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Trial record 1 of 1 for:    03947385
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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 : November 18, 2023
Sponsor:
Information provided by (Responsible Party):
IDEAYA Biosciences

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. 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.


Condition or disease Intervention/treatment Phase
Metastatic Uveal Melanoma Cutaneous Melanoma Colorectal Cancer Other Solid Tumors Drug: IDE196 Drug: Binimetinib Drug: Crizotinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 278 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 : June 28, 2019
Estimated Primary Completion Date : October 31, 2024
Estimated Study Completion Date : May 31, 2025


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 Name: 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 Name: 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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Binimetinib
Binimetinib dosed orally, twice daily for each 28-day cycle
Other Name: 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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Binimetinib
Binimetinib dosed orally, twice daily for each 28-day cycle
Other Name: 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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: 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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: XALKORI

Experimental: Dose Optimization 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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: XALKORI

Experimental: Crizotinib Monotherapy with Crossover to Combination
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 Name: Protein Kinase C (PKC) Inhibitor

Drug: Crizotinib
Crizotinib dosed orally, twice daily for each 28-day cycle
Other Name: 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 Name: Protein Kinase C (PKC) Inhibitor




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. Plasma Concentrations of Crizotinib administered in combination with IDE196 [ Time Frame: Approx. 6 months ]
    Pharmacokinetics of Crizotinib in combination with IDE196

  6. Plasma Concentrations of Binimetinib administered in combination with IDE196 [ Time Frame: Approx. 6 months ]
    Pharmacokinetics of Binimetinib in combination with IDE196

  7. 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

  8. 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


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 [ Time Frame: 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 [ Time Frame: Approx. 48 months ]
    RECIST v1.1

  3. ORR by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1

  4. Duration of Response by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1

  5. Disease Control by Investigator [ Time Frame: Approx. 48 months ]
    RECIST v1.1

  6. 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

  7. Treatment-related pharmacodynamic effect in all patients [ Time Frame: Approx. 48 months ]
    Modulation of signaling proteins in PKC, MAPK, and MET pathways


Other Outcome Measures:
  1. Progression-Free Survival [ Time Frame: Approx. 48 months ]
    RECIST v1.1

  2. Overall Survival [ Time Frame: Approx. 48 months ]
    From date of First Dose to End of Follow-up

  3. Reduction in tumor burden by total volumetric measurement [ Time Frame: Approx. 48 months ]
    Maximum reduction in tumor burden relative to response

  4. Treatment-related gene signatures and/or molecular profiling [ Time Frame: Approx. 48 months ]
    Modulation of gene signatures and/or molecular profiles

  5. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03947385


Contacts
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Contact: IDEAYA Clinical Trials +1 650 534 3616 IDEAYAClinicalTrials@ideayabio.com

Locations
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United States, Arizona
HonorHealth Research Institute Completed
Scottsdale, Arizona, United States, 85258
United States, California
UCLA Medical Center Recruiting
Los Angeles, California, United States, 90095
Contact: Bartosz Chmielowski, MD       BChmielowski@mednet.ucla.edu   
San Francisco Oncology Associates Recruiting
San Francisco, California, United States, 94115
Contact       clinicalresearch@sutterhealth.org   
United States, Florida
Florida Cancer Specialist South Completed
Fort Myers, Florida, United States, 33901
Florida Cancer Specialist North Completed
Saint Petersburg, Florida, United States, 33705
United States, Missouri
Mosaic Life Care Completed
Saint Joseph, Missouri, United States, 64507
United States, New York
Columbia University Medical Center - Herbert Irving Pavilion Recruiting
New York, New York, United States, 10032
Contact: Shaheer Khan, MD       sk4488@cumc.columbia.edu   
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Carol A Wiggs       cao13@duke.edu   
United States, Ohio
University of Cincinnati Cancer Center Recruiting
Cincinnati, Ohio, United States, 45267
Contact    513-584-7698      
United States, Pennsylvania
Sidney Kimmel Cancer Center at Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Marlana Orloff, MD       marlana.orloff@jefferson.edu   
United States, Tennessee
The Sarah Cannon Research Institute/Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: askSARAH    844-482-4812      
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jordi Ahnert, MD       JRodon@mdanderson.org   
Australia, New South Wales
Westmead Hospital Recruiting
Sydney, New South Wales, Australia
Contact: Matteo Carlino, MD    +61 288 905 200      
Contact    02 8890 5200      
Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, OPG 7-815
Contact: Melissa Da Ponte    416-946-4501 ext 5485    Melissa.DaPonte@uhn.ca   
Sponsors and Collaborators
IDEAYA Biosciences
Investigators
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Study Director: Jasgit Sachdev, MD jsachdev@ideayabio.com
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Responsible Party: IDEAYA Biosciences
ClinicalTrials.gov Identifier: NCT03947385    
Other Study ID Numbers: IDE196-001
First Posted: May 13, 2019    Key Record Dates
Last Update Posted: November 18, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IDEAYA Biosciences:
Metastatic Uveal Melanoma
Uveal Melanoma
Protein Kinase C
Ophthalmology
Ocular Oncology
Darovasertib
IDE196
Ocular Melanoma
Additional relevant MeSH terms:
Layout table for MeSH terms
Melanoma
Neoplasms
Neoplasms by Site
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Skin Neoplasms
Skin Diseases
Crizotinib
Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents