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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Metastatic Uveal Melanoma; Cutaneous Melanoma; Other Solid Tumors
• Intervention / Treatment: Drug: IDE196; Drug: Binimetinib; Drug: Crizotinib

• Study Type: Interventional
• Enrollment (Estimated): 336
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: IDEAYA Clinical Trials; Phone Number: 855-IDEA-BIO (855-433-2246); Email: IDEAYAClinicalTrials@ideayabio.com

Study Locations

• Australia
  • Woolloongabba, Australia, 4102
    • Active, not recruiting
    • Queensland
  • New South Wales
    • Sydney, New South Wales, Australia
      • Active, not recruiting
      • Westmead Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, OPG 7-815
      • Active, not recruiting
      • Princess Margaret Cancer Centre
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Medical Center
      • Contact: Bartosz Chmielowski, MD; Email: BChmielowski@mednet.ucla.edu
      • Principal Investigator: Bartosz Chmielowski, MD
    • San Francisco, California, United States, 94115
      • Active, not recruiting
      • San Francisco Oncology Associates
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • SCRI - Denver
      • Principal Investigator: Ryan Weight, MD
      • Contact: Ryan Weight, MD; Email: ryan.weight@theskincancerinstitute.com
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Active, not recruiting
      • University of Iowa
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Active, not recruiting
      • Cancer Hematology Centers Western Michigan
  • New York
    • New York, New York, United States, 10032
      • Active, not recruiting
      • Columbia University Medical Center - Herbert Irving Pavilion
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Carol A Wiggs; Email: cao13@duke.edu
      • Principal Investigator: April Salama, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati Cancer Center
      • Contact: Phone Number: 513-584-7698
      • Principal Investigator: Trisha Wise-Draper, MD
    • Cleveland, Ohio, United States, 44195
      • Active, not recruiting
      • The Cleveland Clinic Foundation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sidney Kimmel Cancer Center at Thomas Jefferson University
      • Principal Investigator: Marlana Orloff, MD
      • Contact: Marlana Orloff, MD; Email: marlana.orloff@jefferson.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • The Sarah Cannon Research Institute/Tennessee Oncology
      • Contact: askSARAH; Phone Number: 844-482-4812
      • Principal Investigator: Meredith McKean, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Jordi Ahnert, MD; Email: JRodon@mdanderson.org
      • Principal Investigator: Jordi Rodon Ahnert, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Monotherapy (Enrollment Complete); IDE196 dosed orally, twice daily (BID) for each 28-day cycle	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor
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)	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor
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	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Binimetinib; Binimetinib dosed orally, twice daily for each 28-day cycle; Other Names: MEKTOVI
Experimental: Dose Expansion Binimetinib Combination (Enrollment Complete); RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Binimetinib; Binimetinib dosed orally, twice daily for each 28-day cycle; Other Names: MEKTOVI
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	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Crizotinib; Crizotinib dosed orally, twice daily for each 28-day cycle; Other Names: XALKORI
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.	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Crizotinib; Crizotinib dosed orally, twice daily for each 28-day cycle; Other Names: XALKORI
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	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Crizotinib; Crizotinib dosed orally, twice daily for each 28-day cycle; Other Names: XALKORI
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	Drug: IDE196; IDE196 dosed orally, twice daily for each 28-day cycle; Other Names: Protein Kinase C (PKC) Inhibitor; Drug: Crizotinib; Crizotinib dosed orally, twice daily for each 28-day cycle; Other Names: XALKORI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting Toxicity (DLT)	Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Maximum Tolerated Dose (MTD)	Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	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	Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	Approx. 6 months
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	Approx. 6 months
Plasma Concentrations of Crizotinib administered in combination with IDE196	Pharmacokinetics of Crizotinib in combination with IDE196	Approx. 6 months
Plasma Concentrations of Binimetinib administered in combination with IDE196	Pharmacokinetics of Binimetinib in combination with IDE196	Approx. 6 months
Incidence of Adverse Events	Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	Approx. 8 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	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria	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	RECIST v1.1	Approx. 8 months
Phramacokinetic parameters of bupropion, hydroxybupropion, repaglinide, flurbiprofen, omeprazole, midazolam, total dabigatran, and the exposures of pyridoxic acid by IDE196 monotherapy and IDE196 in combination with Crizotinib	PK parameters of drug cocktail	Approx. 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Approx. 18 months
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	Approx. 18 months
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	Approx. 18 months
Disease Control Rate (DCR) by Investigator	RECIST v1.1	Approx. 18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	From date of First Dose to End of Follow-up	Approx. 18 months
Anti-tumor activity (ORR/DOR/PFS) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in Dose Expansion cohorts by Blinded Independent Review Committee (BICR)	RECIST v1.1	Approx. 18 months
Anti-tumor activity (ORR/DOR/DCR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in phase 1 Dose Escalation cohorts by Investigator response assessment	RECIST v1.1	Approx. 18 months
Anti-tumor activity (ORR/DOR/DCR) of IDE196 monotherapy, in combination with Binimetinib, and in combination with Crizotinib in pre-treated participants by Investigator response assessment	RECIST v1.1	Approx. 18 months
Treatment-related gene signatures and/or molecular profiling	Modulation of gene signatures and/or molecular profiles	Approx. 18 months
Treatment-related pharmacodynamic effect in all patients	Modulation of signaling proteins in PKC, MAPK, and MET pathways	Approx. 18 months
Treatment-related changes in tumor tissue or cell-free DNA from blood	Modulation of tissue or cell-free DNA expression	Approx. 18 months
Metabolite profile of IDE196 in plasma	Exploratory assessment of IDE196 metabolite profiling the plasma	Approx. 18 months
Impact on pravastatin PK profile by IDE196 and Crizotinib combination	PK parameters of pravastatin	Approx. 18 months

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences
• Investigators: Study Director: George Cole Jr., MD, gcole@ideayabio.com

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2019
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): June 15, 2027

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 13, 2019

Study Record Updates

• Last Update Posted (Actual): January 27, 2026
• Last Update Submitted That Met QC Criteria: January 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Uveal Melanoma; Ocular Melanoma; Ophthalmology; Ocular Oncology; Metastatic Uveal Melanoma; Protein Kinase C; Darovasertib; IDE196
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Eye Diseases; Colonic Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Eye Neoplasms; Uveal Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Colorectal Neoplasms; Melanoma; Uveal Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Enzymes; Enzymes and Coenzymes; Piperidines; Aminopyridines; Transferases; Protein Serine-Threonine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Intracellular Signaling Peptides and Proteins; Crizotinib; binimetinib; Protein Kinase C
• Other Study ID Numbers: IDE196-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No