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

Inclusion Criteria

• Inclusion Criteria (All): - Written informed consent must - Patient has histologically and/or cytologically confirmed malignancies: Phase I: • Patients with advanced or metastatic solid tumors who have failed at least one prior line of systemic antineoplastic therapy in the advanced setting without a standard of care treatment option available; Phase II: - Advanced or metastatic pancreatic adenocarcinoma who have failed at least one prior systemic antineoplastic therapies in the advanced setting - Advanced or metastatic KRAS-mutant CRC who have failed at least two prior systemic antineoplastic therapies in the advanced setting without a standard of care treatment option available. Testing for KRAS mutation in patients with CRC using locally approved diagnostic kit will be used for eligibility. - Phase II only: patient must have measurable disease - Patient has an ECOG performance status 0 or 1. - Patient has adequate bone marrow and organ function - Patient must have specified laboratory values within normal limits or corrected to within normal limits with supplements before the first dose of study medication on Cycle 1 Day 1: - Standard 12-lead ECG values defined 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) Other protocol-defined inclusion/exclusion criteria may apply.