IDE196 (Darovasertib) in Combination with Crizotinib As First-line Therapy in Metastatic Uveal Melanoma
- Conditions
- Metastatic Uveal Melanoma
- Interventions
- Registration Number
- NCT05987332
- Lead Sponsor
- IDEAYA Biosciences
- Brief Summary
This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A\*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).
- Detailed Description
This study is designed as a multi-stage Phase 2 study within a Phase 3 study to evaluate the safety, tolerability, pharmacokinetics, dose-exposure relationship, and anti-tumor activity of IDE196 in combination with crizotinib compared to the comparator arm of investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).
The Phase 2a dose optimization stage will evaluate two doses of IDE196 in combination with crizotinib compared to the comparator arm. Participants will be randomized to the three treatment arms. At the point of optimal IDE196 + crizotinib dose selection, the other dose arm will be dropped with discontinuation of enrollment to that arm. Participants receiving the IDE196 dose (in combination with crizotinib) that is not selected, will be offered the choice to remain on the same dose or change to the chosen optimal dose.
The optimal dose will be chosen to complete the Phase 2b portion. The Phase 2b part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms.
The Phase 3 part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 420
- Histological or cytological confirmed Metastatic Uveal Melanoma
- HLA-A*02:01 negative
- No prior systemic therapy in the metastatic or advanced setting or regional or liver-directed therapy. Ablations or surgical resection of oligometastatic disease, and neoadjuvant or adjuvant therapy is allowed
- Measurable disease per RECIST 1.1
- Able to be safely administered and absorb study therapy
- ECOG performance status 0 or 1
- Life expectancy of ≥3 months
- Adequate organ function
- Previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11
- Concurrent malignant disease
- AEs from prior anti-cancer therapy that have not resolved to Grade ≤1
- Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require corticosteroids
- High risk of syncope
- Known AIDS related illness or active Hep B/C
- Active adrenal insufficiency, active colitis, or active inflammatory bowel disease
- History of interstitial lung disease, active pneumonitis, or history of pneumonitis
- Active infection requiring systemic antibiotic therapy
- Use of hematopoietic colony-stimulating factors (CSF) prior to start of study drug
- Females who are pregnant or breastfeeding
- History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies
- Contraindication for treatment with investigator's choice therapies as per applicable labelling
- History of stroke within the last 6 months of the first dose of study drug
- Has any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the participant inappropriate for entry into the study, including institutionalization on the basis of an official or court order
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 2a / 2b / 3 Comparator Arm Nivolumab Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine. Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib IDE196 Chosen combination dose of IDE196 + crizotinib will be tested in additional participants. Phase 2a / 2b / 3 Comparator Arm Pembrolizumab Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine. Phase 2a Dose Optimization of IDE196 + crizotinib Crizotinib Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose. Phase 2a / 2b / 3 Comparator Arm Dacarbazine Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine. Phase 2a Dose Optimization of IDE196 + crizotinib IDE196 Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose. Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib Crizotinib Chosen combination dose of IDE196 + crizotinib will be tested in additional participants. Phase 2a / 2b / 3 Comparator Arm Ipilimumab Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
- Primary Outcome Measures
Name Time Method Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment Approximately 2 years PFS per RECIST 1.1
Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment Approximately 4 years OS from randomization to date of death due to any cause
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment Approximately 2 years PFS per RECIST 1.1
Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment Approximately 2 years DOR per RECIST 1.1
Phase 2a: Dose exposure response of IDE196 Approximately 5 months Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma
Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment Approximately 2 years ORR per RECIST 1.1
Safety of IDE196 + Crizotinib: Incidence of Adverse Events Approximately 2 years Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs as measured by CTCAE V5.0
Phase 2a: Dose exposure response of Crizotinib Approximately 5 months Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma
Change from baseline over time and between treatment arms in EORTC QLQ-C30 Approximately 2 years Global health status and quality of life will be assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.
Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores Approximately 2 years General health status will be assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.
Trial Locations
- Locations (132)
Honor Health
🇺🇸Scottsdale, Arizona, United States
Moores Cancer Center
🇺🇸La Jolla, California, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
LUMC (Leids Universitair Medisch Centrum)
🇳🇱Leiden, Netherlands
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
🇵🇱Warsaw, Poland
Catalan Institute of Oncology
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Hospital General Universitario Valencia
🇪🇸Valencia, Spain
Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung
🇨🇭Zuerich, Switzerland
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Mount Vernon Cancer Centre East & North Herts NHS Trust
🇬🇧Northwood, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
California Pacific Medical Center (CPMC)
🇺🇸San Francisco, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
SCRI at HealthONE
🇺🇸Denver, Colorado, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Northside Hospital Atlanta
🇺🇸Atlanta, Georgia, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
The Cancer and Hematology Centers
🇺🇸Grand Rapids, Michigan, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Burnsville, Minnesota, United States
Northwell Health
🇺🇸Manhasset, New York, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Health System
🇺🇸Durham, North Carolina, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology- DFW
🇺🇸Dallas, Texas, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Princess Alexander Hospital
🇦🇺Brisbane, Queensland, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Centre Hospitalier de l'Universite de Montreal- CHUM
🇨🇦Montréal, Quebec, Canada
Sir Charles Gairdner Hospital
🇦🇺Perth, Washington, Australia
Queen Elizabeth Hospital
🇦🇺Adelaide, Australia
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Cross Cancer Institute, University of Alberta
🇨🇦Edmonton, Alberta, Canada
NCT Heidelberg
🇩🇪Heidelberg, Baden- Württemberg, Germany
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
The Leon Berard Center
🇫🇷Lyon, France
Institut Curie
🇫🇷Paris, France
Universitätsklinikum Essen (AöR)
🇩🇪Essen, North Rhine-Westphalia, Germany
Universitätsklinikum Köln
🇩🇪Köln, North Rhine-Westphalia, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Saxony, Germany
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat-Gan, Israel
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Nazionale dei Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Fondazione Policlinico Gemelli IRCCS
🇮🇹Roma, Italy
AOUS Policlinico Le Scotte
🇮🇹Siena, Italy
Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku
🇵🇱Gdańsk, Poland
Honor Health
🇺🇸Scottsdale, Arizona, United States
Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Northside Hospital Atlanta
🇺🇸Atlanta, Georgia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
The Cancer and Hematology Centers
🇺🇸Grand Rapids, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
UCLA Medical Center
🇺🇸Los Angeles, California, United States
The Angeles Clinic and Research Institute
🇺🇸Los Angeles, California, United States
California Pacific Medical Center (CPMC)
🇺🇸San Francisco, California, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
SCRI at HealthONE
🇺🇸Denver, Colorado, United States
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
University of Iowa
🇺🇸Iowa City, Iowa, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Burnsville, Minnesota, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northwell Health
🇺🇸Manhasset, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
Westmead Hospital
🇦🇺Sydney, New South Wales, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Washington, Australia
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburg, Pennsylvania, United States
Princess Alexander Hospital
🇦🇺Brisbane, Queensland, Australia
Queen Elizabeth Hospital
🇦🇺Adelaide, Australia
Centre Hospitalier de l'Universite de Montreal- CHUM
🇨🇦Montréal, Quebec, Canada
Universitätsklinikum Essen (AöR)
🇩🇪Essen, North Rhine-Westphalia, Germany
Universitätsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Saxony, Germany
Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku
🇵🇱Gdańsk, Poland
Catalan Institute of Oncology
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Duke University Health System
🇺🇸Durham, North Carolina, United States
The Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Houston Methodist Cancer Center
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
Texas Oncology- DFW
🇺🇸Dallas, Texas, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Belgium
Institut Curie
🇫🇷Paris, France
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
The Leon Berard Center
🇫🇷Lyon, France
Charité - Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Fondazione Policlinico Gemelli IRCCS
🇮🇹Roma, Italy
Cross Cancer Institute, University of Alberta
🇨🇦Edmonton, Alberta, Canada
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Sheba Medical Center
🇮🇱Ramat-Gan, Israel
AOUS Policlinico Le Scotte
🇮🇹Siena, Italy
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
NCT Heidelberg
🇩🇪Heidelberg, Baden- Württemberg, Germany
Universitätsklinikum Köln
🇩🇪Köln, North Rhine-Westphalia, Germany
LUMC (Leids Universitair Medisch Centrum)
🇳🇱Leiden, Netherlands
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy
🇵🇱Warsaw, Poland
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Istituto Nazionale dei Tumori Fondazione Pascale
🇮🇹Napoli, Italy
Hospital Clínico Universitario de Santiago de Compostela
🇪🇸Santiago de Compostela, Spain
Hospital General Universitario Valencia
🇪🇸Valencia, Spain
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom
Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung
🇨🇭Zuerich, Switzerland
Mount Vernon Cancer Centre East & North Herts NHS Trust
🇬🇧Northwood, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust
🇬🇧Wirral, United Kingdom