MEK162 and RAF265 in Adult Patients With Advanced Solid Tumors Harboring RAS or BRAFV600E Mutations

Inclusion criteria

Patients with histologically or cytologically confirmed and non-resectable advanced solid tumors for which no further effective standard therapy exists.

• The patients' tumors must contain documented activating somatic BRAFV600E* , NRAS or KRAS mutations (except for pancreatic cancer)
• All patients enrolled MUST provide fresh or archival tumor samples at baseline to enable central confirmation of BRAF or KRAS/NRAS mutations
• Measurable, or non-measurable but evaluable disease as determined by RECIST
• Adequate bone marrow function
• Adequate hepatic and renal function
• Adequate cardiovascular function
• Negative serum β HCG test (female patients of childbearing potential only) within 72 hrs prior to first dose

Exclusion criteria

• Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases
• Current evidence of retinal disease; or ophthalmopathy as assessed by ophthalmologic examination at baseline that would be considered a risk factor for CSR/RVO (e.g., optic disc cupping, visual field defects, IOP > 21 mm Hg)
• Impaired cardio-/vascular function or clinically significant cardiovascular diseases, including any of the following:

• History/evidence of acute coronary syndromes (including MI, unstable angina, CABG, coronary angioplasty, or stenting) ≤ 6 months prior to starting study drugs
• Thromboembolic event (DVT, CVA, PE) ≤ 6 months prior to starting study
• Symptomatic CHF, history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality
• Uncontrolled arterial hypertension, defined as BP > 140/100 mmHg (average of 3 consecutive readings)
• History of melena, hematemesis or hemoptysis within the last 3 months
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL)

Other protocol-defined inclusion/exclusion criteria may apply