Recruiting
Phase 1
Phase 2

IDE196

Sponsor:

IDEAYA Biosciences

Code:

NCT03947385

Conditions

Metastatic Uveal Melanoma

Cutaneous Melanoma

Colorectal Cancer

Other Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

IDE196

Binimetinib

Crizotinib

Study Details

Brief 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 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.

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.

Conditions

Metastatic Uveal Melanoma

Cutaneous Melanoma

Colorectal Cancer

Other Solid Tumors

Study ID

NCT03947385

Start date

Jun 28, 2019

Status verified date

Jun, 2026

Completion date

Jun 15, 2027

Anticipated

Primary completion date

Jan 29, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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-A\*02:01 positive cohort, HLA status must be documented by test results from a CAP/CLIA-certified laboratory.
  • Measurable disease per RECIST v1.1
  • 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.

Exclusion Criteria:

  • 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
  • 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.

Study Design

Enrollment

336 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation Monotherapy (Enrollment Complete)

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

experimental: Dose Expansion Monotherapy (Enrollment Complete)

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

experimental: Dose Escalation Binimetinib Combination (Enrollment Complete)

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

experimental: Dose Expansion Binimetinib Combination (Enrollment Complete)

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

experimental: Dose Escalation Crizotinib Combination (Enrollment Complete)

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

experimental: Dose Expansion Crizotinib Combination (Enrolling)

MUM 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.

experimental: Dose Optimization Crizotinib Combination (Enrollment Complete)

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

experimental: Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete)

Crizotinib 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

Interventions

IDE196

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

Binimetinib

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

Crizotinib

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

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 ]
  • Incidence of Adverse Events [ Time Frame: Approx. 8 months ]
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib ]
  • Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [ Time Frame: Approx. 6 months ]
  • Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [ Time Frame: Approx. 6 months ]
  • Plasma Concentrations of Crizotinib administered in combination with IDE196 [ Time Frame: Approx. 6 months ]
  • Plasma Concentrations of Binimetinib administered in combination with IDE196 [ Time Frame: Approx. 6 months ]
  • Overall Response Rate (ORR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment [ Time Frame: Approx. 8 months ]
  • Duration of Response (DOR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Investigator response assessment [ Time Frame: Approx. 8 months ]

Central Contacts and Locations

Central contacts

IDEAYA Clinical Trials

855-IDEA-BIO (855-433-2246)IDEAYAClinicalTrials@ideayabio.com

Locations

UCLA Medical Center

Recruiting

Los Angeles, California, United States, 90095

Contacts

Bartosz Chmielowski, MD

BChmielowski@mednet.ucla.edu

Principal Investigator:

Bartosz Chmielowski, MD

SCRI - Denver

Recruiting

Denver, Colorado, United States, 80218

Contacts

Ryan Weight, MD

ryan.weight@theskincancerinstitute.com

Principal Investigator:

Ryan Weight, MD

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Carol A Wiggs

cao13@duke.edu

Principal Investigator:

April Salama, MD

University of Cincinnati Cancer Center

Recruiting

Cincinnati, Ohio, United States, 45267

Contacts

513-584-7698

Principal Investigator:

Trisha Wise-Draper, MD

Sidney Kimmel Cancer Center at Thomas Jefferson University

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Contacts

Marlana Orloff, MD

marlana.orloff@jefferson.edu

Principal Investigator:

Marlana Orloff, MD

The Sarah Cannon Research Institute/Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

askSARAH

844-482-4812

Principal Investigator:

Meredith McKean, MD

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Jordi Ahnert, MD

JRodon@mdanderson.org

Principal Investigator:

Jordi Rodon Ahnert, MD

More Information

Sponsor

IDEAYA Biosciences

Last update posted

Jun 8, 2026

Last verified

Jun, 2026

Keywords

  • Metastatic Uveal Melanoma
  • Uveal Melanoma
  • Protein Kinase C
  • Ophthalmology
  • Ocular Oncology
  • Darovasertib
  • IDE196
  • Ocular Melanoma

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by IDEAYA Biosciences on 2026-06-08.