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Metastatic Uveal MelanomaPhase 2/3NCT05987332

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

A Phase 2/3 study testing IDE196, Crizotinib and Pembrolizumab in people with Metastatic Uveal Melanoma, run by IDEAYA Biosciences at 68 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Uveal Melanoma
What is being tested?
IDE196, Crizotinib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
420 participants
Where
68 sitesin 13 countries
Study dates
31 Oct 2023to 15 Jan 2028
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological or cytological confirmed Metastatic Uveal Melanoma
  • HLA-A*02:01 negative
  • No prior systemic therapy in the metastatic or advanced setting 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

Who cannot join

  • 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 or falls
  • Known AIDS related illness
Show all 16Show fewer
  • Active adrenal insufficiency, active colitis, or active inflammatory bowel disease
  • History of interstitial lung disease, active pneumonitis, or history of pneumonitis requiring steroids
  • Active infection requiring systemic antibiotic therapy or active Hepatitis B/C
  • Major surgery, radiotherapy, or use of hematopoietic colony-stimulating factors (CSF) within 2 weeks 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
  • Impaired Cardiac function or clinically significant cardiac diseases, including angina pectoris or acute myocardial infarction <= 6 months prior to start of study treatment
  • 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

Trial locations and contacts

68 sites in 13 countries.

68 sites in 13 countries

United States31 sites

  • Northside Hospital Atlanta

    Atlanta, Georgia, 30342

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Minnesota Oncology Hematology, P.A.

    Burnsville, Minnesota, 55337

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Texas Oncology- DFW

    Dallas, Texas, 75246

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • SCRI at HealthONE

    Denver, Colorado, 80218

  • Duke University Health System

    Durham, North Carolina, 27710

  • The Cancer and Hematology Centers

    Grand Rapids, Michigan, 49546

  • Houston Methodist Cancer Center

    Houston, Texas, 77030

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of Iowa

    Iowa City, Iowa, 52242

  • Moores Cancer Center

    La Jolla, California, 92093

  • UCLA Medical Center

    Los Angeles, California, 90024

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Northwell Health

    Manhasset, New York, 11030

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • SCRI Oncology Partners

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • California Pacific Medical Center (CPMC)

    San Francisco, California, 94115

  • University of California San Francisco

    San Francisco, California, 94143

  • Honor Health

    Scottsdale, Arizona, 85258

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Australia6 sites

  • Queen Elizabeth Hospital

    Adelaide

  • Princess Alexander Hospital

    Brisbane, Queensland, 4102

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, 3000

  • Alfred Health

    Melbourne, Victoria, 3168

  • Sir Charles Gairdner Hospital

    Perth, Washington, 6009

  • Westmead Hospital

    Sydney, New South Wales, 2145

Other trials in Australia

Germany5 sites

  • Charité - Universitätsmedizin Berlin

    Berlin, 12203

  • Universitätsklinikum Köln

    Cologne, North Rhine-Westphalia, 50937

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden, Saxony, 1307

  • Universitätsklinikum Essen (AöR)

    Essen, North Rhine-Westphalia, 45147

  • NCT Heidelberg

    Heidelberg, Baden-Wurttemberg, 69120

Other trials in Germany

Spain5 sites

  • Catalan Institute of Oncology

    L'Hospitalet de Llobregat, 8908

  • Hospital Universitario La Paz

    Madrid, 28046

  • Hospital Clínico Universitario de Santiago de Compostela

    Santiago de Compostela, 15706

  • Hospital Universitario Virgen Macarena

    Seville, 41009

  • Hospital General Universitario Valencia

    Valencia, 46014

Other trials in Spain

Canada4 sites

  • Cross Cancer Institute, University of Alberta

    Edmonton, Alberta, T6G 1Z2

  • Centre Hospitalier de l'Universite de Montreal- CHUM

    Montreal, Quebec, H2X 0C1

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

  • BC Cancer Agency

    Vancouver, British Columbia, V5Z4C2

Other trials in Canada

Italy4 sites

  • Fondazione IRCCS Istituto Nazionale dei Tumori

    Milan, 20133

  • Istituto Nazionale dei Tumori Fondazione Pascale

    Naples, 80131

  • Fondazione Policlinico Gemelli IRCCS

    Roma, 00168

  • AOUS Policlinico Le Scotte

    Siena, 53100

Other trials in Italy

United Kingdom3 sites

  • The Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • The Clatterbridge Cancer Centre NHS Foundation Trust

    Metropolitan Borough of Wirral, CH63 4JY

  • Mount Vernon Cancer Centre East & North Herts NHS Trust

    Northwood, HA6 2RN

Other trials in United Kingdom

Belgium2 sites

  • Cliniques Universitaires Saint Luc

    Brussels, 1200

  • Algemene Medische Oncologie UZ

    Leuven, 3000

Other trials in Belgium

France2 sites

  • The Leon Berard Center

    Lyon

  • Institut Curie

    Paris, 75005

Other trials in France

Israel2 sites

  • Hadassah Medical Center

    Jerusalem, 91120

  • Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

Poland2 sites

  • Ośrodek Badań Klinicznych Wczesnych Faz, Uniwersyteckie Centrum Kliniczne w Gdańsku

    Gdansk, 80-214

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

    Warsaw, 02-781

Other trials in Poland

Netherlands1 site

  • LUMC (Leids Universitair Medisch Centrum)

    Leiden, 2333 ZA

Other trials in Netherlands

Switzerland1 site

  • Dermatologische Klinik, USZ Flughafen Geschoss 7 - Klinische Forschung

    Zurich, 8058

Other trials in Switzerland

About this study

Official title: IDE196 (Darovasertib) in Combination With Crizotinib Versus Investigator's Choice of Treatment as First-line Therapy in HLA-A2 Negative Metastatic Uveal Melanoma (DAR-UM-2)

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).

Read the 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 to evaluate the primary endpoint of overall survival (OS).

Being tested
IDE196, Crizotinib, Pembrolizumab, Ipilimumab, Nivolumab
Keywords
IDE196, Darovasertib, Protein Kinase C, Metastatic Uveal Melanoma, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma
Medical subject headings
Uveal Melanoma, Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IDE196Drug

    Also called Darovasertib

    Dosed orally, twice daily

  • CrizotinibDrug

    Also called XALKORI

    Dosed orally, twice daily

  • PembrolizumabDrug

    Also called Keytruda

    IV administration every 3 weeks

  • IpilimumabDrug

    Also called Yervoy

    IV administration every 3 weeks for 4 Cycles

  • NivolumabDrug

    Also called Opdivo

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

  • DacarbazineDrug

    Also called DTIC-Dome

    IV administration every 3 Weeks

Study groups in NCT05987332
Study groupRoleWhat they receive
Phase 2a Dose Optimization of IDE196 + crizotinibExperimentalMultiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.
Receives: Drug: IDE196; Drug: Crizotinib
Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinibExperimentalChosen combination dose of IDE196 + crizotinib will be tested in additional participants.
Receives: Drug: IDE196; Drug: Crizotinib
Phase 2a / 2b / 3 Comparator ArmActive comparatorParticipants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
Receives: Drug: Pembrolizumab; Drug: Ipilimumab; Drug: Nivolumab; Drug: Dacarbazine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 2a: To determine the optimal dose of IDE196 + Crizotinib combination for Phase 2B and Phase 3 by evaluating the following:

    dose exposure response (safety and efficacy) relationship, plasma concentration profiles and pharmacokinetic (PK) parameters, treatment-emergent Adverse Events (TEAEs), laboratory abnormalities, electrocardiogram (ECG), and vital sign changes and study treatment discontinuation due to AEs.

    Measured: Approximately 5 months

  2. Phase 2 Progression-Free Survival (PFS)

    by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment per RECIST v1.1

    Measured: Approximately 2 years

  3. Phase 3 Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment.

    OS from randomization to date of death due to any cause

    Measured: Approximately 4 years

Secondary outcomes (11)

  1. Safety of IDE196 + Crizotinib: Incidence of Adverse Events

    Treatment emergent adverse events will be summarized by all AEs, including by Grade ≥3, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs as measured by CTCAE v5.0.

    Measured: Approximately 2 years

  2. Phase 2a: Dose-exposure-response of IDE196 as measured by correlating the concentration of IDE196 in plasma with safety and efficacy.

    Dose exposure response of IDE196.

    Measured: Approximately 5 months

  3. Phase 2a: Dose-exposure-response of Crizotinib measured by correlating the concentration of Crizotinib in plasma with safety and efficacy.

    Dose exposure response of Crizotinib

    Measured: Approximately 5 months

  4. Phase 2b + 3: Progression-Free Survival (PFS) per Investigator Assessment of IDE196 + Crizotinib compared to investigator's choice of treatment .

    PFS per RECIST v1.1

    Measured: Approximately 2 years

  5. Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment

    ORR per RECIST v1.1

    Measured: Approximately 2 years

  6. Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment

    DOR per RECIST v1.1

    Measured: Approximately 2 years

  7. Change from baseline over time and between treatment arms in 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 in EORTC QLQ-C30 scores

    Measured: Approximately 2 years

  8. Change from baseline over time and between treatment arms in

    EuroQoL (EQ)-5D-5L scores

    Measured: Approximately 2 years

  9. Best Objective Response (BOR) per BICR and Investigator Assessment of IDE196 + Crizotinib compared to Investigator's choice of treatment

    Best Objective Response (BOR) per RECIST v1.1

    Measured: Approximately 2 years

  10. Disease Control Rate (DCR) per BICR and Investigator Assessment of IDE196 + Crizotinib compared to investigator's choice of treatment.

    Disease Control Rate (DCR) per RECIST v1.1

    Measured: Approximately 2 years

  11. Time to response as assessed by Investigator and BICR

    Time to response per RECIST v1.1

    Measured: Approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start31 Oct 2023
  3. Primary completion15 Jan 2027 (estimated)
  4. Study completion15 Jan 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
420 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05987332
Sponsor's protocol ID
IDE196-002
Status last verified
Feb 2026
First submitted
12 Jul 2023
Last updated
17 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing IDE196, Crizotinib and Pembrolizumab in people with Metastatic Uveal Melanoma, run by IDEAYA Biosciences at 68 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in United States, Australia, Germany, Spain, Canada and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 2a: To determine the optimal dose of IDE196 + Crizotinib combination for Phase 2B and Phase 3 by evaluating the following: (time frame: Approximately 5 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05987332.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2026.

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