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

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