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

February 9, 2026 updated by: Pfizer

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)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
921

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
    • Buenos Aires
      • CABA, Buenos Aires, Argentina, C1125ABD
        • Fundación CENIT para la Investigación en Neurociencias
    • Ciudad Autónoma de Buenosaires
      • Buenos Aires, Ciudad Autónoma de Buenosaires, Argentina, C1025ABI
        • Fundación Investigar
      • Buenos Aires, Ciudad Autónoma de Buenosaires, Argentina, C1426ANZ
        • Instituto Medico Especializado Alexander Fleming
  • Australia
    • New South Wales
      • Gateshead, New South Wales, Australia, 02290
        • Lake Macquarie Private Hospital
    • Queensland
      • Southport, Queensland, Australia, 4215
        • Tasman Oncology Research
      • Woolloongabba, Queensland, Australia, 4102
        • Princess Alexandra Hospital
    • South Australia
      • Woodville, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital
    • Victoria
      • Prahran, Victoria, Australia, 3004
        • The Alfred Hospital
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Sir Charles Gairdner Hospital
  • Brazil
      • Natal, Brazil, 59062-000
        • Liga Norte Riograndense Contra O Cancer
      • Rio de Janeiro, Brazil, 20220-410
        • Inca Instituto Nacional de Cancer
      • São Paulo, Brazil, 01321-001
        • Hospital BP Mirante
    • Estado de Bahia
      • Salvador, Estado de Bahia, Brazil, 41825-010
        • AMO - Assistência Multidisciplinar em Oncologia
    • Pernambuco
      • Recife, Pernambuco, Brazil, 50070-550
        • Instituto de Medicina Integral Professor Fernando Figueira
    • Rio Grande do Sul
      • Ijuí, Rio Grande do Sul, Brazil, 98700-000
        • Associacao Hospital de Caridade Ijui
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
        • Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784-400
        • Fundacao Pio XII
  • Canada
      • Québec, Canada, G1R 2J6
        • CHU de Quebec-Universite Laval - L' Hotel - Dieu de Quebec
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Sunnybrook Health Sciences Centre
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • McGill University Health Center
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l'Universite de Montreal
      • Montreal, Quebec, Canada, H2L 4M1
        • Centre Hospitalier De L'Universite De Montreal Hospital Notre Dame
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM Notrea Dame Hospital
  • Colombia
    • Bogota D.C.
      • Bogotá, Bogota D.C., Colombia, 110311
        • Hospital Universitario San Ignacio
  • Czechia
      • Olomouc, Czechia, 775 20
        • Fakultni nemocnice Olomouc
      • Prague, Czechia, 128 08
        • General Faculty Hospital
    • Moravskoslezský kraj
      • Ostrava, Moravskoslezský kraj, Czechia, 70852
        • Fakultni Nemocnice Ostrava
    • Praha, Hlavní Mesto
      • Prague, Praha, Hlavní Mesto, Czechia, 100 34
        • Fakultni nemocnice Kralovske Vinohrady
    • South Moravian
      • Brno, South Moravian, Czechia, 656 53
        • Mou/Mmci - Ppds
  • France
      • Bordeaux, France, 33075
        • Hopital Saint Andre Unite de Cancerologie Service de Dermatologie
      • Boulogne-Billancourt, France, 92104
        • Centre Hospitalier Universitaire Ambroise Pare
      • Nice, France, 06202
        • Groupe Hospitalier Archet I Et II
      • Paris, France, 75010
        • Hôpital Lariboisière
      • Paris, France, 75014
        • Institut Mutualiste Montsouris
      • Paris, France, 75475
        • Hopital Saint Louis
      • Paris, France, 75015
        • Ophtalmologist office
      • Pierre-Bénite, France, 69495
        • Hospices Civils de Lyon - Hôpital Lyon Sud
      • Reims, France, 51092
        • CHU de Reims - Hôpital Robert Debré
      • Strasbourg, France, 67091
        • Nouvel Hopital Civil
    • Isère
      • Grenoble, Isère, France, 38043
        • CHU de Grenoble
    • NORD
      • Lille, NORD, France, 59037
        • CHRU de Lille - Hôpital Huriet
    • Rhone
      • Lyon, Rhone, France, 69373
        • Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
    • Sarthe
      • Le Mans, Sarthe, France, 72037
        • Centre Hospitalier Le Mans
    • Val-de-marne
      • Villejuif, Val-de-marne, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Berlin, Germany, 10117
        • Charite-Universitaetsmedizin Berlin
      • Bonn, Germany, 53105
        • Universitatsklinikum Bonn
      • Dresden, Germany, 01309
        • Überörtliche Radiologische Gemeinschaftspraxis Dresden
      • Dresden, Germany, 01307
        • University Hospital Carl Gustav Carus at the Technical University of Dresden
      • Erfurt, Germany, 99089
        • Klinik fur Hautkrankheiten und Allergologie, Helios Hauttumorzentrum Erfurt, Helios Klinikum Erfurt
      • Essen, Germany, 45147
        • Universitatsklinikum Essen
      • Frankfurt am Main, Germany, 60590
        • Goethe-University Frankfurt/Main
      • Freiburg im Breisgau, Germany, 79106
        • Universitätsklinikum Freiburg, Klinik für Radiologie
      • Gera, Germany, 07548
        • SRH Wald-Klinikum Gera GmbH
      • Gera, Germany, 07548
        • Institut für Diagnostische und Interventionelle Radiologie
      • Gera, Germany, 75478
        • Klinik für Augenheilkunde
      • Hamburg, Germany, 20246
        • Universitätsklinik Hamburg Eppendorf
      • Hanover, Germany, 30159
        • Augenärzte am Kröpcke
      • Hanover, Germany, 30625
        • Medizinische Hochschule Hannover (Hannover Medical School)
      • Hanover, Germany, 30626
        • Institut für Diagnostische und Interventionelle Radilogie
      • Heidelberg, Germany, 69120
        • University Clinic Heidelberg - PPDS
      • Homburg, Germany, 66421
        • Universität des Saarlandes
      • Kiel, Germany, 24105
        • University Hospital Schleswig-Holstein, Campus Kiel
      • Mannheim, Germany, 68167
        • Augenklinik Universitätsklinikum Mannheim
      • Minden, Germany, 32427
        • Augen-Praxis_Minden
      • Münster, Germany, 48157
        • Fachklinik Hornheide Abteilung für Internistische Onkologie und Hämatologie
      • Nuremberg, Germany, 90419
        • Klinikum Nürnberg - Campus Nord
      • Regensburg, Germany, 93053
        • Klinik & Poliklinik für Augenheilkunde
      • Tübingen, Germany, 72076
        • Universitatsklinikum Tubingen
      • Ulm, Germany, 89081
        • Universitatsklinikum Ulm
      • Ulm, Germany, 89073
        • Internistische Schwerpunktpraxis Kardiologie Hämatologie Onkologie
    • Baden-Wurttemberg
      • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79104
        • Universitaetsklinikum Freiburg
      • Heidelberg, Baden-Wurttemberg, Germany, 69120
        • University Clinic Heidelberg - PPDS
      • Mannheim, Baden-Wurttemberg, Germany, 68135
        • Klinikum Mannheim Universitätsklinikum gGmbH
      • Tübingen, Baden-Wurttemberg, Germany, 72076
        • Universitatsklinikum Tubingen
      • Ulm, Baden-Wurttemberg, Germany, 89070
        • Universitatsklinikum Ulm
    • Bavaria
      • Bayreuth, Bavaria, Germany, 95445
        • Klinikum Bayreuth GmbH
      • München, Bavaria, Germany, 80337
        • LMU Klinikum
      • Nuremberg, Bavaria, Germany, 90419
        • Hautklinik, Klinikum Nürnberg, Universitätsklinik der Paracelsus Medizinischen Privatuniversität
      • Regensburg, Bavaria, Germany, 93053
        • Institut für Röntgendiagnostik
      • Regensburg, Bavaria, Germany, 93053
        • University Clinic Regensburg - PPDS
      • Würzburg, Bavaria, Germany, 97080
        • Universitatsklinikum Wurzburg
    • Hesse
      • Kassel, Hesse, Germany, 34125
        • Klinikum Kassel
    • Lower Saxony
      • Buxtehude, Lower Saxony, Germany, 21614
        • Augenarztzentrum Buxtehude
      • Buxtehude, Lower Saxony, Germany, 21614
        • Elben Klinken Stade ? Buxtehude
    • North Rhine-Westphalia
      • Bonn, North Rhine-Westphalia, Germany, 53127
        • Augenklinik Universitätsklinikum Bonn
      • Minden, North Rhine-Westphalia, Germany, 32429
        • Institut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin
      • Minden, North Rhine-Westphalia, Germany, 32429
        • Mühlenkreiskliniken - Johannes Wesling Klinikum Minden
    • Rhineland-Palatinate
      • Mainz, Rhineland-Palatinate, Germany, 55131
        • Universitätsmedizin der Johannes Gutenberg-Universität Mainz
    • Saxony
      • Leipzig, Saxony, Germany, 04103
        • Universitätsklinikum Leipzig AöR
    • Saxony-Anhalt
      • Magdeburg, Saxony-Anhalt, Germany, 39120
        • Universitätsklinikum Magdeburg A.ö.R.
    • Schleswig-Holstein
      • Lübeck, Schleswig-Holstein, Germany, 23538
        • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
  • Greece
      • Athens, Greece, 115 27
        • Laiko General Hospital of Athens
      • Neo Faliro, Greece, 185 47
        • Metropolitan Hospital
  • Hungary
      • Budapest, Hungary, H-1122
        • Orszagos Onkologiai Intezet
      • Budapest, Hungary, 01062
        • Magyar Honvedseg Egeszsegugyi Kozpont
      • Szolnok, Hungary, 05004
        • Jász-Nagykun-Szolnok Megyei Hetényi Géza Kórház-Rendelőintézet
    • Hajdú-Bihar
      • Debrecen, Hajdú-Bihar, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont
  • Israel
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus
      • Jerusalem, Israel, 91120
        • Hadassah Medical Center - PPDS
    • Tel Aviv
      • Ramat Gan, Tel Aviv, Israel, 5262100
        • Sheba Medical Center - PPDS
  • Italy
      • Bari, Italy, 70126
        • IRCCS Giovanni Paolo II Cancer Institute
      • Bergamo, Italy, 24127
        • ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
      • Genoa, Italy, 16132
        • IRCCS Az. Osp. Universitaria San Martino- IST
      • Milan, Italy, 20141
        • Istituto Europeo di Oncologia
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
      • Padua, Italy, 16132
        • Istituto Oncologico Veneto - I.R.C.C.S.
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo di Pavia
      • Ragusa, Italy, 97100
        • Azienda Ospedaliera Civile Maria Paternò Arezzo Ragusa
      • Ragusa, Italy, 97100
        • S. C. Oncologia Medica Presidio Ospedaliero Maria Paterno Arezzo
      • Rome, Italy, 00128
        • Policlinico Universitario Campus Biomedico
      • Siena, Italy, 53100
        • Azienza Ospedaliera Universitaria Senese
      • Udine, Italy, 33100
        • Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
    • Ancona
