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

About

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.

Primary Purpose
Treatment
Study Type
Interventional
Phase
Phase I/II

Eligibility

Gender
All
Healthy Volunteers
No
Minimum Age
18 Years
Maximum Age
N/A

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:

  • Another malignancy
  • 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
  • Untreated or symptomatic central nervous system metastases
  • Human immunodeficiency virus, acquired immunodeficiency syndrome related illness, hepatitis B virus, or hepatitis C virus
  • Recent surgery or radiotherapy
  • Females who are pregnant or breastfeeding
  • Impaired cardiac function
  • For patients receiving IDE196 powder-in-capsule (PIC) formulation or crizotinib, allergy to mammalian meat products and gelatin

Binimetinib Combination Additional Exclusion Criteria

  • Patient has received prior treatment with a MEK inhibitor
  • History of interstitial lung disease
  • History of thromboembolic or cerebrovascular events ≤ 12 weeks prior to first dose
  • History or current evidence of central serous retinopathy (CSR) or retinal vein occlusion (RVO); History of retinal degenerative disease
  • Concurrent neuromuscular disorders that are associated with elevated creatine phosphokinase (CPK)
  • Uncontrolled arterial hypertension despite medical treatment
  • Allergy to binimetinib or its components

Crizotinib Combination Additional Exclusion Criteria:

  • Prior therapy directly targeting ALK, MET, or ROS1
  • Spinal cord compression
  • Carcinomatous meningitis or leptomeningeal disease
  • History of pneumonitis or interstitial lung disease

Join this Trial

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Study Stats
Protocol No.
19-001970
Category
Hematology-Oncology
Oncology
Contact
Banafsheh Sinaki
Location
  • UCLA Westwood
For Providers
NCT No.
NCT03947385
For detailed technical eligibility, visit ClinicalTrials.gov.