Open
Actively Recruiting
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
Study Type
Phase
Eligibility
Gender
Healthy Volunteers
Minimum Age
Maximum Age
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
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Study Stats
Protocol No.
19-001970
Category
Melanoma (Skin Cancer)
Other Cancer
Principal Investigator
Contact
Location
- UCLA Westwood