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

Exclusion Criteria

• •Previous treatment with a PKC inhibitor
• •Known MSI-H/dMMR tumors who have not previously received immune checkpoint inhibitors
• •Known symptomatic brain metastases
• •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
• •Prior therapy directly targeting ALK, MET, or ROS1
• •Spinal cord compression
• •History of pneumonitis or interstitial lung disease
• •History of syncope
• •History of thromboembolic or cerebrovascular events ≤12 weeks prior to first dose of study treatment
• •Taken any dose of statin or inhibitor of organic anion transporting polypeptide within 7 days prior to enrollment in the study and cannot refrain from them through C2D1
• •Taken drugs that interfere with the absorption, metabolism, or elimination of pravastatin
• •Any contraindication associated to the use of statins or hypersensitivity component of pravastatin
• •Active liver disease
• •Treatment with bupropion, repaglinide, flurbiprofen, omeprazole, esomeprazole, midazolam, and dabigatran etexilate within 7 days prior to Cycle 1 Day -1.
• •Intake of vitamin supplements containing Vitamin B6 (pyridoxine), grapefruit/grapefruit juice, or Seville orange juice within 7 days prior to Cycle 1 Day -1.
• •Intake of any strong or moderate inhibitor of CYP2B6, CYP2CI, CYP2C9, CYP2C10 and OAT3 is prohibited within 7 days or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
• •Moderate and strong inhibitors of CYP2A4/5 or P-gp are prohibited within 7 days, or within 5 half-lives, whichever is longer, of Cycle 1 Day -1.
• •Intake of strong or moderate inducers of CYP3A4/5, CYP2B6, CYP2C9, CYP2C19, or OAT3 is prohibited during 15 days, or 5 half-lives, whichever is longer, prior to Cycle 1 Day -1.