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 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.

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): 278
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: IDEAYA Clinical Trials; Phone Number: +1 650 534 3616; Email: IDEAYAClinicalTrials@ideayabio.com

Study Locations

• Australia
  • New South Wales
    • Sydney, New South Wales, Australia
      • Recruiting
      • Westmead Hospital
      • Contact: Matteo Carlino, MD; Phone Number: +61 288 905 200
      • Contact: Phone Number: 02 8890 5200
• Canada
  • Ontario
    • Toronto, Ontario, Canada, OPG 7-815
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Melissa Da Ponte; Phone Number: 5485 416-946-4501; Email: Melissa.DaPonte@uhn.ca
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Completed
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA Medical Center
      • Contact: Bartosz Chmielowski, MD; Email: BChmielowski@mednet.ucla.edu
    • San Francisco, California, United States, 94115
      • Recruiting
      • San Francisco Oncology Associates
      • Contact: Email: clinicalresearch@sutterhealth.org
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Completed
      • Florida Cancer Specialist South
    • Saint Petersburg, Florida, United States, 33705
      • Completed
      • Florida Cancer Specialist North
  • Missouri
    • Saint Joseph, Missouri, United States, 64507
      • Completed
      • Mosaic Life Care
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center - Herbert Irving Pavilion
      • Contact: Shaheer Khan, MD; Email: sk4488@cumc.columbia.edu
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Carol A Wiggs; Email: cao13@duke.edu
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Recruiting
      • University of Cincinnati Cancer Center
      • Contact: Phone Number: 513-584-7698
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Sidney Kimmel Cancer Center at Thomas Jefferson University
      • 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
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
      • Contact: Jordi Ahnert, MD; Email: JRodon@mdanderson.org

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

• 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

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

9

Arms and Interventions

Participant Group / 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
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 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; 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
Overall Response Rate (ORR) for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria	Approx. 48 months
Duration of Response for combination with Binimetinib or in combination with Crizotinib Dose Expansion by Blinded Independent Review Committee	RECIST v1.1	Approx. 48 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria	Approx. 48 months
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	RECIST v1.1	Approx. 48 months
ORR by Investigator	RECIST v1.1	Approx. 48 months
Duration of Response by Investigator	RECIST v1.1	Approx. 48 months
Disease Control by Investigator	RECIST v1.1	Approx. 48 months
Numbers of Participants with Adverse Events	Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib	Approx. 48 months
Treatment-related pharmacodynamic effect in all patients	Modulation of signaling proteins in PKC, MAPK, and MET pathways	Approx. 48 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival	RECIST v1.1	Approx. 48 months
Reduction in tumor burden by total volumetric measurement	Maximum reduction in tumor burden relative to response	Approx. 48 months
Treatment-related gene signatures and/or molecular profiling	Modulation of gene signatures and/or molecular profiles	Approx. 48 months
Treatment-related changes in tumor tissue or cell-free DNA from blood	Modulation of tissue or cell-free DNA expression	Approx. 48 months
Overall Survival	From date of First Dose to End of Follow-up	Approx. 48 months

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences
• Investigators: Study Director: Jasgit Sachdev, MD, jsachdev@ideayabio.com

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2019
• Primary Completion (Estimated): October 31, 2024
• Study Completion (Estimated): May 31, 2025

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 (Estimated): November 20, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: November 1, 2023

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 Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• 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