Overview

This trial is active, not recruiting.

Condition melanoma
Treatments lgx818, mek162, vemurafenib
Phase phase 3
Targets RAF, BRAF, MEK
Sponsor Array BioPharma
Start date September 2013
End date September 2016
Trial size 921 participants
Trial identifier NCT01909453, CMEK162B2301

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)

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
LGX818 450 mg QD + MEK162 45 mg BID
lgx818
LGX818- Orally 100 mg and 50 mg capsules
mek162
MEK162- Orally 15 mg tablets
(Active Comparator)
Vemurafenib 960 mg BID
vemurafenib Zelboraf
Tablets in bottles or blisters 240 mg
(Experimental)
LGX818 300 mg QD + MEK162 45 mg BID
lgx818
LGX818- Orally 100 mg and 50 mg capsules
mek162
MEK162- Orally 15 mg tablets
(Experimental)
LGX818 300 mg QD
lgx818
LGX818- Orally 100 mg and 50 mg capsules

Primary Outcomes

Measure
Progression free survival (PFS)
time frame: Approximately 2 years after first patient randomized

Secondary Outcomes

Measure
Overall Survival (OS)
time frame: Up to approximately 5 years after first patient randomized
Progression Free Survival (PFS)
time frame: Approximately 2 years with update around 3 years after first patient randomized
Objective Response Rate (ORR)
time frame: Approximately 2 years after first patient randomized
Time To Response (TTR)
time frame: Approximately 2 years after first patient randomized
Disease Control Rate (DCR)
time frame: Approximately 2 years after first patient randomized
Duration of objective response (DOR)
time frame: Approximately 2 years after first patient randomized
Safety and tolerability of combination and LGX818
time frame: Up to approximately 4 years after first patient randomized
ECOG Performance status (PS)
time frame: Approximately 2 years after first patient randomized
Time to definitive 1 point deterioration in ECOG performance status
time frame: Approximately 2 years after first patient randomized
Pharmacokinetics of LGX818 and MEK162
time frame: Approximately 2 years after first patient randomized
Time to definitive 10% deterioration in global health status (EORTC QLQC30)
time frame: Approximately 2 years after first patient randomized
Global health status (EORTC QLQC30)
time frame: Approximately 2 years after first patient randomized
Time to definitive 10% deterioration in the FACT-M melanoma subscale
time frame: Approximately 2 years after first patient randomized
Global health status (EQ-5D)
time frame: Approximately 2 years after first patient randomized

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

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
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Array BioPharma.