DLT: any adverse event (AE) or laboratory abnormality not explained by underlying disease/disease progression/intercurrent illness/concomitant therapies/resulting in inability to tolerate 75% of planned dose of binimetinib or encorafenib during Cycle 1. Left ventricular ejection fraction (LVEF) >10%, Grade (G)>=3 cardiac disorders; G3/4 hypertension vascular disorders; G3/4 rash, hand foot skin reaction, photosensitivity; G3/4 diarrhea, nausea/vomiting Total bilirubin (TBL) G>=3 (>3.0*upper limit of normal [ULN)]);AST/ALT>5-8*ULN>5 days,>8*ULN,>3*ULN concurrent TBL>2*ULN;G>=3 serum creatinine, CK elevation, ECG QTcF prolonged,G3 troponin, electrolyte>72 hours,G3/4 amylase/lipase.G4 ANC, platelet count>7 days;G3/4 platelet count, other AE except lymphopenia. G>=3 retinopathy, other disorder>21 days; G2 uveitis/eye pain/blurred vision/decreased visual acuity; G4 other disorder; Other hematologic/non hematologic G>=3 AE. This outcome measure was planned to be analyzed in SLI phase only.

The dose-determining set included all participants enrolled in the high-dose treatment arm in the safety lead-in who completed one 28-day cycle of treatment and received at least 75 percentage (%) of the planned cumulative dose of both study drugs or discontinued treatment because of DLT.

AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs: events between first dose of study drug up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurred first. Grades by NCI CTCAE v.4.03: Grade 1= asymptomatic or mild , clinical or diagnostic observations only, intervention not indicated; Grade 2= moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3= severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated; Grade 5= death related to AE. Number of participants with AEs per maximum grades were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

Hepatology laboratory abnormalities included following parameters: alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT or AST greater than or equal to (>=) 3*upper limit normal (ULN), >=5*ULN, >=10*ULN, >=20*ULN; total bilirubin (TBILI): >=2*ULN; ALT >=3*ULN and TBILI >=2*ULN; AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP >2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP <=2*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. Here, "Number Analyzed" signifies participants evaluable for specified rows. This outcome measure was planned to be analyzed in SLI phase only.

Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine kinase (CK) increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. Here, "Number Analyzed" signifies participants evaluable for specified rows. This outcome measure was planned to be analyzed in SLI phase only.

Vital signs included: systolic and diastolic blood pressure (BP),pulse rate,weight and temperature.Systolic and diastolic BP was measured in millimeters of mercury (mmHg) based on criteria:High Systolic BP:>=160 mmHg and increase >=20 mmHg from baseline;High Diastolic BP:>=100 mmHg and increase>=15 mmHg from baseline;Low Systolic BP:<=90 mmHg with decrease from baseline of >=20 mmHg;Low Diastolic BP:<=50 mmHg with decrease from baseline of >=15 mmHg;Pulse rate was measured in beats per minute (bpm) based on criteria:High pulse rate >=120 bpm with increase from baseline of >=15 bpm;Low pulse rate <=50 bpm with decrease from baseline of >=15 bpm;Weight was measured in in kilogram (kg) based on criteria:Increase from baseline of >=10%,:>=20% decrease from baseline;Temperature was measured in degree Celsius (C) based on criteria:High body temperature >=37.5 degree C,Low body temperature <=36 degree C.Only those vital signs parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, number of participants with notable abnormal ECG values included: Fridericia's Correction Formula (QTcF) values in millisecond (msec) based on following criteria: 1) Increase from baseline >30 msec; 2) Increase from baseline >60 msec; 3) New >450 msec; 4) New >480 msec; and 5) New >500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline >25% and to a value >100; 2) Decrease from baseline >25% and to a value <50. Only those ECG parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

An AE is any untoward medical occurrence in clinical investigation participant administered a product or medical device; event need not necessarily to have a causal relationship with treatment or usage. In this outcome measure, number of participants with incidence of dose interruptions, dose modifications and discontinuations due to AEs were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

BMRR was reported in terms of percentage of participants who achieved a confirmed best overall response (BOR) of confirmed complete response (CR) or partial response (PR) in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurred first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in phase 2 only.

