MEK162 in Combination With Imatinib Mesylate in Patients With Untreated Advanced Gastrointestinal Stromal Tumor (GIST)

Inclusion Criteria: * Patients must have pathologically confirmed GIST. * In the Phase Ib portion, must have locally advanced or metastatic GIST and have progressed on imatinib. * In the Phase II portion, patients must be newly diagnosed or treatment naïve, or have been off adjuvant imatinib therapy for at least 3 months. Patients with newly diagnosed GIST and who had been on imatinib for up to 4 weeks prior to signing the consent are allowed to enroll in order to expedite accrual. * Patients must be at least 18 years of age. * Disease must be measurable by RECIST 1.1. * ECOG Performance Status 0 or 1. * Adequate renal, hepatic, and hematologic function as the following: Serum Creatinine ≤ 1.5 mg/dL, Total Serum Bilirubin ≤ 1.5 x upper limit of normal (ULN), Serum AST (SGOT) and/or ALT (SGPT) ≤ 2.5 x ULN (or ≤ 5.0 x ULN if considered due to tumor)ANC ≥ 1500/mm3, Platelets ≥ 100,000/mm3, and hemoglobin ≥ 10g/dL. * Patients of childbearing potential must have a negative serum pregnancy test within 14 days of treatment. Patients must agree to use a reliable barrier method of birth control during and for 3 months following the last dose of study drug. * Patient must have adequate cardiac function (left ventricular ejection fraction (LVEF) ≥50% as determined by a multigated acquisition (MUGA) scan or echocardiogram; and QTc interval≤480 ms. * Patient must be able to take oral medications. * Patients must sign an informed consent document. Exclusion Criteria: * In the phase II p…