IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma

NCT ID: NCT05987332

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-10-31

Study Completion Date

2028-01-15

Brief Summary

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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

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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.

Conditions

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Metastatic Uveal Melanoma

Keywords

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IDE196 Darovasertib Protein Kinase C Metastatic Uveal Melanoma Melanoma Ocular Oncology Ophthalmology Crizotinib Ocular melanoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 2a Dose Optimization of IDE196 + crizotinib

Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.

Group Type EXPERIMENTAL

IDE196

Intervention Type DRUG

Dosed orally, twice daily

Crizotinib

Intervention Type DRUG

Dosed orally, twice daily

Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib

Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.

Group Type EXPERIMENTAL

IDE196

Intervention Type DRUG

Dosed orally, twice daily

Crizotinib

Intervention Type DRUG

Dosed orally, twice daily

Phase 2a / 2b / 3 Comparator Arm

Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type DRUG

IV administration every 3 weeks

Ipilimumab

Intervention Type DRUG

IV administration every 3 weeks for 4 Cycles

Nivolumab

Intervention Type DRUG

IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance

Dacarbazine

Intervention Type DRUG

IV administration every 3 Weeks

Interventions

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IDE196

Dosed orally, twice daily

Intervention Type DRUG

Crizotinib

Dosed orally, twice daily

Intervention Type DRUG

Pembrolizumab

IV administration every 3 weeks

Intervention Type DRUG

Ipilimumab

IV administration every 3 weeks for 4 Cycles

Intervention Type DRUG

Nivolumab

IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance

Intervention Type DRUG

Dacarbazine

IV administration every 3 Weeks

Intervention Type DRUG

Other Intervention Names

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Darovasertib XALKORI Keytruda Yervoy Opdivo DTIC-Dome

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IDEAYA Biosciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hetal Patel, MD, MSHS, CHCQM

Role: STUDY_DIRECTOR

IDEAYA Biosciences

Locations

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Honor Health

Scottsdale, Arizona, United States

Site Status RECRUITING

Moores Cancer Center

La Jolla, California, United States

Site Status RECRUITING

UCLA Medical Center

Los Angeles, California, United States

Site Status RECRUITING

The Angeles Clinic and Research Institute

Los Angeles, California, United States

Site Status RECRUITING

California Pacific Medical Center (CPMC)

San Francisco, California, United States

Site Status RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status RECRUITING

SCRI at HealthONE

Denver, Colorado, United States

Site Status RECRUITING

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Northside Hospital Atlanta

Atlanta, Georgia, United States

Site Status RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

The Cancer and Hematology Centers

Grand Rapids, Michigan, United States

Site Status RECRUITING

Minnesota Oncology Hematology, P.A.

Burnsville, Minnesota, United States

Site Status RECRUITING

Mayo Clinic

Rochester, Minnesota, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Northwell Health

Manhasset, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke University Health System

Durham, North Carolina, United States

Site Status RECRUITING

University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

Texas Oncology- DFW

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status RECRUITING

Houston Methodist Cancer Center

Houston, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Westmead Hospital

Sydney, New South Wales, Australia

Site Status RECRUITING

Princess Alexander Hospital

Brisbane, Queensland, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Alfred Health

Melbourne, Victoria, Australia

Site Status RECRUITING

Sir Charles Gairdner Hospital

Perth, Washington, Australia

Site Status RECRUITING

Queen Elizabeth Hospital

Adelaide, , Australia

Site Status RECRUITING

Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status ACTIVE_NOT_RECRUITING

Algemene Medische Oncologie UZ

Leuven, , Belgium

Site Status ACTIVE_NOT_RECRUITING

Cross Cancer Institute, University of Alberta

Edmonton, Alberta, Canada

Site Status RECRUITING

BC Cancer Agency

Vancouver, British Columbia, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Centre Hospitalier de l'Universite de Montreal- CHUM

Montreal, Quebec, Canada

Site Status RECRUITING

The Leon Berard Center

Lyon, , France

Site Status ACTIVE_NOT_RECRUITING

Institut Curie

Paris, , France

Site Status ACTIVE_NOT_RECRUITING

NCT Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Köln

Cologne, North Rhine-Westphalia, Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Essen (AöR)

Essen, North Rhine-Westphalia, Germany

Site Status ACTIVE_NOT_RECRUITING

Universitätsklinikum Carl Gustav Carus Dresden

Dresden, Saxony, Germany

Site Status ACTIVE_NOT_RECRUITING

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status ACTIVE_NOT_RECRUITING

Hadassah Medical Center

Jerusalem, , Israel

Site Status RECRUITING

Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status ACTIVE_NOT_RECRUITING

Istituto Nazionale dei Tumori Fondazione Pascale

Napoli, , Italy

Site Status ACTIVE_NOT_RECRUITING

Fondazione Policlinico Gemelli IRCCS

Roma, , Italy

Site Status ACTIVE_NOT_RECRUITING

AOUS Policlinico Le Scotte

Siena, , Italy

Site Status ACTIVE_NOT_RECRUITING

LUMC (Leids Universitair Medisch Centrum)

Leiden, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku

Gdansk, , Poland

Site Status ACTIVE_NOT_RECRUITING

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy

Warsaw, , Poland

Site Status ACTIVE_NOT_RECRUITING

Catalan Institute of Oncology

L'Hospitalet de Llobregat, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Universitario La Paz

Madrid, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Clínico Universitario de Santiago de Compostela

Santiago de Compostela, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status ACTIVE_NOT_RECRUITING

Hospital General Universitario Valencia

Valencia, , Spain

Site Status ACTIVE_NOT_RECRUITING

Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung

Zurich, , Switzerland

Site Status RECRUITING

The Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status RECRUITING

The Clatterbridge Cancer Centre NHS Foundation Trust

Metropolitan Borough of Wirral, , United Kingdom

Site Status RECRUITING

Mount Vernon Cancer Centre East & North Herts NHS Trust

Northwood, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Canada France Germany Israel Italy Netherlands Poland Spain Switzerland United Kingdom

Central Contacts

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IDEAYA Clinical Trials

Role: CONTACT

Phone: 1-855-433-2246

Email: [email protected]

Facility Contacts

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Oncology Clinical Trials Nurse Navigator

Role: primary

Role: backup

Katie O'Neil, BA

Role: primary

Jazelle Molina

Role: backup

Adyel Annelus

Role: primary

Elizabeth Seja

Role: backup

Saba Mukarram

Role: primary

Denise Fortun

Role: primary

CPMC Clinical Research Group

Role: backup

Sonia Contreras Martinez, BSN

Role: primary

Sarah Mayer, BA

Role: primary

Victoria Mayer, VA

Role: backup

SCRI Front Desk

Role: primary

Role: primary

Nikhil Khushalani, MD

Role: primary

Leticia Tetteh, BSN

Role: backup

Central Research Department

Role: primary

Mohammed Milhelm, MBBS

Role: primary

Kamaneh Montazeri, MD

Role: primary

Ryan Sullivan, MD

Role: backup

Rizwan Haq

Role: primary

Linnea Drew

Role: backup

The Cancer and Hematology Centers

Role: primary

Jessica Miller, RN

Role: backup

Kayla McDonald

Role: primary

Referral Office

Role: primary

Amer Alyasiry, MHS

Role: primary

Tyler Klein

Role: backup

Benjamin Switzer, DO

Role: primary

igor Puzanov, MD

Role: backup

Shaheer Khan, MD

Role: primary

Tracy Green, BS

Role: backup

Alexander Shoushtari, MD

Role: primary

James Smithy, MD

Role: backup

Carol Ann Wiggs, BSN

Role: primary

Emily Bolch

Role: backup

Role: primary

Lucy Kennedy, MD

Role: primary

Marlana Orloff

Role: primary

Kristie Hensel

Role: backup

Amy Rose, RN,BSN

Role: primary

Jennifer Cleric, ND, RN

Role: backup

SCRI Oncology Partners

Role: primary

Christine Terraciano

Role: primary

Sanjay Chandrasekaran, MD

Role: primary

Desiree Pierre, BS

Role: backup

Anaum Maqsood

Role: primary

Alexandra Ikeguchi

Role: primary

Matteo Carlino, MD

Role: primary

Janine Thomas

Role: primary

Damien Kee, MD

Role: primary

Joanne Tonkin

Role: primary

Rose McDowell

Role: backup

Roberts-Thomson, MD

Role: primary

John Walker, MD,PhD,FRCPC

Role: primary

Alison Weppler, MD FRCPC, MPH

Role: primary

Melissa Dalva

Role: primary

Rahima Jamal, MD

Role: primary

Chantal Gosselin

Role: backup

Jonathan Cohen, MD

Role: primary

Annaelle Dynovisz, SC

Role: backup

Ronnie Shapira, MD

Role: primary

Egle Ramelyte, Dr. med Dr. sc.med.

Role: primary

Ruth Orr

Role: primary

Joseph Sacco, Professor

Role: primary

Paul Nathan, Prof. Dr. med.

Role: primary

Other Identifiers

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IDE196-002

Identifier Type: -

Identifier Source: org_study_id