Extracranial response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR in extracranial lesions by investigator assessment per RECIST v1.1. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The safety set included all participants who received at least 1 dose of any study drug.

Global response rate was defined as the percentage of participants with a BOR of confirmed CR or confirmed PR by investigator assessment in brain metastasis and extracranial lesions per combined mRECIST v1.1 and RECIST v1.1, respectively. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline).

The safety set included all participants who received at least 1 dose of any study drug.

DCR was defined as the percentage of participants with a BOR of CR, PR or stable disease (SD) by Investigator assessment per mRECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started.

The safety set included all participants who received at least 1 dose of any study drug.

DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum demonstrates an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression.

The safety set included all participants who received at least 1 dose of any study drug.

DCR was defined as the percentage of participants with a BOR of CR, PR or SD by Investigator assessment per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must be <10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to quality for PD. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm.

The safety set included all participants who received at least 1 dose of any study drug.

DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.

The safety set included all participants who received at least 1 dose of any study drug.

DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes must be <10 mm on the short axis. PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum of the diameters (e.g., percent change from baseline). DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.

The safety set included all participants who received at least 1 dose of any study drug.

DOR: time from date of first radiographic response (CR or PR) to earliest documented disease progression or death due to any cause. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. DOR (months) = (date of event or censoring - date of first CR or PR + 1)/30.4375. If a participant with a CR or PR did not have an event at time of analysis cutoff or with an event more than 16 weeks (for first 11 cycles after treatment start date) or 24 weeks (after Cycle 11) after last adequate tumor assessment, participant was censored on date of last adequate tumor assessment that documented no progression.

The safety set included all participants who received at least 1 dose of any study drug. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for specified rows. Data has been presented per participant as data was not summarized due to due to limited number of participants with events.

PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started (e.g., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase of at least 5 mm. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.

The safety set included all participants who received at least 1 dose of any study drug. Here, 'Number Analyzed' signifies participants evaluable for specified rows. Data has been presented per participant as data was not summarized due to due to limited number of participants with events.

PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression (PD) by Investigator assessment, or death due to any cause, whichever occurs first. PD: at least a 20% increase in the sum of the diameters of target lesions, taking as a reference the smallest sum of diameters recorded since the treatment started (i.e., percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of at least 5 mm. Global tumor assessment consists of brain metastasis and extracranial lesions. If a participant did not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment.

The safety set included all participants who received at least 1 dose of any study drug. Here, 'Number Analyzed' signifies participants evaluable for specified rows. Data has been presented per participant as data was not summarized due to limited number of participants with events.

BMRR: percentage of participants who achieved a confirmed best overall response (BOR) of confirmed CR or PR in brain metastasis per mRECIST v1.1 from date of first dose until disease progression, death due to any cause, or start of subsequent anticancer therapy, whichever occurs first. BOR: best response recorded from date of first dose of study treatment until progression by investigator assessment at each time point. CR: Disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (e.g., percent change from baseline).

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in SLI phase only.

Overall survival (OS) was defined as the time from date of the first dose of study treatment to the date of death due to any cause. If a death was not observed by the date of the analysis cutoff, OS was censored at the date of last contact. OS (months) = (date of death or censoring - date of first dose +1)/30.4375

Data was not collected due to the premature termination of the study and consequent lack of meaningful data, data are not available and no analyses were performed.

AE was any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship.TEAEs were events between 1st dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state or start of subsequent anticancer drug therapy minus 1 day, whichever occurs first.Severity was graded by NCI CTCAE v.4.03.Grade 1:asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL;Grade 4:life-threatening consequence, urgent intervention indicated; Grade 5:death related to AE. Only those categories in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in phase 2 only.

Hepatology laboratory abnormalities included following parameters: ALT, AST, ALT or AST >=3*ULN, >=5*ULN, >=10*ULN, >=20*ULN; TBILI: >=2*ULN; ALT >=3*ULN and TBILI >=2*ULN; AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP >2*ULN; ALT or AST >=3*ULN and TBILI >=2*ULN and ALP <=2*ULN or missing. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in phase 2 only.

