Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors
- Conditions
- Colorectal NeoplasmsExocrine Pancreatic CancerCarcinoma, Non-Small-Cell LungCarcinoma, Squamous Cell of Head and Neck
- Interventions
- Registration Number
- NCT03485209
- Lead Sponsor
- Seagen, a wholly owned subsidiary of Pfizer
- Brief Summary
This trial will study tisotumab vedotin to find out whether it is an effective treatment alone or with other anticancer drugs for certain solid tumors and what side effects (unwanted effects) may occur. There are seven parts to this study.
* In Part A, the treatment will be given to participants every 3 weeks (3-week cycles).
* In Part B, participants will receive tisotumab vedotin on Days 1, 8, and 15 every 4-week cycle.
* In Part C, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle.
* In Part D, participants will be given treatment on Day 1 of every 3-week cycle. Participants in Part D will get tisotumab vedotin with either:
* Pembrolizumab or,
* Pembrolizumab and carboplatin, or
* Pembrolizumab and cisplatin
* In Part E, participants will receive tisotumab vedotin on Days 1 and 15 of every 4-week cycle.
* In Part F, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part F will get tisotumab vedotin with pembrolizumab.
* In Part G, participants will receive tisotumab vedotin on Days 1, 15, and 29 of every 6-week cycle. Participants in Part G will get tisotumab vedotin with pembrolizumab and carboplatin.
- Detailed Description
The primary goal of this trial is to assess the activity, safety, and tolerability of tisotumab vedotin for the treatment of selected solid tumors. Patients will be treated with single agent tisotumab vedotin or tisotumab vedotin in combination with other anticancer agents. Patients who meet eligibility criteria will be enrolled into cohorts based on tumor type. Tumor types to be evaluated include colorectal cancer, squamous non-small cell lung cancer (sqNSCLC), exocrine pancreatic adenocarcinoma, and head and neck squamous cell carcinoma (HNSCC).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 352
-
Parts A, B, and C
-
Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, sqNSCLC, or HNSCC participants who are not candidates for standard therapy.
-
All participants must have experienced disease progression on or after their most recent systemic therapy.
-
Colorectal cancer (closed to enrollment): participants must have received prior therapy with each of following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Participants should have received no more than 3 systemic regimens in the metastatic setting.
-
sqNSCLC (closed to enrollment): Participants with NSCLC must have predominant squamous histology. Participants must have received prior therapy with a platinum-based treatment and a checkpoint inhibitor (CPI), if eligible. Participants should have received no more than 3 lines of systemic therapy in the metastatic setting.
- Participants eligible for a tyrosine kinase inhibitor should have received such therapy. These participants should have received no more than 4 lines of systemic therapy in the metastatic setting.
-
Exocrine pancreatic adenocarcinoma (closed to enrollment): Participants with exocrine pancreatic adenocarcinoma must have predominant adenocarcinoma histology. Participants must have received prior therapy with a gemcitabine-based or 5FU-based regimen, if eligible, and should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
-
HNSCC (closed to enrollment): Participants with HNSCC in Part C must have received prior therapy with a platinum-based regimen and/or a checkpoint inhibitor (CPI), if eligible, and must have experienced disease progression following such therapy. Participants should have received no more than 3 systemic lines of therapy in the recurrent or metastatic setting.
-
-
Part E
- Participants with HNSCC must have experienced disease progression on or after their most recent systemic therapy. Participants should have received no more than 1 or 2 systemic lines of therapy in the recurrent/metastatic setting as specified below. Participants must have received a platinum-based regimen and a PD-(L)1 inhibitor.
-
Parts D, F, and G
-
Part D is closed to enrollment. Part F and Part G will enroll only participants with HNSCC.
-
Participants with HNSCC must have received no previous systemic therapy in the recurrent or metastatic disease setting.
-
Part D only
- Participants with NSCLC must have histologically or cytologically documented squamous cell NSCLC and must have received no previous systemic therapy for metastatic disease or radiation therapy to the lung that is > 30 Gy within 6 months of the first dose of study treatment.
- PD-L1 biomarker expression as determined by a PD-L1 IHC assay should be available
-
Part F only
- Participants must have CPS ≥1 by local PD-L1 IHC assay to be eligible for enrollment. Participants must be able to submit a tissue sample for retrospective PD-L1 testing. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1.
-
Part G only
- Non-EU eligibility criteria: No CPS requirement for the cohort evaluating tisotumab vedotin in combination with pembrolizumab and carboplatin.
- EU-specific eligibility criteria: Participants must have a CPS ≥1 by local PD-L1 IHC assay.
