Back to results

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

Primary Purpose

Melanoma

Status

Active

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

LGX818

MEK162

vemurafenib

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Melanoma, Cutaneous melanoma, Skin disease, Skin cancer, Skin Neoplasms, Neoplasm Metastasis, BRAF mutant, BRAF V600E, BRAF V600K, Cancer, LGX818, MEK162, vemurafenib, combination, BRAF inhibitor, resistance, The combination of a selective BRAF- and a MEK1/2-inhibitor, Prior immunotherapy, MEK inhibitor, Phase III, Combo 300, Combo 450

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

UAB Comprehensive Cancer Center
Retinal Consultants of Alabama P.C.
UAB Callahan Eye Hospital
UAB Comprehensive Cancer Center
University of Alabama at Birmingham
University of Alabama at Birmingham
Highlands Oncology Group
Highlands Oncology Group
UC Irvine Medical Center
UC Irvine Medical Center
Rocky Mountain Cancer Centers (Williams) - USOR
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers
Rocky Mountain Cancer Centers (Williams) - USOR
Rocky Mountain Cancer Centers
Specialty Eye Care
Rocky Mountain Cancer Centers
University of Illinois at Chicago
University of Illinois Hospital and Health Sciences System - Investigational Drug Service
Eye & Ear Infirmary- Opthalmology
University of Illinois Hospital and Health Sciences System
University of Illinois Medical Center
Goshen Center For Cancer Care
Lack's Cancer Center at Mercy Health Saint Mary's
Mercy Health Hauenstein Neuroscience Center Neuro-Ophthalmology (Clinic)
Retina Specialists of Michigan
Jackson Oncology Associates - St. Dominic Hospital
Jackson Oncology Associates - St. Dominic Hospital
Jackson Oncology Associates, PLLC
Hackensack University Medical Center
Hackensack University Medical Center
Investigational Drug Service, Department of Pharmacy (Investigational Product)
University of Rochester Medical Center - PPDS
Dr. Dennis B. Kay (Ophthalmologist)
Texas Oncology - Baylor Charles A. Sammons Cancer Center
University of Vermont Medical Center
University of Vermont Medical Center
University of Vermont Cancer Center
Virginia Cancer Specialists, PC
Virginia Cancer Specialists
Virginia Cancer Specialists (Leesburg) - USOR
Virginia Cancer Specialists, PC
Virginia Cancer Specialists
Northern Virginia Ophthalmology Associates
Northern Virginia Ophthalmology Associates
Virginia Cancer Specialists, PC
Virginia Cancer Specialists (Leesburg) - USOR
Virginia Cancer Specialists, PC
Wenatchee Valley Hospitals & Clinics
Wenatchee Valley Medical Center
Fundación CENIT para la Investigación en Neurociencias
Organización Médica de Investigación
Fundación Investigar
Sanatorio de La Providencia
Hospital Italiano de Buenos Aires
Instituto Médico Especializado Alexander Fleming
Centro de Diagnóstico Dr. Enrique Rossi
Lake Macquarie Private Hospital
HPS Pharmacy
Tasman Oncology Research
Vision Optical
Princess Alexandra Hospital
The Alfred Hospital
The Alfred Hospital
Sir Charles Gairdner Hospital Pharmacy Department
Sir Charles Gairdner Hospital
Instituto de Medicina Integral Professor Fernando Figueira
Associação Hospital de Caridade Ijuí
Hospital de Clinicas de Porto Alegre (HCPA) - PPDS
Fundação PIO XII
Liga Norte Riograndense Contra O Cancer
INCA Instituto Nacional de Cancer
Hospital BP Mirante
Tom Baker Cancer Centre
SunnyBrook Health Sciences Centre
Sunnybrook Research Institute
