Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma

Inclusion Criteria:

- Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or
unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV)

- Presence of BRAF V600E or V600K mutation in tumor tissue prior to randomization

- Naïve untreated patients or patients who have progressed on or after prior first line
immunotherapy for resectable locally advanced or metastatic melanoma; prior adjuvant
therapy is permitted (e.g. IFN, IL-2 therapy, any other immunotherapy, radiotherapy or
chemotherapy), except the administration of BRAF or MEK inhibitors

- Evidence of at least one measurable lesion as detected by radiological or photographic
methods

- ECOG performance status of 0 or 1

- Adequate bone marrow, organ function, cardiac and laboratory parameters

- Normal functioning of daily living activities

Exclusion Criteria:

- Any untreated central nervous system (CNS) lesion

- Uveal and mucosal melanoma

- History of leptomeningeal metastases

- History of or current evidence of central serous retinopathy (CSR), retinal vein
occlusion (RVO) or history of retinal degenerative disease

- Any previous systemic chemotherapy treatment, extensive radiotherapy or
investigational agent other than immunotherapy, or patients who have received more
than one line of immunotherapy for locally advanced unresectable or metastatic
melanoma; Ipilimumab (adjuvant) or other immunotherapy treatment must have ended at
least 6 weeks prior to randomization

- History of Gilbert's syndrome

- Prior therapy with a BRAF inhibitor and/or a MEK- inhibitor

- Impaired cardiovascular function or clinically significant cardiovascular diseases

- Uncontrolled arterial hypertension despite medical treatment

- HIV positive or active Hepatitis B, and/or active Hepatitis C

- Impairment of gastrointestinal function

- Patients with neuromuscular disorders that are associated with elevated CK

- Pregnant or nursing (lactating) women

- Medical, psychiatric, cognitive or other conditions that may compromise the patient's
ability to understand the patient information, give informed consent, comply with the
study protocol or complete the study

Other protocol-defined inclusion/exclusion criteria may apply