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Metastatic Uveal MelanomaPhase 1/2NCT03947385

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

A Phase 1/2 study testing IDE196, Binimetinib and Crizotinib in people with Metastatic Uveal Melanoma and Cutaneous Melanoma, run by IDEAYA Biosciences at 15 sites in 3 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IDE196, Binimetinib and Crizotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
336 participants
Where
15 sitesin 3 countries
Study dates
28 Jun 2019to 15 Jun 2027
Phase
Phase 1/2
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

  • Patient must be ≥18 years of age and able to provide written informed consent
  • Diagnosis of the following:
  • o MUM: Uveal melanoma with histological or cytological confirmed metastatic disease. Metastatic disease may be treatment naïve or have progressed on or after most recent therapy. If the most recent therapy was an immune-oncology agent, PD must be confirmed.
  • If a patient is treatment naïve and human leukocyte antigen (HLA)-A*02:01 positive***, documentation is required to provide rationale why treatment with tebentafusp is not the ideal firstline treatment approach or of the patient's intolerance to tebentafusp.
  • To be enrolled in the HLA-A02:01 positive cohort, HLA status must be documented by test results from a CAP/CLIA-certified laboratory.
  • Measurable disease per RECIST v1.1
Show all 13Show fewer
  • Eastern Cooperative Oncology Group ≤1 and expected life expectancy of > 3 months
  • Adequate organ function at screening
  • Adequate contraceptive measures for non-sterilized male and female patients of childbearing potential
  • Crizotinib Combination Additional Inclusion Criteria:
  • Prior chemotherapy other therapies as applicable or major surgeries must have been completed at least 4 weeks prior to initiation of crizotinib
  • Patients with preexisting peripheral neuropathy can be included if it is Grade 1 or lower, prior to initiation of crizotinib Biopsy-eligible patients
  • Accessible lesion(s) that permit a total of at least two biopsies without unacceptable risk of a significant procedural complication.

Who cannot join

  • Previous treatment with a PKC inhibitor
  • Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors
  • Known symptomatic brain metastases
  • Adverse events from prior anti-cancer therapy that have not resolved
  • Known acquired immunodeficiency syndrome (AIDS)-related illness, hepatitis B virus, or hepatitis C virus
  • Active infection requiring ongoing therapy
Show all 29Show fewer
  • Recent surgery or radiotherapy
  • Prior gastrectomy or upper bowel removal or any other gastrointestinal disorder or defect
  • Females who are pregnant or breastfeeding
  • Impaired cardiac function
  • Treatment with prohibited medications that cannot be discontinued prior to study entry
  • For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib, allergy to mammalian meat products and gelatin
  • Crizotinib Combination Additional Exclusion Criteria:
  • Prior therapy directly targeting ALK, MET, or ROS1
  • Spinal cord compression
  • History of pneumonitis or interstitial lung disease
  • History of syncope
  • History of thromboembolic or cerebrovascular events ≤12 weeks prior to first dose of study treatment
  • PK Substudy (optional) with Pravastatin Additional Exclusion Criteria:
  • Taken any dose of statin or inhibitor of organic anion transporting polypeptide within 7 days prior to enrollment in the study and cannot refrain from them through C2D1
  • Taken drugs that interfere with the absorption, metabolism, or elimination of pravastatin
  • Any contraindication associated to the use of statins or hypersensitivity component of pravastatin
  • Active liver disease
  • DDI Cocktail Substudy Additional Exclusion Criteria:
  • Treatment with bupropion, repaglinide, flurbiprofen, omeprazole, esomeprazole, midazolam, and dabigatran etexilate within 7 days prior to Cycle 1 Day -1.
  • Intake of vitamin supplements containing Vitamin B6 (pyridoxine), grapefruit/grapefruit juice, or Seville orange juice within 7 days prior to Cycle 1 Day -1.
  • Intake of any strong or moderate inhibitor of CYP2B6, CYP2CI, CYP2C9, CYP2C10 and OAT3 is prohibited within 7 days or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
  • Moderate and strong inhibitors of CYP2A4/5 or P-gp are prohibited within 7 days, or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
  • Intake of strong or moderate inducers of CYP3A4/5, CYP2B6, CYP2C9, CYP2C19, or OAT3 is prohibited during 15 days, or 5 half-lives, whichever is longer, prior to Cycle 1 Day -1.