- Participants must be able to submit a tissue sample for retrospective PD-L1 testing. Tissue may be fresh biopsy or archival, collected within 2 years of Cycle 1 Day 1.
-
-
Baseline measurable disease as measured by RECIST v1. 1.
-
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
- Participants with primary neuroendocrine or sarcomatoid histologies. For HNSCC, participants may not have a primary site of nasopharynx or salivary gland.
- Active bleeding conditions
- Ocular surface disease at the time of enrollment (Note: cataract is not considered active ocular surface disease for this protocol)
- Other cancer: known past or current malignancy other than inclusion diagnosis.
- Uncontrolled tumor-related pain
- Inflammatory lung disease. Participants with pulmonary disease are allowed if systemic steroids and long-term oxygen are not required
- Peripheral neuropathy greater than or equal to Grade 2
- Active brain metastasis
- Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery).
- Part D, F, and G Only: Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A: Tisotumab Vedotin - Q3W Schedule tisotumab vedotin Tisotumab Vedotin on Day 1 of every 21-day cycle in participants with various solid tumors in 2L+ Part C: Tisotumab Vedotin - 2Q4W Schedule tisotumab vedotin Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC or sqNSCLC in 2L+ Part E: Tisotumab Vedotin - 2Q4W Schedule tisotumab vedotin Tisotumab Vedotin on Days 1 and 15 of every 28-day cycle in participants with HNSCC in the second- or third-line setting Part F: Tisotumab Vedotin Combination Therapy - Q2W Schedule tisotumab vedotin Tisotumab Vedotin + pembrolizumab. Tisotumab Vedotin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting Part G: Tisotumab Vedotin Combination Therapy - Q2W Schedule tisotumab vedotin Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule carboplatin Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC Part F: Tisotumab Vedotin Combination Therapy - Q2W Schedule pembrolizumab Tisotumab Vedotin + pembrolizumab. Tisotumab Vedotin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting Part G: Tisotumab Vedotin Combination Therapy - Q2W Schedule carboplatin Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting Part B: Tisotumab Vedotin - 3Q4W Schedule tisotumab vedotin Tisotumab Vedotin on Days 1, 8, and 15 of 28-day cycle in participants with various solid tumors in 2L+ Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule pembrolizumab Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule tisotumab vedotin Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC Part D: Tisotumab Vedotin Combination Therapy - Q3W Schedule cisplatin Tisotumab Vedotin + pembrolizumab + (carboplatin or cisplatin). Given on Day 1 of every 21-day cycle in participants with various solid tumors in 1L HNSCC or sqNSCLC Part G: Tisotumab Vedotin Combination Therapy - Q2W Schedule pembrolizumab Tisotumab Vedotin + pembrolizumab + carboplatin. Tisotumab Vedotin and carboplatin given on Days 1, 15, and 29 of every 6-week cycle. Pembrolizumab given on Day 1 of every 6-week cycle in participants with HNSCC in the first line setting
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (ORR) (Parts A, B, C, D, F, and G) Up to approximately 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
Confirmed ORR per blinded independent central review (BICR) (Part E) Up to approximately 3 years Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR
- Secondary Outcome Measures
Name Time Method Incidence of Adverse Events (AEs) Up to approximately 3 years Type, severity, and relatedness of adverse events. An AE is any untoward medical occurrence in a subject or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
Confirmed and Unconfirmed ORR Up to approximately 3 years Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by the investigator
Confirmed and Unconfirmed ORR per BICR (Part E) Up to approximately 3 years Proportion of patients who achieve a CR or PR according to RECIST v1.1 as assessed by BICR
Disease Control Rate (DCR) Up to approximately 3 years Proportion of patients who achieve a confirmed CR or PR according to 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
Duration of Response (DOR) Up to approximately 3 years Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first, as assessed by the investigator
TTR per BICR (Part E) Up to approximately 1 year Time from the start of study treatment to the first documentation of objective response, as assessed by BICR
PFS per BICR (Part E) Up to approximately 3 years Time from the start of study treatment to the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever comes first, as assessed by BICR
Overall Survival (OS) Up to approximately 4 years Time from the start of study treatment to date of death due to any cause
DOR per BICR (Part E) Up to approximately 3 years Time from the first documentation of objective response to the first documentation of PD or death due to any cause, whichever comes first, as assessed by BICR
Time to Response (TTR) Up to approximately 1 year Time from the start of study treatment to the first documentation of objective response, as assessed by investigator
Progression-free survival (PFS) Up to approximately 3 years Time from the start of study treatment to the first documentation of PD according to RECIST v1.1 or death due to any cause, whichever comes first, as assessed by the investigator
Ctrough Through 30-37 days following the last dose; up to approximately 3 years Observed plasma concentration at the end of the dosing interval
DCR per BICR (Part E) Up to approximately 3 years Proportion of patients who achieve a confirmed CR or PR according to RECIST v1.1 as assessed by BICR, or meet the stable disease (SD) criteria at least once after start of study treatment at a minimum interval of 12 weeks
Cmax Through 30-37 days following the last dose; up to approximately 3 years Maximum observed plasma concentration
Incidence of anti-therapeutic antibodies (ATAs) Through 30-37 days following the last dose; up to approximately 3 years
Trial Locations
- Locations (72)
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
UC San Diego / Moores Cancer Center
🇺🇸La Jolla, California, United States
Stanford Cancer Center / Blood and Marrow Transplant Program
🇺🇸San Jose, California, United States
Shands Cancer Center / University of Florida
🇺🇸Gainesville, Florida, United States
Mayo Clinic Florida
🇺🇸Jacksonville, Florida, United States
H. Lee Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Winship Cancer Institute / Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Northwestern Medicine Cancer Center Kishwaukee / Kishwaukee Cancer Center
🇺🇸DeKalb, Illinois, United States
Northwestern Medicine Cancer Center Delnor
🇺🇸Geneva, Illinois, United States
University of California Davis
🇺🇸Sacramento, California, United States
Poudre Valley Health System (PVHS)
🇺🇸Fort Collins, Colorado, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Northwestern Memorial Hospital
🇺🇸Chicago, Illinois, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Ingalls Cancer Care / Ingalls Memorial Hospital
🇺🇸Harvey, Illinois, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
University of Kansas Cancer Center
🇺🇸Fairway, Kansas, United States
Northwestern Medicine Cancer Center Warrenville
🇺🇸Warrenville, Illinois, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Johns Hopkins Hospital
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Karmanos Cancer Institute / Wayne State University
🇺🇸Detroit, Michigan, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
HealthPartners Institute
🇺🇸Saint Louis Park, Minnesota, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Washington University in St Louis
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Wake Forest Baptist Medical Center / Wake Forest University
🇺🇸Winston-Salem, North Carolina, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
University of Pennsylvania / Perelman Center for Advanced Medicine
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Texas Oncology - Fort Worth
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
University of Alberta / Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Hospitalier Jean Minjoz
🇫🇷Besancon, Other, France
Centre léon Bérard
🇫🇷LYON cedex 08, Other, France
APHM Hôpital Nord
🇫🇷Marseille Cedex 20, Other, France
Hopital Prive du Confluent
🇫🇷Nantes Cedex 2, Other, France
Hopital Foch
🇫🇷Suresnes, Other, France
Institut Gustave Roussy
🇫🇷Villejuif Cedex, Other, France
Ruhr-Uni. Bochum, St. Josef-Hospital
🇩🇪Bochum, Other, Germany
Universitätsklinikum Halle-Universitätsklinik und Poliklinik
🇩🇪Halle, Other, Germany
Vincentius-Diakonissen-Kliniken gAG
🇩🇪Karlsruhe, Other, Germany
Azienda Ospedaliero Universitaria (AOU) Master Domin U.O. Oncologia Medica Traslazzionale
🇮🇹Catanzaro, Other, Italy
Azienda Ospedaliera Spedali Civili di Brescia
🇮🇹Brescia, Other, Italy
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori- IRST S.r.l
🇮🇹Meldola FC, Other, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Other, Italy
Seconda Università degli Studi di Napoli, AOU
🇮🇹Napoli, Other, Italy
Oncologia Medica, Ospedale Civile S. Maria delle Croci
🇮🇹Ravenna, Other, Italy
PU Campus Bio-medico di Roma
🇮🇹Roma, Other, Italy
Azienda USL Toscana Centro
🇮🇹Pistoia, Other, Italy
Pan American Center for Oncology Trials, LLC
🇵🇷Rio Piedras, Puerto Rico
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Other, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸Badalona, Other, Spain
Hospital Quironsalud Barcelona Instituto Oncologico Baselga
🇪🇸Barcelona, Other, Spain
Hospital Clinico San Carlos
🇪🇸Madrid, Other, Spain
HM Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Other, Spain
Althaia Xarxa Assistencial Manresa
🇪🇸Manresa, Other, Spain
Son LLatzer University Hospital
🇪🇸Palma de Mallorca, Other, Spain
Guys and St Thomas Hospital
🇬🇧London, Other, United Kingdom
The Royal Marsden Hospital Chelsea
🇬🇧London, Other, United Kingdom
The Royal Marsden NHS Foundation Trust (RM)
🇬🇧London, Other, United Kingdom