Conditions: Melanoma
Keywords: Melanoma Cutaneous melanoma Skin disease Skin cancer Skin Neoplasms Neoplasm Metastasis BRAF mutant BRAF V600E BRAF V600K Cancer LGX818 MEK162 vemurafenib combination BRAF inhibitor resistance The combination of a selective BRAF- and a MEK1/2-inhibitor Prior immunotherapy MEK inhibitor Phase III Combo 300, Combo 450
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 921
Healthy volunteers: no

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:

1. LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm)
2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or
3. 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:

1. LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or
2. LGX818 300 mg QD monotherapy (denoted as LGX818 arm)

Detailed description:

Arms:
arm 1: LGX818 450 mg QD + MEK162 45 mg BID arm 2: Vemurafenib 960 mg BID arm 3: LGX818 300 mg QD + MEK162 45 mg BID arm 4: LGX818 300 mg QD

Interventions: intervention 1: LGX818 intervention 2: MEK162 intervention 3: vemurafenib
Intervention descriptions: intervention 1: LGX818- Orally 100 mg and 50 mg capsules intervention 2: MEK162- Orally 15 mg tablets intervention 3: Tablets in bottles or blisters 240 mg

Protocol document: