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