Study of Safety and Efficacy of Ribociclib and Trametinib in Patients With Metastatic or Advanced Solid Tumors

Exclusion Criteria

• •Phase II only:
• •Patient has received prior treatment with a MEK inhibitor or a CDK4/6 inhibitor.
• •Phase I and Phase II:
• •Patient with a known hypersensitivity to the study drugs or any of the excipients of ribociclib or trametinib.
• •Patient is concurrently using other anti-cancer therapy.
• •Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to Cycle 1 Day 1
• •Patient has received local therapy to liver ≤ 3 months of C1D1
• •History of liver disease as follow:
• •Cirrhosis
• •Autoimmune hepatitis
• •Active viral hepatitis
• •Portal hypertension
• •Drug induced liver steatosis
• •Prior systemic anti-cancer treatment within 28 days prior to Cycle 1 Day 1
• •Prior therapy with anthracyclines at cumulative doses of 450 mg/ m2 or more for doxorubicin or 900 mg/m2 or more for epirubicin.
• •Patient is currently receiving warfarin or other coumadin derived anti-coagulant
• •Patient has a history of deep venin thrombosis or pulmonary embolism within 6 months of screening.
• •Patient has a concurrent malignancy or malignancy within 3 years prior to Cycle 1 Day 1, with the exception of adequately treated basal or squamous cell carcinoma or curatively resected cervical cancer.
• •Patients with central nervous system (CNS) involvement
• •Patient has impairment of GI function or GI disease that may significantly alter the absorption of the study drugs
• •History of interstitial lung disease or pneumonitis.
• •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
• •Patient is currently receiving any strong inducers or inhibitors of CYP3A4/5 and/or Substances that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 and cannot be discontinued 7 days prior to Cycle 1 Day 1:
• •Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.
• •History of retinal vein occlusion (RVO)