      • Torrette Site, Ancona, Italy, 60126
        • Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
    • Campania
      • Napoli, Campania, Italy, 80131
        • Azienda Ospedaliera Universitaria Federico II
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi
    • Lazio
      • Rome, Lazio, Italy, 00128
        • Policlinico Universitario Campus Biomedico Di Roma
      • Rome, Lazio, Italy, 00144
        • Istituto Nazionale Tumori Regina Elena
      • Rome, Lazio, Italy, 00167
        • Istituto Dermopatico dell'Immacolata IRCCS
      • Rome, Lazio, Italy, 128
        • Policlinico Universitario Campus Biomedico Di Roma
    • Lombardy
      • Brescia, Lombardy, Italy, 25123
        • ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia - INCIPIT - PIN
      • Lecco, Lombardy, Italy, 23900
        • Azienda Ospedaliera Ospedale Di Lecco
      • Milan, Lombardy, Italy, 20133
        • Istituto Nazionale dei Tumori
      • Milan, Lombardy, Italy, 20162
        • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda
      • Monza, Lombardy, Italy, 20900
        • Azienda Ospedaliera San Gerardo
    • Torino
      • Candiolo, Torino, Italy, 10060
        • Fondazione del Piemonte per l'Oncologia (IRCCS)
    • Tuscany
      • Pisa, Tuscany, Italy, 56126
        • Azienda Ospedaliero Universitaria Pisana
    • Umbria
      • Terni, Umbria, Italy, 05100
        • Azienda Ospedaliera Santa Maria di Terni
    • Veneto
      • Padua, Veneto, Italy, 35128
        • Clinica Oculistica
  • Japan
    • Fukuoka
      • Fukuoka, Fukuoka, Japan, 812-8582
        • Kyushu University Hospital
    • Nagano
      • Matsumoto, Nagano, Japan, 390-8621
        • Shinshu University Hospital
    • Niigata
      • Niigata, Niigata, Japan, 951-8566
        • Niigata Cancer Center Hospital
    • Tokyo
      • Chuo-ku, Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
    • Ôsaka
      • Osaka, Ôsaka, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital
  • Mexico
      • México, Mexico, 14050
        • Medica Sur, S. A. B de C. V. (Centro de Investigación Farmacológica y Biotecnológica CIF-BIOTEC)
    • Mexico City
      • Mexico City, Mexico City, Mexico, 14080
        • Instituto Nacional de Cancerologia
    • Nuevo León
      • Monterrey, Nuevo León, Mexico, 64460
        • Hospital Universitario Dr. Jose Eleuterio González
    • Quintana Roo
      • Cancún, Quintana Roo, Mexico, 77505
        • Cancun Oncology Center Galenia
  • Netherlands
      • Ariënsplein Enschede, Netherlands, 7513 JX
        • Medisch Spectrum Twente - Hospital
      • Enschede, Netherlands, 7512 KZ
        • Medisch Spectrum Twente
      • Groningen, Netherlands, 9713 GZ
        • Universitair Medisch Centrum Groningen
      • Heerlen, Netherlands, 6419 PC
        • Zuyderland Medisch Centrum - Heerlen
      • Leiden, Netherlands, 2300 RC
        • Leids Universitair Medisch Centrum
      • Maastricht, Netherlands, 6229 HX
        • Maastricht University Medical Center
      • Rotterdam, Netherlands, 3015 CE
        • Erasmus MC
      • Rotterdam, Netherlands, 3075 EA
        • Erasmus MC-Daniel den Hoed Oncologisch Centrum
    • Gelderland
      • Nijmegen, Gelderland, Netherlands, 6525 GA
        • Radboud University Nijmegen Medical Centre
    • North Brabant
      • Breda, North Brabant, Netherlands, 4818CK
        • Amphia Ziekenhuis
      • Eindhoven, North Brabant, Netherlands, 5631 BM
        • Maxima Medisch Centrum
    • North Holland
      • Amsterdam, North Holland, Netherlands, 1081 HV
        • VU Medisch Centrum
    • Overijssel
      • Enschede, Overijssel, Netherlands, 7513 ER
        • Medisch Spectrum Twente
      • Zwolle, Overijssel, Netherlands, 8025 AB
        • Isala Zwolle
    • Provincie Friesland
      • Leeuwarden, Provincie Friesland, Netherlands, 8934 AD
        • Medisch Centrum Leeuwarden
  • Norway
      • Oslo, Norway, 379
        • Oslo universitetssykehus HF, Utprøvingsenheten
      • Oslo, Norway, 379
        • Oslo Universitetssykehus HF
      • Oslo, Norway, NO-0424
        • Oslo Myeloma Center - PPDS
  • Poland
      • Warsaw, Poland, 00-001
        • Lux Med
    • Masovian Voivodeship
      • Warsaw, Masovian Voivodeship, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
      • Warsaw, Masovian Voivodeship, Poland, 01-673
        • Centrum Medyczne MAVIT Sp. z o.o.
  • Portugal
      • Lisbon, Portugal, 1099-023
        • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
      • Lisbon, Portugal, 1649-035
        • Centro Hospitalar de Lisboa Norte, E.P.E- Hospital de Santa Maria
      • Porto, Portugal, 4200-072
        • Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
    • Lisbon District
      • Lisbon, Lisbon District, Portugal, 1099-023
        • Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
    • Setúbal District
      • Almada, Setúbal District, Portugal, 2801-951
        • Hospital Garcia de Orta*E.P.E.
  • Russia
      • Moscow, Russia, 115478
        • Russian Oncology Research Center n a N N Blokhin
      • Ryazan, Russia, 390005
        • Ryazan Clinical Hospital n.a. Semashko
      • Ryazan, Russia, 390011
        • Ryazan Regional clinical oncology dispensary
      • Saint Petersburg, Russia, 197758
        • Scientific Research Institute of Oncology n.a. N.N. Petrov
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Centre Singapore
      • Singapore, Singapore, 169608
        • Singapore General Hospital (SGH)
      • Singapore, Singapore, 169610
        • Singapore National Eye Research Centre
      • Singapore, Singapore, 168583
        • National Cancer Centre - 30 Hospital Blvd
  • Slovakia
      • Bratislava, Slovakia, 833 10
        • Narodny onkologicky ustav - PPDS
      • Poprad, Slovakia, 058 01
        • POKO Poprad, s.r.o.
  • South Africa
      • Pretoria, South Africa, 00002
        • Steve Biko Academic Hospital
      • Pretoria, South Africa, 27
        • Mary Potter Oncology Centre
  • South Korea
      • Seoul, South Korea, 03722
        • Severance Hospital Yonsei University Health System - PPDS
    • Seoul Teugbyeolsi
      • Gangnam-gu, Seoul Teugbyeolsi, South Korea, 06351
        • Samsung Medical Center - PPDS
      • Seoul, Seoul Teugbyeolsi, South Korea, 05505
        • Asan Medical Center - PPDS
    • Seoul-teukbyeolsi [seoul]
      • Seoul, Seoul-teukbyeolsi [seoul], South Korea, 03080
        • Seoul National University Hospital
  • Spain
      • A Coruña, Spain, 15006
        • Hospital Universitario A Coruna
      • Alicante, Spain, 3010
        • Hospital General Universitario Dr. Balmis
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron - PPDS
      • Barcelona, Spain, 8036
        • Hospital Clinic de Barcelona
      • Barcelona, Spain, 8041
        • Hospital de la Santa Creu i Sant Pau
      • Barcelona, Spain, 08021
        • Centro de Oftalmologia Barraquer
      • Donostia / San Sebastian, Spain, 20014
        • Onkologikoa
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves
      • Lleida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova
      • Lleida, Spain, 25198
        • Hospital Arnau de Vilanova
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañon
      • Madrid, Spain, 28046
        • Hospital Universitario La Paz - PPDS
      • Málaga, Spain, 29011
        • Hospital Civil (Hospital Regional Universitario de Malaga)
      • Santa Cruz de Tenerife, Spain, 38010
        • Hospital Universitario Nuestra Sra de La Candelaria
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio - PPDS
      • Valencia, Spain, 46009
        • Fundación Instituto Valenciano de Oncología
    • Andalusia
      • Jerez de la Frontera, Andalusia, Spain, 11407
        • Hospital Universitario de Jerez
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
        • Hospital Universitario Germans Trias i Pujol
    • Catalonia
      • Barcelona, Catalonia, Spain, 08029
        • Cetir, Centre Mèdic, S.L
    • Madrid
      • Majadahonda, Madrid, Spain, 28220
        • Hospital Universitario Puerta de Hierro Majadahonda
    • Murcia
      • El Palmar, Murcia, Spain, 30120
        • Hospital Clinico Universitario Virgen de la Arrixaca
    • Navarre
      • Pamplona, Navarre, Spain, 31008
        • Clinica Universidad de Navarra
      • Pamplona, Navarre, Spain, 31008
        • Hospital Universitario de Navarra
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Spain, 33011
        • Hospital Universitario Central de Asturias
    • Sevilla
      • Seville, Sevilla, Spain, 41014
        • Hospital Nuestra Senora de Valme
  • Sweden
      • Gothenburg, Sweden, SE-41345
        • Sahlgrenska Universitetssjukhuset
      • Gävle, Sweden, SE-801 87
        • Gavle Sjukhus
      • Linköping, Sweden, 581 85
        • Universitetssjukhuset i Linköping
      • Lund, Sweden, 22221
        • Skånes Universitetssjukhus Lund
      • Solna, Sweden, 171 64
        • Karolinska Universitetssjukhuset Solna
      • Uppsala, Sweden, 751 85
        • Uppsala Universitet
  • Switzerland
      • Bern, Switzerland, 3010
        • Inselspital Bern
      • Zurich Flughafen, Switzerland, 8058
        • Universitatsspital Zurich
  • Turkey (Türkiye)
      • Ankara, Turkey (Türkiye), 6500
        • Gazi University Medical Faculty Gazi Hospital
      • Bornova, Turkey (Türkiye), 35100
        • Ege University Medical Faculty
      • Izmir, Turkey (Türkiye), 35100
        • Ege University Medical aculty
      • Izmir, Turkey (Türkiye), 35100
        • Sifa Universitesi Bornova Egitim Arastirma Hastanesi
  • United Kingdom
      • Broomfield, United Kingdom, CM1 7ET
        • Broomfield Hospital
      • Leeds, United Kingdom, LS9 7TF
        • St James University Hospital
      • London, United Kingdom, NW32QG
        • Royal Free Hospital
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust - PPDS
      • Oxford, United Kingdom, OX3 7LE
        • Churchill Hospital
      • Preston, United Kingdom, PR2 9HT
        • Royal Preston Hospital - NWCRN- PPDS
    • Cambridgeshire
      • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
        • Addenbrookes Hospital
    • Chelsea
      • London, Chelsea, United Kingdom, SW3 6JJ
        • The Royal Marsden NHS Foundation Trust
    • London, CITY of
      • Northwood, London, CITY of, United Kingdom, HA6 2RN
        • Mount Vernon Hospital
    • Surrey
      • Guildford, Surrey, United Kingdom, GU2 7XX
        • Royal Surrey County Hospital
    • Wirral
      • Bebington, Wirral, United Kingdom, CH63 4JY
        • The Clatterbridge Cancer Centre NHS Foundation Trust
    • YORK
      • Sheffield, YORK, United Kingdom, S10 2SJ
        • Weston Park Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
