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

Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03657043
• Other study ID #: SGNTV-002
• Status: Completed
• Phase: Phase 2
• Start date: March 20, 2019
• Est. completion date: February 8, 2022

Study information

• Verified date: April 2023
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: February 8, 2022
• Est. primary completion date: February 8, 2022
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Cancer
• Fallopian Tube Neoplasms
• Ovarian Cancer
• Ovarian Neoplasms
• Peritoneal Cancer

Intervention

Drug:
• tisotumab vedotin
Intravenous (IV) infusion

Locations

Country	Name	City	State
Belgium	Algemeen Ziekenhuis Maria Middelares	Ghent	Other
Belgium	Universitair Ziekenhuis Leuven	Lueven	Other
Denmark	Aalborg Universite Hospital	Aalborg	Other
Ireland	Mater Private	Dublin	Other
Ireland	Cork University Hospital	Wilton	Other
Italy	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	Milano	Other
Italy	Istituto Nazionale Tumori IRCCS Fondazione G. Pascale	Napoli	Other
Italy	Fondazione Policlinico Universitario Agostino	Rome	Other
Spain	Hospital Universitario Vall d'Hebron	Barcelona	Other
Spain	L'Institut Catala d'Oncologia	L'Hospitalet de Llobregat	Other
Spain	HM Centro Integral Oncologico Clara Campal	Madrid	Other
Spain	Hospital Universitario Ramon y Cajal	Madrid	Other
Spain	Clinica Universidad de Navarra	Pamplona	Other
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcón	Other
United States	Augusta University	Augusta	Georgia
United States	University of Virginia	Charlottesville	Virginia
United States	Cleveland Clinic Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic, The	Cleveland	Ohio
United States	University of Missouri Healthcare / Ellis Fischel Cancer Center	Columbia	Missouri
United States	Ohio State University Clinical Trials Management Office	Columbus	Ohio
United States	Texas Oncology - Fort Worth	Dallas	Texas
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Poudre Valley Health System (PVHS)	Fort Collins	Colorado
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Cleveland Clinic Hillcrest Hospital	Mayfield Heights	Ohio
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Miami Cancer Institute- Plantation (MCIP)	Miami	Florida
United States	Columbia University Medical Center	New York	New York
United States	Mount Sinai Chelsea	New York	New York
United States	Mount Sinai Medical Center	New York	New York
United States	Stanford Cancer Center South Bay	San Jose	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Renovatio Clinical	The Woodlands	Texas
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Seagen Inc.	Genmab

Countries where clinical trial is conducted

United States,  Belgium,  Denmark,  Ireland,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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).
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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).