LGX818 in Combination With Agents (MEK162; BKM120; LEE011; BGJ398; INC280) in Advanced BRAF Melanoma

Inclusion Criteria: * locally advanced or metastatic melanoma * confirmed BRAF V600 mutation * patients naïve to a selective BRAF inhibitor * fresh tumor biopsy at baseline, and patient agrees for a mandatory biopsy at the time of relapse * life expectancy ≥ 3 months * World Health Organization (WHO) Performance Status ≤ 2. Exclusion Criteria: * Previous treatment with RAF-inhibitor * Symptomatic or untreated leptomeningeal disease * Symptomatic brain metastases. * Known acute or chronic pancreatitis * Clinically significant cardiac disease * AST/SGOT and ALT/SGPT \> 2.5 x ULN, or \> 5 x ULN if liver metastases are present * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral interventional drug * Previous or concurrent malignancy. * Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation Specific exclusion criteria for each treatment arm: LGX818/MEK162: History or current evidence of retinal disease History of Gilbert's syndrome. LGX818/BKM120: Patients with diabetes mellitus requiring insulin treatment Patient has mood disorders LGX818/BGJ398: History and/or current evidence of ectopic mineralization/ calcification Current evidence of corneal disorder/ keratopathy Patients with current evidence of endocrine alteration of calcium/phosphate homeostasis. History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry. Ionized (i) calcium (Ca) \> ULN Serum inorganic phosphorus (Pi) \> ULN LGX818/LEE011 History of congenital long QT- syndrome and/or hypokalaemia CTCAE Grade ≥ 3 and/or magnesium levels below the clinically relevant lower limits before study entry.