      • Birmingham, Alabama, United States, 35243
        • University of Alabama at Birmingham
      • Birmingham, Alabama, United States, 35233
        • Retinal Consultants of Alabama P.C.
      • Birmingham, Alabama, United States, 35233
        • UAB Callahan Eye Hospital
      • Birmingham, Alabama, United States, 35233
        • UAB Comprehensive Cancer Center
      • Birmingham, Alabama, United States, 35233
        • UAB The Kirklin Clinic
    • Arizona
      • Tucson, Arizona, United States, 85710
        • Arizona Oncology Associates
    • Arkansas
      • Fayetteville, Arkansas, United States, 72703
        • Highlands Oncology Group
      • Rogers, Arkansas, United States, 72758
        • Highlands Oncology Group
      • Springdale, Arkansas, United States, 72762
        • Highlands Oncology Group - Fayetteville
    • California
      • Orange, California, United States, 92868
        • UC Irvine Medical Center
    • Colorado
      • Aurora, Colorado, United States, 80012
        • Rocky Mountain Cancer Centers (Williams) - USOR
      • Boulder, Colorado, United States, 80303
        • Rocky Mountain Cancer Centers
      • Colorado Springs, Colorado, United States, 80907
        • Rocky Mountain Cancer Centers
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers (Williams) - USOR
      • Lakewood, Colorado, United States, 80228
        • Rocky Mountain Cancer Centers
      • Parker, Colorado, United States, 80134
        • Specialty Eye Care
      • Pueblo, Colorado, United States, 81008
        • Rocky Mountain Cancer Centers
    • Florida
      • Boynton Beach, Florida, United States, 33426
        • University Cancer Institute
      • Miami, Florida, United States, 33136
        • University of Miami
    • Illinois
      • Chicago, Illinois, United States, 60612
        • University of Illinois at Chicago
      • Chicago, Illinois, United States, 60612
        • University of Illinois Hospital and Health Sciences System
      • Chicago, Illinois, United States, 60612
        • University Of Illinois Medical Center
      • Chicago, Illinois, United States, 60612
        • Eye & Ear Infirmary- Opthalmology
      • Chicago, Illinois, United States, 60612
        • University of Illinois Hospital and Health Sciences System - Investigational Drug Service
      • Niles, Illinois, United States, 60714
        • Oncology Specialists, SC
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
    • Michigan
      • Grand Rapids, Michigan, United States, 49525
        • Retina Specialists Of Michigan
      • Grand Rapids, Michigan, United States, 49503
        • Lack's Cancer Center at Mercy Health Saint Mary's
      • Grand Rapids, Michigan, United States, 49503
        • Mercy Health Hauenstein Neuroscience Center Neuro-Ophthalmology (Clinic)
    • Mississippi
      • Hattiesburg, Mississippi, United States, 39401
        • Hattiesburg Clinic Oncology Hem
      • Jackson, Mississippi, United States, 39202
        • Jackson Oncology Associates - St. Dominic Hospital
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Nebraska Methodist Hospital
    • New Jersey
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
    • New York
      • Rochester, New York, United States, 14642
        • University of Rochester Medical Center - PPDS
      • Rochester, New York, United States, 14642
        • Investigational Drug Service, Department of Pharmacy (Investigational Product)
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74146
        • Tulsa Cancer Institute PLLC
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57104
        • Sanford Cancer Center Oncology Clinic & Pharmacy
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center Cancer Institute
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Baylor Charles A. Sammons Cancer Center
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center at Dallas
      • Dallas, Texas, United States, 75231
        • Dr. Dennis B. Kay (Ophthalmologist)
    • Vermont
      • Burlington, Vermont, United States, 05401
        • University of Vermont Medical Center
    • Virginia
      • Alexandria, Virginia, United States, 22304
        • Virginia Cancer Specialists, PC
      • Arlington, Virginia, United States, 22205
        • Virginia Cancer Specialists
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists (Leesburg) - USOR
      • Falls Church, Virginia, United States, 22044
        • Northern Virginia Ophthalmology Associates
      • Gainesville, Virginia, United States, 20155
        • Virginia Cancer Specialists, PC
    • Washington
      • Wenatchee, Washington, United States, 98801
        • Wenatchee Valley Hospital & Clinics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LGX818 450 mg + MEK162
LGX818 450 mg QD + MEK162 45 mg BID
Drug: LGX818
LGX818- Orally 100 mg and 50 mg capsules
Drug: MEK162
MEK162- Orally 15 mg tablets
Active Comparator: Vemurafenib
Vemurafenib 960 mg BID
Drug: vemurafenib
Tablets in bottles or blisters 240 mg
Other Names:
  • PLX4032
  • Zelboraf
  • RO5185426
Experimental: LGX818 300 mg + MEK162
LGX818 300 mg QD + MEK162 45 mg BID
Drug: LGX818
LGX818- Orally 100 mg and 50 mg capsules
Drug: MEK162
MEK162- Orally 15 mg tablets
Experimental: LGX818
LGX818 300 mg QD
Drug: LGX818
LGX818- Orally 100 mg and 50 mg capsules

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Progression Free Survival (PFS) by BIRC in Combo 450 Group as Compared to Vemurafenib Group
Time Frame: From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 29 months)
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
Time Frame: 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
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 1 and Part 2: Change From Baseline in EuroQoL-5 Dimension-5 Level (EQ-5D-5L) Index Score at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
EQ-5D-5L is a standardized participant completed questionnaire that measures health status in terms of a single index value or utility score. EQ-5D-5L consisted of two components: a health state profile (descriptive system) and a visual analogue scale (VAS) in which participants rate their overall health status from 0 (worst imaginable) to 100 (best imaginable), where higher scores indicated better health status. EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 response levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems and 5=extreme problems. EQ-5D-5L health status index score range between 0 to 1. Higher score indicated better health status.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/quality of life (QOL) scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represents more severe symptoms.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
Time Frame: Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead.
Part 1 and Part 2: Baseline, Day 1 of each cycle (Cycle 2 to Cycle 31)
Part 1: Plasma Concentrations of LGX 818
Time Frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Part 2: Plasma Concentrations of LGX 818
Time Frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8 hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Part 1: Plasma Concentrations of MEK162
Time Frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Part 2: Plasma Concentrations of MEK162
Time Frame: Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Cycle 1 Day 1: pre-dose, 0.5, 1.5, 4 to 8, hours post dose; Cycle 2 Day 1: pre-dose; Cycle 3 Day 1: pre-dose
Part 2: PFS by BIRC in Combo 300 Group as Compared to LGX818 Group
Time Frame: From randomization until documented PD, initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)
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 35 months)
Part 1: Overall Survival (OS)
Time Frame: 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)
Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death was not observed by the date of analysis cutoff, OS was censored at the date of last contact.
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
Time Frame: 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)
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or an important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms; Grade 2: moderate; Grade 3: severe/medically significant; Grade 4: life-threatening consequence; Grade 5: death. AEs and SAEs of all grades combined were reported.
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
Time Frame: 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)
Laboratory parameters were graded using NCI-CTCAE v4.03 where, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. Only categories with non-zero values for any reporting arm are reported.
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
Time Frame: 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)
Notably abnormal vital signs were: low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): <= 90 mmHg with decrease from baseline of >= 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high diastolic blood pressure (DBP) (mmHg): <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 beats per minute (bpm) with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight (kilogram): >=20 percent (%) decrease from baseline/>= 10% increase from baseline. Low/high body temperature degree Celsius (C): <= 36 degree C/>= 37.5 degree C. Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline.
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 Notable Electrocardiogram (ECG) Values
Time Frame: 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)
Newly occurring notable ECG values were reported for QT (millisecond [ms]), QT corrected interval using Fridericia's correction (QTcF) (ms), QT corrected interval using Bazett's correction formula (QTcB) (ms) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Criteria for newly occurring notable ECG values (QT, QTcF, QTcB) were New > 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60; heart rate: New <60, New >100.
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 Worst Post-Baseline Left Ventricular Ejection Fraction (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade
Time Frame: 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)
LVEF values were graded as Grade 0: non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
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 Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the NCI-CTCAE v4.03
Time Frame: 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)
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included severe cutaneous adverse reactions, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma, and melanomas. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AESIs of grade 3 or 4 are reported in this outcome measure.
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 Ocular-related AESI Graded According to the NCI-CTCAE v4.03
Time Frame: 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)
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Ocular related AESIs of grade 3 or 4 are reported in this outcome measure.
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 2: Percentage of Participants With AEs and SAEs as Graded by NCI-CTCAE, Version 4.03
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; resulted in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or an important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms; Grade 2: moderate; Grade 3: severe/medically significant; Grade 4: life-threatening consequence; Grade 5: death. AEs and SAEs of all grades combined were reported.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Laboratory parameters were graded using NCI-CTCAE v4.03 where, Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death. Clinically notable shift from baseline in laboratory parameter = worsening by at least 2 grades or to >=grade 3. Only categories with non-zero values for any reporting arm are reported.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Notably abnormal vital signs were: low/high SBP (mmHg): <= 90 mmHg with decrease from baseline of >= 20 mmHg/>= 160 mmHg with increase from baseline of >=20 mmHg. Low/high DBP (mmHg): <= 50 mmHg with decrease from baseline of >=15 mmHg/>=100 mmHg with increase from baseline of >=15 mmHg. Low/high Pulse rate: <=50 bpm with decrease from baseline of >=15 bpm/>= 120 bpm with increase from baseline of >=15 bpm. Low/high Weight (kilogram): >=20% decrease from baseline/>= 10% increase from baseline. Low/high body temperature degree C: <= 36 degree C/>= 37.5 degree C. Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Newly Occurring Notable ECG Values
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Criteria for newly occurring notable ECG values (QT, QTcF, QTcB) were New > 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60; heart rate: New <60, New >100.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Worst Post-baseline LVEF Values by MUGA Scans or Transthoracic ECHO, by CTCAE Grade
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
LVEF values were graded as Grade 0: non missing value below Grade 2; Grade 2: LVEF between 40% and 50% or absolute reduction from baseline >=10% and < 20%; Grade 3: LVEF between 20% and 39% or absolute reduction from baseline >=20%; Grade 4: LVEF lower than 20%. Baseline was defined as the last non-missing value prior to the first dose of study treatment. Missing data were due to participants who died or withdrew consent prior to the first scheduled evaluation or missed evaluations as protocol deviations.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Dermatologic-related AESI Graded According to the NCI-CTCAE v4.03
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included severe cutaneous adverse reactions, cutaneous non-squamous cell carcinoma, cutaneous squamous cell carcinoma and melanomas. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. AESIs of grade 3 or 4 are reported are reported in this outcome measure.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part 2: Number of Participants With Ocular-related AESI Graded According to the NCI-CTCAE v4.03
Time Frame: Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included uveitis-type events. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/ prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Ocular related AESIs of grade 3 or 4 are reported in this outcome measure.
Baseline up to 30 days after last dose of study drug (up to 106.3 M of treatment exposure for Part 2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for Part 2: LGX818 300 mg; up to 111.4 M of treatment exposure for Part 1+Part 2: LGX818 300 mg)
Part (P) 2: Overall Survival (OS)
Time Frame: From randomization until censoring date/death, whichever occurred 1st (up to 106.3 M of treatment exposure for P2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for P2: LGX818 300 mg; up to 111.4 M of treatment exposure for P1+P2: LGX818 300 mg)
OS was defined as the time from the date of randomization to the date of death due to any cause. If a death was not observed by the date of analysis cutoff, OS was censored at the date of last contact.
From randomization until censoring date/death, whichever occurred 1st (up to 106.3 M of treatment exposure for P2: LGX818+MEK162 45 mg; up to 98.4 M of treatment exposure for P2: LGX818 300 mg; up to 111.4 M of treatment exposure for P1+P2: LGX818 300 mg)
Part 1 and Part 2: Objective Response Rate (ORR)
Time Frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
ORR, calculated as the percentage of participants with a best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Results are reported for confirmed BIRC response. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure (OM).
From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Time to Objective Response (TTR)
Time Frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
TTR was the time between date of randomization until first documented response of CR or PR. Participants who did not achieve a PR or CR were censored at the last adequate tumor assessment date when they did not have a PFS event or at maximum follow-up (i.e. first patient first visit [FPFV] to last patient last visit [LPLV] used for the analysis) when they had a PFS event. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. TTR was estimated in the treatment arms using a Kaplan-Meier method. TTR was based on central review. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure.
From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Disease Control Rate (DCR)
Time Frame: From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
DCR was calculated as the percentage of participants with a best overall response (BOR) of CR, PR, or stable disease (SD). CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Two sets of DCR were considered, one for confirmed and one for unconfirmed responses. Results are reported for confirmed and unconfirmed responses combined. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. DCR was based on central review. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure.
From randomization until disease progression or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Duration of Response (DOR)
Time Frame: From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
DOR was calculated, as the time from the date of first documented response (CR or PR) to the first documented progression or death due to underlying cancer. DOR was estimated for responders (i.e. participants achieving at least once CR or PR) only using a Kaplan-Meier method. CR was defined as disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. If a participant with a CR or PR had no progression or death due to underlying disease, the participant was censored at the date of last adequate tumor assessment. Results are based on confirmed BIRC response. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure.
From randomization until disease progression, censoring date or death, whichever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
Time Frame: Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
FACT-M:melanoma specific questionnaire to assess participant health-related quality of life(QoL).Melanoma specific 16 subscale :signs,symptoms,physical/social activities most relevant to participants with advanced-stage melanoma.Other items :physical,functional and social/family well-being(7 items each),emotional well-being(6 items),surgery specific concerns related to melanoma(8 items,not included in this study).Each item range 0(not at all)to 4(very much),combined to produce subscale scores.Total score range for FACT-M excluding surgery specific items is 0 to172,higher scores:better QoL.Melanoma subscale score range from0(worst)to 64(best response),higher score:better QoL.Time to definitive 10% deterioration:time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause.All collected data up to pre-specified collection period(i.e.,end of study)are reported for this OM.
