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

Open to people ages 18 years and up

• 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

• 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