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

Brief Summary:
This is 2-part, randomized, open label, multi-center, parallel group, phase III study comparing the efficacy and safety of LGX818 plus MEK162 to vemurafenib and LGX818 monotherapy in patients with locally advanced unresectable or metastatic melanoma with BRAF V600 mutation. A total of approximately 900 patients will be randomized.

Part 1:
Patients will be randomized in a 1:1:1 ratio to one of 3 treatment arms:
- LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm)
- LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or
- vemurafenib 960 mg BID (denoted as vemurafenib arm)

Part 2:
Patients will be randomized in a 3:1 ratio to one of the 2 treatment arms:
- LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or
- LGX818 300 mg QD monotherapy (denoted as LGX818 arm)


Study Type: Interventional  (Clinical Trial)
Actual Enrollment: 921 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Study Start Date: September 2013
Actual Primary Completion Date: September 2016
Estimated Study Completion Date: January 2024

Arms:
- Experimental: LGX818 450 mg + MEK162
- Active Comparator: Vemurafenib
- Experimental: LGX818 300 mg + MEK162
- Experimental: LGX818