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

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ClinicalTrials.gov Identifier: NCT03947385
Recruitment Status : Recruiting
First Posted : May 13, 2019
Last Update Posted : May 12, 2022
Sponsor:
Information provided by (Responsible Party):
IDEAYA Biosciences

Tracking Information
First Submitted Date  ICMJE May 9, 2019
First Posted Date  ICMJE May 13, 2019
Last Update Posted Date May 12, 2022
Actual Study Start Date  ICMJE June 28, 2019
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 21, 2021)
  • Dose-limiting Toxicity (DLT) [ Time Frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib ]
    Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib ]
    Determine MTD 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 ]
    Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
  • Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [ Time Frame: Approx. 6 months ]
    Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
  • Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee [ Time Frame: Approx. 48 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
  • Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee [ Time Frame: Approx. 48 months ]
    RECIST v1.1
Original Primary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Dose-limiting Toxicity (DLT) [ Time Frame: 28 days following first dose of IDE196 ]
    Determine DLT of IDE196
  • Maximum Tolerated Dose (MTD) [ Time Frame: 28 days following first dose of IDE196 ]
    Determine MTD of IDE196
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Approx. 6 months ]
    Determine RP2D of IDE196
  • Plasma Concentrations of IDE196 [ Time Frame: Cycle 1 Day 1 (C1D1), C1D15, C2D1, C3D1, C4D1, C5D1, C6D1 ]
    Pharmacokinetics of IDE196
  • Overall Response Rate (ORR) in Dose Expansion [ Time Frame: Approx. 30 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2021)
  • Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and all combination cohorts by Blinded Independent Review Committee [ Time Frame: Approx. 48 months ]
    Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
  • Duration of Response for combination with Binimetinib or in combination with Crizotinib in Dose Escalation and in all combination cohorts by Blinded Independent Review Committee [ Time Frame: Approx. 48 months ]
    RECIST v1.1
  • ORR by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1
  • Duration of Response by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1
  • Disease Control by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1
  • Numbers of Participants with Adverse Events [ Time Frame: Approx. 48 months ]
    Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
  • Treatment-related pharmacodynamic effect in all patients [ Time Frame: Approx. 48 months ]
    Modulation of signaling proteins in PKC, MAPK, and MET pathways
Original Secondary Outcome Measures  ICMJE
 (submitted: May 9, 2019)
  • Duration of Response [ Time Frame: Approx. 30 months ]
    RECIST version 1.1
  • Disease Control [ Time Frame: Approx. 30 months ]
    RECIST version 1.1
  • Numbers of Participants with Adverse Events [ Time Frame: Approx. 48 months ]
    Safety and tolerability of IDE196
Current Other Pre-specified Outcome Measures
 (submitted: December 21, 2021)
  • Progression-Free Survival [ Time Frame: Approx. 48 months ]
    RECIST v1.1
  • Overall Survival [ Time Frame: Approx. 48 months ]
  • Reduction in tumor burden by total volumetric measurement [ Time Frame: Approx. 48 months ]
    Maximum reduction in tumor burden relative to response
  • Treatment-related gene signatures and/or molecular profiling [ Time Frame: Approx. 48 months ]
    Modulation of gene signatures and/or molecular profiles
  • Treatment-related changes in tumor tissue or cell-free DNA from blood [ Time Frame: Approx. 48 months ]
    Modulation of tissue or cell-free DNA expression
Original Other Pre-specified Outcome Measures
 (submitted: May 9, 2019)
  • Overall Survival [ Time Frame: Approx. 48 months ]
  • Progression-Free Survival [ Time Frame: Approx. 48 months ]
 
Descriptive Information
Brief Title  ICMJE Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Official Title  ICMJE A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
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 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Uveal Melanoma
  • Cutaneous Melanoma
  • Colorectal Cancer
  • Other Solid Tumors
Intervention  ICMJE
  • Drug: IDE196
    IDE196 dosed orally, twice daily for each 28-day cycle
    Other Name: Protein Kinase C (PKC) Inhibitor
  • Drug: Binimetinib
    Binimetinib dosed orally, twice daily for each 28-day cycle
    Other Name: MEKTOVI
  • Drug: Crizotinib
    Crizotinib dosed orally, twice daily for each 28-day cycle
    Other Name: XALKORI
Study Arms  ICMJE
  • Experimental: Dose Escalation Monotherapy
    IDE196 dosed orally, twice daily (BID) for each 28-day cycle
    Intervention: Drug: IDE196
  • Experimental: Dose Expansion Monotherapy
    RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)
    Intervention: Drug: IDE196
  • Experimental: Dose Escalation Binimetinib Combination
    IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle
    Interventions:
    • Drug: IDE196
    • Drug: Binimetinib
  • Experimental: Dose Expansion Binimetinib Combination
    RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
    Interventions:
    • Drug: IDE196
    • Drug: Binimetinib
  • Experimental: Dose Escalation Crizotinib Combination
    IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle
    Interventions:
    • Drug: IDE196
    • Drug: Crizotinib
  • Experimental: Dose Expansion Crizotinib Combination
    RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)
    Interventions:
    • Drug: IDE196
    • Drug: Crizotinib
  • Experimental: Tablet PK Substudy
    IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle
    Intervention: Drug: IDE196
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 15, 2021)
254
Original Estimated Enrollment  ICMJE
 (submitted: May 9, 2019)
166
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patient must be ≥18 years of age
  • Diagnosis of one of the following:

    • MUM: Uveal melanoma with histological or cytological confirmed metastatic disease. Or
    • Non-MUM: Advanced cutaneous melanoma, colorectal cancer, or other solid tumor that has progressed following prior standard therapies or that has no satisfactory alternative therapies and has evidence of GNAQ/11 hotspot mutation
  • Measurable disease
  • 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

Binimetinib Combination Additional Inclusion Criteria:

• Adequate cardiac function represented by left ventricular ejection fraction (LVEF) ≥ 50%

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

Exclusion Criteria:

  • Known symptomatic brain metastases
  • Previous treatment with a PKC inhibitor
  • Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors
  • 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

Binimetinib Combination Additional Exclusion Criteria

  • Prior treatment with a MEK inhibitor
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • History of interstitial lung disease
  • History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to first dose
  • Concurrent neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK)
  • Uncontrolled arterial hypertension despite medical treatment
  • Allergy to binimetinib or its components
  • History of syncope

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: IDEAYA Clinical Trials +1 650 534 3616 IDEAYAClinicalTrials@ideayabio.com
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03947385
Other Study ID Numbers  ICMJE IDE196-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party IDEAYA Biosciences
Original Responsible Party Same as current
Current Study Sponsor  ICMJE IDEAYA Biosciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account IDEAYA Biosciences
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP