NCT01909453|CompletedPhase 3ResultsDMC

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

COLUMBUS

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

Pfizer ClinicalTrials.gov

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3 other identifiers

CMEK162B23012013-001176-38C4221004

Study Type

interventional

Target

921

Locations

29 countries

Sites

282

Timeline

RegisteredJul 2013

StartedSep 2013

CompletionSep 2024

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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

921

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Sep 2013

Longer than P75 for phase_3

Geographic Reach

29 countries

282 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

11 years study duration

First Submitted

Initial submission to the registry

July 24, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

July 26, 2013

Completed

2 months until next milestone

Study Start

First participant enrolled

September 12, 2013

Completed

3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 9, 2016

Completed

4.7 years until next milestone

Results Posted

Study results publicly available

July 12, 2021

Completed

3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 3, 2024

Completed

Last Updated

February 27, 2026

Status Verified

February 1, 2026

Enrollment Period

3.2 years

First QC Date

July 24, 2013

Results QC Date

May 5, 2021

Last Update Submit

February 9, 2026

Conditions

Melanoma

Keywords

MelanomaCutaneous melanomaSkin diseaseSkin cancerSkin NeoplasmsNeoplasm MetastasisBRAF mutantBRAF V600EBRAF V600KCancerLGX818MEK162vemurafenibcombinationBRAF inhibitorresistanceThe combination of a selective BRAF- and a MEK1/2-inhibitorPrior immunotherapyMEK inhibitorPhase IIICombo 300, Combo 450

Outcome Measures

Primary Outcomes (2)

Part 1: Progression Free Survival (PFS) by BIRC in Combo 450 Group as Compared to Vemurafenib Group
PFS was defined as the time from the date of randomization to the date of the first documented disease progression (PD) or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC/central review and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 square millimeter (mm\^2).
From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
Part 1: PFS by BIRC in Combo 450 Group as Compared to LGX818 Group
PFS was defined as the time from the date of randomization to the date of the first documented PD or death due to any cause, whichever occurs first. PFS was determined based on tumor assessment (RECIST version 1.1 criteria) as per BIRC and survival information. If a participant did not had an event at the time of the analysis cut-off or at the start of any new anti-cancer therapy, data was censored at the date of last adequate tumor assessment. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm\^2.
From randomization until documented PD, initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group

Secondary Outcomes (35)

Part 2: PFS by BIRC in Combo 300 Group as Compared to LGX818 Group
From randomization until documented PD, initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
Part 1: Overall Survival (OS)
From randomization until censoring date/death, whichever occurred first (up to 117.8 months [M] of treatment exposure for LGX818 +MEK162; up to 111.4 months of treatment exposure for LGX818; up to 110.5 months of treatment exposure for Vemurafenib)
Part 1: Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as Graded by National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg)
Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03
Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg)
Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Baseline up to 30 days from last dose of study drug (up to 117.8 months of treatment exposure for LGX818+MEK162 45 mg [combo 450]; up to 111.4 months of treatment exposure for LGX818 300 mg; up to 110.5 months of treatment exposure for Vemurafenib 960 mg)
+30 more secondary outcomes

Study Arms (4)

LGX818 450 mg + MEK162

EXPERIMENTAL

LGX818 450 mg QD + MEK162 45 mg BID

Drug: LGX818Drug: MEK162

Vemurafenib

ACTIVE COMPARATOR

Vemurafenib 960 mg BID

Drug: vemurafenib

LGX818 300 mg + MEK162

EXPERIMENTAL

LGX818 300 mg QD + MEK162 45 mg BID

Drug: LGX818Drug: MEK162

LGX818

EXPERIMENTAL

LGX818 300 mg QD

Drug: LGX818

Interventions

LGX818DRUG

LGX818- Orally 100 mg and 50 mg capsules

LGX818LGX818 300 mg + MEK162LGX818 450 mg + MEK162

MEK162DRUG

MEK162- Orally 15 mg tablets

LGX818 300 mg + MEK162LGX818 450 mg + MEK162

vemurafenibDRUG

Tablets in bottles or blisters 240 mg

Also known as: Zelboraf, PLX4032, RO5185426

Vemurafenib

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (282)

Retinal Consultants of Alabama P.C.

Birmingham, Alabama, 35233, United States

Location

UAB Callahan Eye Hospital

Birmingham, Alabama, 35233, United States

Location

UAB Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

UAB The Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35243, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Oncology Associates

Tucson, Arizona, 85710, United States

Location

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

Highlands Oncology Group

Rogers, Arkansas, 72758, United States

Location

Highlands Oncology Group - Fayetteville

Springdale, Arkansas, 72762, United States

Location

UC Irvine Medical Center

Orange, California, 92868, United States

Location

Rocky Mountain Cancer Centers (Williams) - USOR

Aurora, Colorado, 80012, United States

Location

Rocky Mountain Cancer Centers

Boulder, Colorado, 80303, United States

Location

Rocky Mountain Cancer Centers

Colorado Springs, Colorado, 80907, United States

Location

Rocky Mountain Cancer Centers (Williams) - USOR

Denver, Colorado, 80218, United States

Location

Rocky Mountain Cancer Centers

Lakewood, Colorado, 80228, United States

Location

Specialty Eye Care

Parker, Colorado, 80134, United States

Location

Rocky Mountain Cancer Centers

Pueblo, Colorado, 81008, United States

Location

University Cancer Institute

Boynton Beach, Florida, 33426, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Eye & Ear Infirmary- Opthalmology