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

Status:	Active, not recruiting
Conditions:	Skin Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - Any
Updated:	3/29/2019
Start Date:	September 2013
End Date:	March 31, 2019

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

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)

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

We found this trial at

sites

Meridian Health Systems

Brick, New Jersey 08724

from

Brick, NJ