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

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

Tracking Information

• First Submitted Date: May 9, 2019
• First Posted Date: May 13, 2019
• Last Update Posted Date: May 12, 2022
• Actual Study Start Date: June 28, 2019
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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

Current Secondary Outcome Measures (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 (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: Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions
• Official Title: 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: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Metastatic Uveal Melanoma
• Cutaneous Melanoma
• Colorectal Cancer
• Other Solid Tumors

Intervention

• 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

• 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

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 15, 2021): 254
• Original Estimated Enrollment (submitted: May 9, 2019): 166
• Estimated Study Completion Date: December 31, 2023
• Estimated Primary Completion Date: December 31, 2022 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, Canada, United States

Administrative Information

• NCT Number: NCT03947385
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: IDEAYA Biosciences
• Original Responsible Party: Same as current
• Current Study Sponsor: IDEAYA Biosciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: IDEAYA Biosciences
• Verification Date: December 2021