Trial locations and contacts

15 sites in 3 countries. Contact the study team or a site near you to ask about taking part.

IDEAYA Clinical Trials contact

855-IDEA-BIO (855-433-2246)

IDEAYAClinicalTrials@ideayabio.com

15 sites in 3 countries

United States12 sites, 7 recruiting

  • University of Cincinnati Cancer Center

    Cincinnati, Ohio, 45267

    513-584-7698

    Trisha Wise-Draper, MD

    Recruiting

  • The Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

    Active, not recruiting

  • SCRI - Denver

    Denver, Colorado, 80218

    Ryan Weight, MD, ryan.weight@theskincancerinstitute.com

    Ryan Weight, MD

    Recruiting

  • Duke University Medical Center

    Durham, North Carolina, 27710

    Carol A Wiggs, cao13@duke.edu

    April Salama, MD

    Recruiting

  • Cancer Hematology Centers Western Michigan

    Grand Rapids, Michigan, 49503

    Active, not recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Jordi Ahnert, MD, JRodon@mdanderson.org

    Jordi Rodon Ahnert, MD

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Active, not recruiting

  • UCLA Medical Center

    Los Angeles, California, 90095

    Bartosz Chmielowski, MD, BChmielowski@mednet.ucla.edu

    Bartosz Chmielowski, MD

    Recruiting

  • The Sarah Cannon Research Institute/Tennessee Oncology

    Nashville, Tennessee, 37203

    askSARAH, 844-482-4812

    Meredith McKean, MD

    Recruiting

  • Columbia University Medical Center - Herbert Irving Pavilion

    New York, New York, 10032

    Active, not recruiting

  • Sidney Kimmel Cancer Center at Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

    Marlana Orloff, MD, marlana.orloff@jefferson.edu

    Marlana Orloff, MD

    Recruiting

  • San Francisco Oncology Associates

    San Francisco, California, 94115

    Active, not recruiting

Other trials in United States

Australia2 sites

  • Westmead Hospital

    Sydney, New South Wales

    Active, not recruiting

  • Queensland

    Woolloongabba, 4102

    Active, not recruiting

Other trials in Australia

Canada1 site

  • Princess Margaret Cancer Centre

    Toronto, Ontario, OPG 7-815

    Active, not recruiting

Other trials in Canada

About this study

Official title: A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.

Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Read more

Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.

Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.

As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.

Being tested
IDE196, Binimetinib, Crizotinib
Keywords
Metastatic Uveal Melanoma, Uveal Melanoma, Protein Kinase C, Ophthalmology, Ocular Oncology, Darovasertib, IDE196, Ocular Melanoma
Medical subject headings
Uveal Melanoma, Melanoma, Colorectal Neoplasms

What participants receive

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

  • IDE196Drug

    Also called Protein Kinase C (PKC) Inhibitor

    IDE196 dosed orally, twice daily for each 28-day cycle

  • BinimetinibDrug

    Also called MEKTOVI

    Binimetinib dosed orally, twice daily for each 28-day cycle

  • CrizotinibDrug

    Also called XALKORI

    Crizotinib dosed orally, twice daily for each 28-day cycle

Study groups in NCT03947385
Study groupRoleWhat they receive
Dose Escalation Monotherapy (Enrollment Complete)ExperimentalIDE196 dosed orally, twice daily (BID) for each 28-day cycle
Receives: Drug: IDE196
Dose Expansion Monotherapy (Enrollment Complete)ExperimentalRP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
Receives: Drug: IDE196
Dose Escalation Binimetinib Combination (Enrollment Complete)ExperimentalIDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle
Receives: Drug: IDE196; Drug: Binimetinib
Dose Expansion Binimetinib Combination (Enrollment Complete)ExperimentalRP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
Receives: Drug: IDE196; Drug: Binimetinib
Dose Escalation Crizotinib Combination (Enrollment Complete)ExperimentalIDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Receives: Drug: IDE196; Drug: Crizotinib
Dose Expansion Crizotinib Combination (Enrolling)ExperimentalMUM patients (previously treated or treatment naive) with human leukocyte antigen (HLA)-A*02:01 positive status. Includes a nested PK sub-study with Pravastatin (~22 participants) to evaluate the impact of pravastatin PK profiles after continuous dosing of IDE196. Includes a nested PK Cocktail DDI sub-study (~15 participants) to evaluate the impact on the PK of bupripion, repaglinide, flurbiprofen, omeprazole, midazolam, dabigatran etexilate, and the exposures of the OAT3 biomarker PDA by IDE196 in combination with crizotinib.
Receives: Drug: IDE196; Drug: Crizotinib
Dose Optimization Crizotinib Combination (Enrollment Complete)ExperimentalIDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
Receives: Drug: IDE196; Drug: Crizotinib
Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete)ExperimentalCrizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle
Receives: Drug: IDE196; Drug: Crizotinib

What is being measured

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

  1. Dose-limiting Toxicity (DLT)

    Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Measured: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  2. Incidence of Adverse Events

    Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Measured: Approx. 8 months

  3. Maximum Tolerated Dose (MTD)

    Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Measured: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

  4. Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Measured: Approx. 6 months

  5. Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

    Measured: Approx. 6 months

  6. Plasma Concentrations of Crizotinib administered in combination with IDE196

    Pharmacokinetics of Crizotinib in combination with IDE196

    Measured: Approx. 6 months

  7. Plasma Concentrations of Binimetinib administered in combination with IDE196

    Pharmacokinetics of Binimetinib in combination with IDE196

    Measured: Approx. 6 months

  8. Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria

    Measured: Approx. 8 months

  9. Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

    RECIST v1.1

    Measured: Approx. 8 months

Secondary outcomes (11)

  1. Progression Free Survival (PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment

    RECIST v1.1

    Measured: Approx. 18 months

  2. Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts and by prior treatment status (pretreated or treatment naive) by Investigator response assessment

    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria

    Measured: Approx. 18 months

  3. Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by prior treatment status (pretreated or treatment naive) by Investigator response assessment

    RECIST v1.1

    Measured: Approx. 18 months

  4. Disease Control Rate (DCR) by Investigator

    RECIST v1.1

    Measured: Approx. 18 months

  5. Area under the plasma concentration versus time curve (AUC)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  6. Area under the plasma concentration curve from time zero extrapolated to infinity (AUCinf)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  7. Area under the plasma concentration curve from time zero to the last measurable concentration time (AUC0-t)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  8. Area under the plasma concentration curve extrapolating the percentage of total drug exposure (AUC%extra)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  9. Peak Plasma Concentration (Cmax)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  10. Time to maximum plasma concentration (Tmax)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

  11. Elimination half-life of Plasma Concentration levels (T1/2)

    PK parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran (dabigtran+glucuronide), and the exposures of PDA (as data permits)

    Measured: Approx. 8 months

Timeline

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

  1. First posted13 May 2019
  2. Study start28 Jun 2019
  3. Primary completion29 Jan 2027 (estimated)
  4. Study completion15 Jun 2027 (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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
336 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03947385
Sponsor's protocol ID
IDE196-001
Status last verified
Jun 2026
First submitted
9 May 2019
Last updated
8 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing IDE196, Binimetinib and Crizotinib in people with Metastatic Uveal Melanoma and Cutaneous Melanoma, run by IDEAYA Biosciences at 15 sites in 3 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 13 inclusion and 29 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: looking for participants now, as of the sponsor's last update on 8 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Australia, Canada. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

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?

Contact IDEAYA Clinical Trials (855-IDEA-BIO (855-433-2246), IDEAYAClinicalTrials@ideayabio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose-limiting Toxicity (DLT) (time frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib). The study lists 9 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 NCT03947385.

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 8 Jun 2026.

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