Toronto General Hospital
Princess Margaret Cancer Centre
Centre Hospitalier De L'Universite De Montreal Hospital Notre Dame
CHUM Notrea Dame Hospital
Centre Hospitalier de l'Universite de Montreal
McGill University Health center
CHU de Quebec-Universite Laval
CHU de Quebec- L'Hotel-Dieu de Quebec
Centre de Sante Et Services Sociaux Richelieu Yamaska
Centre Hospitalier Universitaire de Quebec - Hotel - Dieu de Quebec - Universite Laval
Hospital Universitario San Ignacio
Hospital Universitario San Ignacio
Mou/Mmci - Ppds
Fakultni nemocnice Ostrava
Fakultni nemocnice Kralovske Vinohrady
Vseobecna Fakultni Nemocnice V Praze
Fakultni nemocnice u sv. Anny v Brne
Fakultni nemocnice Olomouc
Fakultni nemocnice Ostrava
CHU de Nice
Hôpital Saint-André
CHU de Grenoble
Hôpital Robert Debré
CHRU de Lille - Hôpital Huriet
Centre Léon Bérard Centre Régional de Lutte Contre Le Cancer Rhône Alpes
Hôpital de La Croix Rousse
Centre Hospitalier Le Mans
Institut Gustave Roussy
Centre Hospitalier Universitaire Ambroise Paré
Clinique de la Louvière
Hôpital D'Instruction des Armées Desgenettes
Groupe Hospitalier Archet I Et II
Hopital Lariboisiere
Institut Mutualiste Montsouris
Ophtalmologist office
Hôpital Saint louis
Service de PneumologieCHU Lyon Sud
Nouvel Hopital Civil
Cardiologist Private Practice
Institut Gustave Roussy
Universitaetsklinikum Freiburg
University Clinic Heidelberg - PPDS
Klinikum Mannheim Universitätsklinikum gGmbH
Universitätsklinikum Tübingen
Universitätsklinikum Ulm
Hautklinik, Klinikum Nürnberg, Universitätsklinik der Paracelsus Medizinischen Privatuniversität
LMU Klinikum der Universität München
LMU Klinikum
Institut für Röntgendiagnostik
University Clinic Regensburg - PPDS
Universitätsklinikum Würzburg
Universitätsklinikum Frankfurt
Klinikum Kassel
Zentrum für Radiologie
Augenarztzentrum Buxtehude
Elben Klinken Stade ? Buxtehude
Augenklinik Universitätsklinikum Bonn
Institut für Diagnostische Radiologie, Neuroradiologie und Nuklearmedizin
Johannes Wesling Klinikum Minden
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Universitätsklinik Magdeburg
Klinik und Poliklinik für Augenheilkunde
Universitatsklinikum Leipzig AoR
Universitatsklinikum Leipzig
Universitatsklinikum Schleswig-Holstein
Universitatsklinikum Schleswig-Holstein - Kiel
Charite-Universitaetsmedizin Berlin
Universitätsklinikum Bonn
Universitätsklinikum Bonn
University Hospital Carl Gustav Carus Dersden
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Überörtliche Radiologische Gemeinschaftspraxis Dresden
Diagnostische und interventionelle Radiologie und Neuroradiologie
Helios Klinikum Erfurt
Universitätsklinikum Essen
Universitätsklinikum Freiburg, Klinik für Radiologie
Institut für Diagnostische und Interventionelle Radiologie
SRH Wald-Klinikum Gera GmbH
Klinik für Augenheilkunde
Universitätsklinik Hamburg Eppendorf
Augenärzte am Kröpcke
Medizinische Hochschule Hannover (Hannover Medical School)
Institut für Diagnostische und Interventionelle Radilogie
University Clinic Heidelberg - PPDS
Universität des Saarlandes
Universitatsklinikum Schleswig-Holstein - Kiel
Universitatsklinikum Schleswig-Holstein
Universitatsklinikum Schleswig-Holstein
Universitätsaugenklinik
Universitätsklinik für Radiologie und Nuklearmedizin
University Hospital Mainz
Augenklinik Universitätsklinikum Mannheim
Augen-Praxis_Minden
LMU Klinikum der Universität
Hautklinik, Klinikum Nürnberg, Universitätsklinik der Paracelsus Medizinischen Privatuniversität
Fachklinik Hornheide Abteilung für Internistische Onkologie und Hämatologie
Klinik & Poliklinik für Augenheilkunde
Universitätsklinikum Tübingen
Internistische Schwerpunktpraxis Kardiologie Hämatologie Onkologie
Universitätsklinikum Ulm
Hygeia Diagnostic and Therapeutic Centre of Athens
Laiko General Hospital of Athens
Laiko General Hospital of Athens
Metropolitan Hospital
Debreceni Egyetem Klinikai Kozpont
Magyar Honvédség Egészségügyi Központ
Orszagos Onkologiai Intezet
Debreceni Egyetem Klinikai Kozpont
Jasz-Nagykun-Szolnok Megyei Hetenyi Geza Korhaz-Rendelointezet
Rambam Health Care Campus
Rambam Health Care Campus
Sheba Medical Center - PPDS
Rambam Health Care Campus
Hadassah Medical Center - PPDS
Rambam Health Care Campus
Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
Azienda Ospedaliera Universitaria Federico II
Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi-Via Massarenti
Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi
Policlinico Universitario Campus Biomedico Di Roma
Istituto Nazionale Tumori Regina Elena
Azienda Ospedaliera Sant'Andrea
Policlinico Universitario Campus Biomedico Di Roma
Azienda Ospedaliera Ospedale Di Lecco
Istituto Europeo Di Oncologia
ASST di Monza - Azienda Ospedaliera San Gerardo
Azienda Ospedaliera San Gerardo
Istituto Clinico Humanitas - Humanitas Cancer Center
Istituto Clinico Humanitas
Fondazione del Piemonte per l'Oncologia (IRCCS)
Azienda Ospedaliero Universitaria Pisana
Azienda Ospedaliera S Maria Di Terni
Clinica Oculistica
IRCCS Giovanni Paolo II Cancer Institute
ASST Papa Giovanni XXIII - Azienda Ospedaliera Papa Giovanni XXIII
Azienda Ospedaliero Universitaria Di Bologna - Policlinico S.Orsola Malpighi
IRCCS Az. Osp. Universitaria San Martino- IST
Istituto Europeo Di Oncologia
Istituto Nazionale per lo studio e la cura dei tumori Fondazione Giovanni Pascale
Istituto Oncologico Veneto - I.R.C.C.S.
Fondazione IRCCS Policlinico San Matteo di Pavia
Azienda Ospedaliera Civile Maria Paternò Arezzo Ragusa
Policlinico Universitario Campus Biomedico
Azienza Ospedaliera Universitaria Senese
Ospedale Koelliker
Azienda Sanitaria Universitaria Integrata di Udine - PO Universitario Santa Maria della Misericordia
Kyushu University Hospital
Shinshu University Hospital
Niigata Cancer Center Hospital
Niigata Cancer Center Hospital
National Cancer Center Hospital
Niigata Cancer Center Hospital
National Hospital Organization Osaka National Hospital
Samsung Medical Center - PPDS
Asan Medical Center - PPDS
Seoul National University Hospital
Seoul National University Hospital
Severance Hospital Yonsei University Health System - PPDS
Asan Medical Center - PPDS
Samsung Medical Center - PPDS
Seoul National University Hospital
Severance Hospital Yonsei University Health System - PPDS
Samsung Medical Center - PPDS
Instituto Nacional de Cancerologia
Medica Sur, S. A. B de C. V. (Centro de Investigación Farmacológica y Biotecnológica CIF-BIOTEC)
Instituto Nacional de Cardiología Ignacio Chavez
Radboud University Nijmegen Medical Centre
Zuyderland Medisch Centrum
VU Medisch Centrum
Amphia Ziekenhuis
Amphia Ziekenhuis
Maxima Medisch Centrum
Maxima Medisch Centrum
Medisch Spectrum Twente
Isala Klinieken
Universitair Medisch Centrum Groningen
Leids Universitair Medisch Centrum
Maastricht University Medical Center
Erasmus MC
Erasmus MC-Daniel den Hoed Oncologisch Centrum
Zuyerland Medisch Centrum
Oslo universitetssykehus HF, Utprøvingsenheten
Oslo universitetssykehus HF
Oslo Myeloma Center - PPDS
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
Centrum Medyczne MAVIT Sp. z o.o.
Lux Med
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
Hospital Garcia de Orta*E.P.E.
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.
Centro Hospitalar de Lisboa Norte E.P.E - Hospital Pulido Valente - PPDS
Hospital de Santa Maria-Avenida Prof. Egas Moniz - PPDS
Hospital de Santa Maria
Instituto Portugues de Oncologia Do Porto Francisco Gentil Epe - PPDS
Russian Oncology Research Center n a N N Blokhin
Ryazan Regional Clinical Oncology Dispensary
Ryazan Clinical Hospital n.a. Semashko
Ryazan Regional Clinical Oncology Dispensary
Scientific Research Institute of Oncology n.a. N.N. Petrov
Singapore General Hospital (SGH)
National Cancer Centre - 30 Hospital Blvd
National Cancer Centre Singapore
Singapore National Eye Research Centre
Nemocnica Svateho Michala, a.s.
Narodny onkologicky ustav - PPDS
Narodny onkologicky ustav Bratislava
BIONT, a.s.
POKO POPRAD, s.r.o.
Steve Biko Academic Hospital
Mary Potter Oncology Centre
Hospital de Jerez
Hospital Universitario Central de Asturias
Hospital Universitario Germans Trias i Pujol
Cetir, Centre Mèdic, S.L
Hospital Universitario Puerta de Hierro Majadahonda
Hospital Universitario Puerta de Hierro - Majadahonda
Hospital Universitario Virgen De La Arrixaca
Clinica Universidad Navarra
Complejo Hospitalario de Navarra
Hospital Nuestra Señora de Valme
Hospital General Universitario de Alicante
Hospital General Universitario Dr. Balmis
Hospital Universitario Germans Trias i Pujol
Centro de Oftalmologia Barraquer
Hospital Universitario Vall d'Hebron - PPDS
Hospital Clinic de Barcelona
Hospital Clinic provincial de Barcelona
Hospital de La Santa Creu i Sant Pau
Hospital Clinic de Barcelona
Hospital de La Santa Creu i Sant Pau
Onkologikoa
Hospital Universitario Virgen de las Nieves
Hospital Universitario A Coruña
Hospital Arnau de Vilanova
Hospital Universitari Arnau de Vilanova
Hospital General Universitario Gregorio Maranon
Hospital Universitario 12 de Octubre
Hospital Universitario Ramon y Cajal
Hospital Universitario 12 de Octubre
Hospital Universitario Puerta de Hierro - Majadahonda
Hospital Regional Universitario de Malaga ? Hospital General
Hospital Universitario Virgen del Rocio - PPDS
Fundacion Instituto Valenciano de Oncologia
Gävle Sjukhus
Sahlgrenska Universitetssjukhuset
Skanes Universitetssjukhus Lund
Karolinska Universitetssjukhuset Solna
Uppsala Universitet
Universitätsspital Zürich
Inselspital Bern
Dr. med. Nicole Gasser
Dr.med. Ursula Urner
Institut für diagnostische und interventionelle Radiologie
Ege University Medical Faculty
Ege University Medical aculty
Sifa Universitesi Bornova Egitim Arastirma Hastanesi
Addenbrookes Hospital
Mid Essex Hospital Services NHS Trust
The Royal Marsden NHS Foundation Trust
Royal Preston Hospital
Royal Marsden Hospital - Surrey
The Royal Marsden in Sutton, Surrey - Downs Rd
Royal Surrey County Hospital
Clatterbridge Hospital - PPDS
Clatterbridge Hospital
Weston Park Hospital
Broomfield Hospital
Cambridge University Hospitals NHS Foundation Trust
St James University Hospital
Royal Free Hospital
The Christie NHS Foundation Trust - PPDS
Churchill Hospital
Churchill Hospital
Royal Preston Hospital - PPDS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

LGX818 450 mg + MEK162

Vemurafenib

LGX818 300 mg + MEK162

LGX818

Arm Description

LGX818 450 mg QD + MEK162 45 mg BID

Vemurafenib 960 mg BID

LGX818 300 mg QD + MEK162 45 mg BID

LGX818 300 mg QD

Outcomes

Primary Outcome Measures

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (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).

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (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 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 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.

Secondary Outcome Measures

Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 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 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.

Part 1: Overall Survival (OS)

Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a death had not been observed by the date of analysis cutoff, OS was censored at the date of last contact.

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

AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that results in death; is life-threatening; requires inpatient hospitalization/prolongation of existing hospitalization; results in persistent/significant disability/incapacity; results in congenital anomaly/birth defect or that is considered to be important medical event. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (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; Grade 5: death. AEs of all grades were reported.

Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.03 were graded from Grades 1 to 5. 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.

Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) (millimeter of mercury [mmHg]): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 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.

Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values

Newly occurring notable ECG values were reported for QT (millisecond [ms]), QTcF (millisecond), QTcB (millisecond) and heart rate (beats per minute). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New greater than (>) 450, New >480, New >500, Increase from baseline >30, Increase from baseline >60. Heart rate: New <60, New >100 was considered as newly occurring notable value.

Part 1: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline 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.

Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and Palmar-plantar erythrodysaesthesia (PPE) syndrome. 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. AEs of grade 3 or 4 are reported in this outcome measure.

Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding retinal vein occlusion (RVO), RVO and 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. AEs of grade 3 or 4 are reported in this outcome measure.

Part 2: 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

Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.0

Number of participants with clinically notable shift from baseline in laboratory parameter values based on national cancer institute common terminology criteria (NCI-CTCAE) grade, Version 4.0 were graded from Grades 1 to 5. 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.

Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Notably abnormal vital signs were: Low/high systolic blood pressure (SBP) in millimeter of mercury (mmHg): less than or equal to (<=) 90 mmHg with decrease from baseline of greater than or equal to (>=) 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 [bpm]: <=50 bpm with decrease from baseline of >=15 bpm/>=120 bpm with increase from baseline of >=15 bpm, Low/high weight (kg): >=20 % decrease from baseline/>= 10% increase from baseline Low/high Body temperature degree C): <= 36°C/>= 37.5 degree C.

Part 2: Number of Participants With Newly Occurring Notable ECG Values

Newly occurring notable ECG values were reported for QT (ms), QTcF (ms), QTcB (ms) and heart rate (bpm). Newly occurring was defined as participants not meeting criterion at baseline and meeting criterion post-baseline. Ranges for newly occurring notable ECG values (QT, QTcF, QTcB) are New >450, New >480, New >500, increase from baseline >30, Increase from baseline >60. Heart rate: New < 60, New >100 was considered as newly occurring notable value.

Part 2: Number of Participants With Worst Post-baseline Left Ventricular Dysfunction Events (LVEF) Values by Multigated Acquisition (MUGA) Scans or Transthoracic Echocardiograms (ECHO), by CTCAE Grade

Participants with worst post-baseline 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.

Part 2: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Dermatologic-related AESI included rash, photosensitivity, nail disorders, skin infections, severe cutaneous adverse reactions and PPE syndrome. 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. AEs of grade 3 or 4 are reported are reported in this outcome measure.

Part 2: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

AESI consisted of events for which there was a specific clinical interest with regard to LGX818 and/or MEK162 treatment. Ocular-related AESI included retinopathy excluding RVO, RVO and 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. AEs of grade 3 or 4 are reported in this outcome measure.

Part 2: Overall Survival (OS)

Part 1 and Part 2: Objective Response Rate (ORR)

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.

Part 1 and Part 2: Time to Objective Response (TTR)

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.

Part 1 and Part 2: Disease Control Rate (DCR)

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.

Part 1 and Part 2: Duration of Response (DOR)

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.

Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale

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 range 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 represent better quality of life.Melanoma subscale score range from 0(worst response) to 64(best response),higher score indicated better quality of life. 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.

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)

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 represented 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.

Part 1 and Part 2: Change From Baseline in the Function Assessment Cancer Therapy-melanoma (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

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 range 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 range from 0(worst response) to 64(best response),higher score indicated better quality of life.

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

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.

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

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.

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

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

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 represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.

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

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 represented a better level of functioning/QOL. For symptom-oriented scales, a higher score represented more severe symptoms.

Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

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: Plasma Concentrations of LGX 818

Part 2: Plasma Concentrations of LGX 818

Part 1: Plasma Concentrations of MEK162

Part 2: Plasma Concentrations of MEK162

Part 1 and Part 2: Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group Performance Status (ECOG PS)

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 percent (%) 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.

Full Information

NCT ID

NCT01909453

First Posted

July 24, 2013

Last Updated

September 6, 2023

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT01909453

Brief Title

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

Acronym

COLUMBUS

Official Title

A 2-part Phase III Randomized, Open Label, Multicenter Study of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 13, 2013 (Actual)

Primary Completion Date

November 9, 2016 (Actual)

Study Completion Date

November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: LGX818 450 mg QD plus MEK162 45 mg BID (denoted as Combo 450 arm) LGX818 300 mg QD monotherapy (denoted as LGX818 arm) or 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: LGX818 300 mg QD plus MEK162 45 mg BID (denoted as Combo 300 arm) or LGX818 300 mg QD monotherapy (denoted as LGX818 arm)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

Melanoma, Cutaneous melanoma, Skin disease, Skin cancer, Skin Neoplasms, Neoplasm Metastasis, BRAF mutant, BRAF V600E, BRAF V600K, Cancer, LGX818, MEK162, vemurafenib, combination, BRAF inhibitor, resistance, The combination of a selective BRAF- and a MEK1/2-inhibitor, Prior immunotherapy, MEK inhibitor, Phase III, Combo 300, Combo 450

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

921 (Actual)

8. Arms, Groups, and Interventions

Arm Title

LGX818 450 mg + MEK162

Arm Type

Experimental

Arm Description

LGX818 450 mg QD + MEK162 45 mg BID

Arm Title

Vemurafenib

Arm Type

Active Comparator

Arm Description

Vemurafenib 960 mg BID

Arm Title

LGX818 300 mg + MEK162

Arm Type

Experimental

Arm Description

LGX818 300 mg QD + MEK162 45 mg BID

Arm Title

LGX818

Arm Type

Experimental

Arm Description

LGX818 300 mg QD

Intervention Type

Drug

Intervention Name(s)

LGX818

Intervention Description

LGX818- Orally 100 mg and 50 mg capsules

Intervention Type

Drug

Intervention Name(s)

MEK162

Intervention Description

MEK162- Orally 15 mg tablets

Intervention Type

Drug

Intervention Name(s)

vemurafenib

Other Intervention Name(s)

Zelboraf, PLX4032, RO5185426

Intervention Description

Tablets in bottles or blisters 240 mg

Primary Outcome Measure Information:

Title

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to Vemurafenib Group

Description

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)

Title

Part 1: Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) in Combo 450 Group as Compared to LGX818 Group

Description

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 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.

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), excluding Part 1: LGX818 300 mg group; up to 35 months for Part 1: LGX 300 mg group

Secondary Outcome Measure Information:

Title

Part 2: Progression Free Survival (PFS) by BIRC in Combo 300 Group as Compared to LGX818 Group

Description

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 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.

Time Frame

From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 35 months)

Title

Part 1: Overall Survival (OS)

Description

Time Frame

From randomization until documented disease progression (PD), initiation of new anti-cancer therapy, censoring date or death, whichever occurred first (up to 38 months)

Title

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

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Part 1: Number of Participants With Ocular-related Adverse Events of Special Interest (AESI) Graded According to the National Cancer Institute Common Terminology Criteria (NCI-CTCAE) v4.03

Description

Time Frame

Baseline up to 30 days from last dose of study drug (up to 30 months), excluding Part 1: LGX818 300 mg group; up to 36 months for Part 1 LGX 300 mg group

Title

Part 2: 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

Description

Time Frame