK Parameter: MMAE Tmax (Part B)
timeFrame: 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.
measure: PK Parameter: MMAE AUC (Part B)
timeFrame: 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.
measure: PK Parameter: MMAE Trough Concentration (Ctrough) (Part B)
timeFrame: 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.
measure: PK Parameter: Total Antibody (TAb) Cmax (Part B)
timeFrame: 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.
measure: PK Parameter: TAb Tmax (Part B)
timeFrame: 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.
measure: PK Parameter: TAb Area Under Concentration-Time Curve (AUC) (Part B)
timeFrame: 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).
Other outcomes:
Locations:
city: San Jose
country: United States
facility: Stanford Cancer Center South Bay
state: California
city: Fort Collins
country: United States
facility: Poudre Valley Health System (PVHS)
state: Colorado
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute- Plantation (MCIP)
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Columbia
country: United States
facility: University of Missouri Healthcare / Ellis Fischel Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Mount Sinai Chelsea
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, The
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Clinical Trials Management Office
state: Ohio
city: Mayfield Heights
country: United States
facility: Cleveland Clinic Hillcrest Hospital
state: Ohio
city: Dallas
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Ghent
country: Belgium
facility: Algemeen Ziekenhuis Maria Middelares
state: Other
city: Lueven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Other
city: Aalborg
country: Denmark
facility: Aalborg Universite Hospital
state: Other
city: Dublin
country: Ireland
facility: Mater Private
state: Other
city: Wilton
country: Ireland
facility: Cork University Hospital
state: Other
city: Carpi
country: Italy
facility: Ospedale Ramazzini di Carpi
state: Other
city: Meldola
country: Italy
facility: IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
state: Other
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia
state: Other
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
state: Other
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: L'Institut Catala d'Oncologia
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
state: Other
city: Madrid
country: Spain
facility: HM Centro Integral Oncologico Clara Campal
state: Other
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Other
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Other
Study officials:
affiliation: Seagen Inc.
name: Kristi Schmidt, MD
role: STUDY_DIRECTOR
References: