TriangleNCT01909453 · CITED IN SOURCE DOCUMENTS
Study Comparing Combination of LGX818 Plus MEK162 Versus Vemurafenib and LGX818 Monotherapy in BRAF Mutant Melanoma
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2026-02-27
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)
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Part 1: Progression Free Survival (PFS) by BIRC in Combo 450 Group as Compared to Vemurafenib Group
Part 1: PFS by BIRC in Combo 450 Group as Compared to LGX818 Group
Part 2: PFS by BIRC in Combo 300 Group as Compared to LGX818 Group
Part 1: Overall Survival (OS)
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
Part 1: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03
Part 1: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Part 1: Number of Participants With Newly Occurring Notable Electrocardiogram (ECG) Values
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
Part 1: Number of Participants With Dermatologic-related Adverse Events of Special Interest (AESI) Graded According to the NCI-CTCAE v4.03
Part 1: Number of Participants With Ocular-related AESI Graded According to the NCI-CTCAE v4.03
Part 2: Percentage of Participants With AEs and SAEs as Graded by NCI-CTCAE, Version 4.03
Part 2: Number of Participants With Clinically Notable Shift From Baseline in Laboratory Parameter Values Based on NCI-CTCAE Grade, Version 4.03
Part 2: Number of Participants With Newly Occurring Notably Abnormal Vital Signs
Part 2: Number of Participants With Newly Occurring Notable ECG Values
Part 2: Number of Participants With Worst Post-baseline LVEF Values by MUGA Scans or Transthoracic ECHO, by CTCAE Grade
Part 2: Number of Participants With Dermatologic-related AESI Graded According to the NCI-CTCAE v4.03
Part 2: Number of Participants With Ocular-related AESI Graded According to the NCI-CTCAE v4.03
Part (P) 2: Overall Survival (OS)
Part 1 and Part 2: Objective Response Rate (ORR)
Part 1 and Part 2: Time to Objective Response (TTR)
Part 1 and Part 2: Disease Control Rate (DCR)
Part 1 and Part 2: Duration of Response (DOR)
Part 1 and Part 2: Time to Definitive 10% Deterioration in the Function Assessment Cancer Therapy-melanoma (FACT-M) Subscale
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)
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
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
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
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
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
Part 1 and Part 2: Number of Participants With Change From Baseline in Eastern Cooperative Oncology Group Performance Status (ECOG PS)
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 ECOG PS
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- LGX818 450 mg QD + MEK162 45 mg BID
- intervention Names
- Drug: LGX818
- Drug: MEK162
- label
- LGX818 450 mg + MEK162
- type
- EXPERIMENTAL
- description
- Vemurafenib 960 mg BID
- intervention Names
- Drug: vemurafenib
- label
- Vemurafenib
- type
- ACTIVE_COMPARATOR
- description
- LGX818 300 mg QD + MEK162 45 mg BID
- intervention Names
- Drug: LGX818
- Drug: MEK162
- label
- LGX818 300 mg + MEK162
- type
- EXPERIMENTAL
- description
- LGX818 300 mg QD
- intervention Names
- Drug: LGX818
- label
- LGX818
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- LGX818
- LGX818 300 mg + MEK162
- LGX818 450 mg + MEK162
- description
- LGX818- Orally 100 mg and 50 mg capsules
- name
- LGX818
- type
- DRUG
- arm Group Labels
- LGX818 300 mg + MEK162
- LGX818 450 mg + MEK162
- description
- MEK162- Orally 15 mg tablets
- name
- MEK162
- type
- DRUG
- arm Group Labels
- Vemurafenib
- description
- Tablets in bottles or blisters 240 mg
- name
- vemurafenib
- other Names
- Zelboraf
- PLX4032
- RO5185426
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 921
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- 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/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).
- measure
- 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)
- description
- 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.
- measure
- 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
- secondary Outcomes
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
- description
- 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.
- measure
- 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)
Full 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: 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)
Source references
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- DERIVED
- citation
- Dummer R, Ascierto PA, Gogas HJ, Arance A, Mandala M, Liszkay G, Garbe C, Schadendorf D, Krajsova I, Gutzmer R, Chiarion-Sileni V, Dutriaux C, de Groot JWB, Yamazaki N, Loquai C, Moutouh-de Parseval LA, Pickard MD, Sandor V, Robert C, Flaherty KT. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):603-615. doi: 10.1016/S1470-2045(18)30142-6. Epub 2018 Mar 21.
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- table or Metastatic Melanoma MEKTOVI in combination with encorafenib was evaluated in a randomized, active-controlled, open-label, multicenter trial (COLUMBUS; NCT01909453). Eligible patients were required to have BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma, as detected using the bioMerieux THxID™BRA
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- able or Metastatic Melanoma BRAFTOVI in combination with binimetinib was evaluated in a randomized, active-controlled, open-label, multicenter trial (COLUMBUS; NCT01909453). Eligible patients were required to have BRAF V600E or V600K mutation-positive unresectable or metastatic melanoma, as detected using the bioMerieux THxID™ BR
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- with BRAF V600 mutation-positive melanoma to MEKTOVI 45 mg twice daily in combination with encorafenib once daily across multiple clinical trials (NCT03915951, NCT01909453). The pooled safety population described in the WARNINGS AND PRECAUTIONS also reflect exposure of 98 patients with BRAF V600E mutation-positive metastatic non-
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- ong>Previously untreated or progression on or after first-line immunotherapy.</strong> An international, open-label, phase III trial (<a href="/clinicaltrials/NCT01909453">COLUMBUS</a> [NCT01909453]) included 577 patients with stage IIIB, IIIC, or IV melanoma and <em class="gene-name">BRAF</em> V600 pathogenic variants. Patients
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- progression on or after first-line immunotherapy.</strong> An international, open-label, phase III trial (<a href="/clinicaltrials/NCT01909453">COLUMBUS</a> [NCT01909453]) included 577 patients with stage IIIB, IIIC, or IV melanoma and <em class="gene-name">BRAF</em> V600 pathogenic variants. Patients were randomly assigned in
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- Updated: May 2, 2025
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- May 2, 2025
Preserved source evidence · Not medical advice