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

Trial Status: Closed to Accrual

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

Alabama

Birmingham
University of Alabama at Birmingham Cancer Center
Status: ADMINISTRATIVELY_COMPLETE

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Orange
UC Irvine Health / Chao Family Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: COMPLETED

Massachusetts

Boston
Brigham and Women's Hospital
Status: WITHDRAWN
Dana-Farber Cancer Institute
Status: WITHDRAWN
Massachusetts General Hospital Cancer Center
Status: COMPLETED

Minnesota

Rochester
Mayo Clinic in Rochester
Status: CLOSED_TO_ACCRUAL

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: CLOSED_TO_ACCRUAL

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: COMPLETED

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Pfizer Inc

  • Primary ID CMEK162B2301
  • Secondary IDs NCI-2013-01414, C4221004, 2013-001176-38
  • Clinicaltrials.gov ID NCT01909453