Date of randomization to date of event or death due to any cause, which ever occurred first (up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Global Health Status Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Time Frame: Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
EORTC QLQ-C30 is 30 item questionnaire composed of 5 multi-item functional subscales (physical,role,cognitive,emotional,social functioning), 3 multi-item symptom scales (fatigue,nausea/vomiting, and pain),global health/quality of life (QOL) subscale and 6 single items assessing other cancer related symptoms (dyspnea,sleep disturbance, appetite, diarrhea, constipation and financial impact of cancer). It employed twenty-eight 4 point Likert scales with responses from "not at all" to "very much" and two 7 point Likert scales for global health and overall QOL. Global health status scale score ranged from 0 to 100. Higher score: better level of functioning. Time to definitive 10% deterioration: time from date of randomization to date of event with at least 10% relative to baseline worsening of corresponding scale score with no later improvement or death due to any cause. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure.
Date of randomization to date of event or death due to any cause, which ever occurred first (maximum up to 29 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 35 months for Part 2 and Part 1 LGX 300 mg group)
Part 1 and Part 2: Change From Baseline in the FACT-M Subscale at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
FACT-M: melanoma specific questionnaire to assess participant health-related quality of life. Melanoma specific subscale consists of 16 items related to signs, symptoms, physical/social activities most relevant to participants with advanced-stage melanoma. Other items include physical, functional and social/family well-being (7 items each), emotional well-being (6 items), surgery specific concerns related to melanoma (8 items, not included in this study). Each item ranged from 0 (not at all) to 4 (very much), combined to produce subscale scores. Total score range for FACT-M excluding surgery specific items is 0 to 172, higher scores represented better quality of life. Melanoma subscale score ranged from 0 (worst response) to 64 (best response), higher score indicated better quality of life.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Change From Baseline in Emotional Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/ QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represent a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Change From Baseline in Physical Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Change From Baseline in Social Functioning Scale Score of the EORTC QLQ-C30 at Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and End of Treatment Visit
Time Frame: Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
EORTC QLQ-C30 contains 30 items and is composed of multi-item and single-item measures. These include 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/QOL scale. The questionnaire employs 28 4-point Likert scales with responses from "not at all" to "very much" and two 7-point Likert scales for global health and overall QOL. Responses to all items converted to 0 to 100 scale. For functional and global QOL scales, higher scores represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.
Baseline (Day 1 of Cycle 1), Day 1 of Cycle 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25 and end of treatment visit (within14 days after the last dose of study drug)
Part 1 and Part 2: Time to Definitive 1 Point Deterioration in ECOG PS
Time Frame: Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)
ECOG: participant's performance status was measured on a 6-point scale: 0= fully active/able to carry on all pre-disease activities without restriction; 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light and sedentary nature; 2= ambulatory and capable of all self-care, but unable to carry out any work activities, up and about more than 50% of waking hours; 3= capable of only limited self-care, confined to bed/chair >50% of waking hours; 4= completely disabled, cannot carry on any self-care, totally confined to bed/chair: 5= dead. Definitive deterioration was defined as death due to any cause or decrease in ECOG PS by at least one category from baseline score with no subsequent improvement. All collected data up to the pre-specified collection period (i.e., end of study) are reported for this outcome measure.
Baseline up to 30 days from last dose of study drug (up to 30 months for Part 1, excluding Part 1: LGX818 300 mg group; up to 36 months for Part 2 and Part 1 LGX 300 mg group)

Collaborators and Investigators

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Sponsor

Sponsor

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Pfizer

Investigators

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  • Study Director: Pfizer CT.gov Call Center, Pfizer

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General Publications

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Study Start (Actual)

Study Start

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September 12, 2013

Primary Completion (Actual)

Primary Completion

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November 9, 2016

Study Completion (Actual)

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September 3, 2024

Study Registration Dates

First Submitted

First Submitted

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July 24, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

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July 24, 2013

First Posted (Estimated)

First Posted

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July 26, 2013

Study Record Updates

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February 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

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February 9, 2026

Last Verified

Last Verified

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February 1, 2026

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Other Study ID Numbers

Other Study ID Numbers

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  • CMEK162B2301
  • C4221004 (Other Identifier: Alias Study Number)
  • 2013-001176-38 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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