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

Sponsor
IDEAYA Biosciences (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03947385
Collaborator
(none)
254
Enrollment
14
Locations
7
Arms
54.1
Anticipated Duration (Months)
18.1
Patients Per Site
0.3
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
254 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
Actual Study Start Date :
Jun 28, 2019
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation Monotherapy

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

    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

    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

    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

    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

    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: Crizotinib
    Crizotinib dosed orally, twice daily for each 28-day cycle
    Other Names:
  • XALKORI

    		•
    Experimental: Tablet PK Substudy

    IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, 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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Dose-limiting Toxicity (DLT) [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

    2. Maximum Tolerated Dose (MTD) [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

    3. Recommended Phase 2 Dose (RP2D) as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [Approx. 6 months]

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

    4. Plasma Concentrations of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib [Approx. 6 months]

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

    5. Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee [Approx. 48 months]

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

    6. Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee [Approx. 48 months]

      RECIST v1.1

    Secondary Outcome Measures

    1. 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 [Approx. 48 months]

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

    2. 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 [Approx. 48 months]

      RECIST v1.1

    3. ORR by Investigator [Approx. 48 months]

      RECIST v1.1

    4. Duration of Response by Investigator [Approx. 48 months]

      RECIST v1.1

    5. Disease Control by Investigator [Approx. 48 months]

      RECIST v1.1

    6. Numbers of Participants with Adverse Events [Approx. 48 months]

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

    7. Treatment-related pharmacodynamic effect in all patients [Approx. 48 months]

      Modulation of signaling proteins in PKC, MAPK, and MET pathways

    Other Outcome Measures

    1. Progression-Free Survival [Approx. 48 months]

      RECIST v1.1

    2. Overall Survival [Approx. 48 months]

    3. Reduction in tumor burden by total volumetric measurement [Approx. 48 months]

      Maximum reduction in tumor burden relative to response

    4. Treatment-related gene signatures and/or molecular profiling [Approx. 48 months]

      Modulation of gene signatures and/or molecular profiles

    5. Treatment-related changes in tumor tissue or cell-free DNA from blood [Approx. 48 months]

      Modulation of tissue or cell-free DNA expression

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Research Institute Scottsdale Arizona United States 85258
    2 UCLA Medical Center Los Angeles California United States 90095
    3 San Francisco Oncology Associates San Francisco California United States 94115
    4 Florida Cancer Specialist South Fort Myers Florida United States 33901
    5 Florida Cancer Specialist North Saint Petersburg Florida United States 33705
    6 Mosaic Life Care Saint Joseph Missouri United States 64507
    7 Columbia University Medical Center - Herbert Irving Pavilion New York New York United States 10032
    8 Duke University Medical Center Durham North Carolina United States 27710
    9 University of Cincinnati Cancer Center Cincinnati Ohio United States 45267
    10 Sidney Kimmel Cancer Center at Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    11 The Sarah Cannon Research Institute/Tennessee Oncology Nashville Tennessee United States 37203
    12 The University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    13 Westmead Hospital Sydney New South Wales Australia
    14 Princess Margaret Cancer Centre Toronto Ontario Canada OPG 7-815

    Sponsors and Collaborators

    • IDEAYA Biosciences

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    IDEAYA Biosciences
    ClinicalTrials.gov Identifier:
    NCT03947385
    Other Study ID Numbers:
    • IDE196-001
    First Posted:
    May 13, 2019
    Last Update Posted:
    May 12, 2022
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Melanoma
    Crizotinib

    Study Results

    No Results Posted as of May 12, 2022