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

Sponsor

Seagen Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03657043

Collaborator

Genmab (Industry)

Enrollment

Locations

Arms

34.7

Actual Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer Fallopian Tube Cancer Peritoneal Cancer	Drug: tisotumab vedotin	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

98 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 20, 2019

Actual Primary Completion Date :

Feb 8, 2022

Actual Study Completion Date :

Feb 8, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicities (DLTs) (Safety Run-in only) [Up to 28 days]
Confirmed objective response rate (ORR) (Parts A and B) [Up to 3 years]
Proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the investigator

Secondary Outcome Measures

Incidence of adverse events that are Grade 3+, treatment-related, or serious (Parts A and B) [Up to 3 years]
Confirmed and unconfirmed ORR (Parts A and B) [Up to 3 years]
Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
Cancer Antigen 125 (CA-125) response rate according to Gynecologic Cancer Intergroup (GCIG) criteria (Parts A and B) [Up to 3 years]
Proportion of patients who have at least a 50% reduction in CA-125 value from baseline
Overall response according to the Gynecological Cancer Intergroup (GCIG) combined RECIST and CA-125 criteria (Parts A and B) [Up to 3 years]
Proportion of patients whose best response is a CR or PR according to the GCIG combined RECIST and CA-125 criteria
Duration of response (DOR) (Parts A and B) [Up to 3 years]
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
Disease control rate (DCR) (Parts A and B) [Up to 3 years]
Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD)
Time to response (TTR) (Parts A and B) [Up to 3 years]
Time from the start of study treatment to the first documentation of objective response (CR or PR that is subsequently confirmed)
Progression-free survival (PFS) (Parts A and B) [Up to 3 years]
Time from the start of study treatment to the first documentation of PD or death due to any cause, whichever comes first
Overall survival (OS) (Parts A and B) [Up to 3 years]
Time from the start of study treatment to date of death due to any cause
Pharmacokinetic (PK) parameter: Cmax (Parts A and B) [Up to 3 years]
Maximum observed concentration
PK parameter: AUClast (Parts A and B) [Up to 3 years]
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
Incidence of antitherapeutic antibodies (ATA) (Parts A and B) [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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