Hematology and coagulation laboratory test included: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, and white blood cell decreased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for hematology and coagulation laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. Here, "Number Analyzed" signifies participants evaluable for specified rows. This outcome measure was planned to be analyzed in phase 2 only.

Biochemistry laboratory test included: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, CK increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase increased, and serum amylase increased. Laboratory results were categorically summarized according to the NCI-CTCAE criteria v4.03. Grade 1= mild; Grade 2= moderate; Grade 3= severe and Grade 4= life-threatening or disabling. Grade 0 was assigned for all non-missing values not graded as 1 or higher per CTCAE criteria. Number of participants with shift from baseline for biochemistry laboratory test were assessed. Only those laboratory test parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. Here, "Number Analyzed" signifies participants evaluable for specified rows. This outcome measure was planned to be analyzed in phase 2 only.

In this outcome measure, number of participants with notable abnormal vital signs included: systolic and diastolic BP in mmHg based on following criteria: 1) High Systolic BP: >=160 mmHg and an increase >=20 mmHg from baseline; 2) High Diastolic BP: >=100 mmHg and an increase >=15 mmHg from baseline; 3) Low Systolic BP: <=90 mmHg with decrease from baseline of >=20 mmHg; 4) Low Diastolic BP: <=50 mmHg with decrease from baseline of >=15 mmHg; pulse rate in bpm based on following criteria: 1) High pulse rate >=120 bpm with increase from baseline of >=15 bpm; 2) Low pulse rate <=50 bpm with decrease from baseline of >=15 bpm; weight in kg based on following criteria: 1) Weight: Increase from baseline of >=10%, 2) Weight: >=20 % decrease from baseline; temperature in degree C based on following criteria: 1) High body temperature >=37.5 degree C, 2) Low body temperature <=36 degree C. Only those vital signs parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in phase 2 only.

In this outcome measure, number of participants with notable abnormal ECG values included: QTcF values in msec based on following criteria: 1) increase from baseline >30 msec; 2) increase from baseline >60 msec; 3) new >450 msec; 4) new >480 msec; and 5) new >500 msec; heart rate values in bpm based on following criteria: 1) Increase from baseline >25% and to a value >100; 2) Decrease from baseline >25% and to a value <50. Only those vital ECG parameters in which at least 1 participant had data were reported.

The safety set included all participants who received at least 1 dose of any study drug. This outcome measure was planned to be analyzed in phase 2 only.

In this outcome measure, plasma concentrations (in nanogram per milliliter [ng/mL]) of encorafenib and its metabolite LHY746 at Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15), Cycle 2 Day 1 (C2D1), and Cycle 3 Day 1 (C3D1) at different time points were reported.

The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, plasma concentrations of binimetinib and its metabolite AR00426032 at C1D1, C1D15, C2D1, and C3D1 at different time points were reported.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of encorafenib and its metabolite LHY746 in nanogram*hour per milliliter (ng*hr/mL) at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from zero to 6 hours (AUC 0-6) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from zero to the last measurable time point (AUClast) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, area under the plasma concentration-time curve from time zero to the last measurable time point Tau (AUCtau) of encorafenib and its metabolite LHY746 over a dosing interval (6 hours as appropriate) of C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, maximum observed plasma concentration (Cmax) after administration of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, maximum observed plasma concentration (Cmax) after administration of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, minimum observed plasma concentration (Cmin) after administration of encorafenib and its metabolite LHY746 at C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, minimum observed plasma concentration (Cmin) after administration of binimetinib and its metabolite AR00426032 at C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of encorafenib and its metabolite LHY746 at C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, measured concentration at the end of a dosing interval (Ctrough) of binimetinib and its metabolite AR00426032 at C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, time to reach maximum concentration (Tmax) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, time to reach maximum concentration (Tmax) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, time of last PK sample (Tlast) of encorafenib and its metabolite LHY746 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since encorafenib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration on 24 hours for encorafenib and LHY746 on Cycle 1 Day 15 during the analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 24 hours for encorafenib and LHY746.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, time of last PK sample (Tlast) of binimetinib and its metabolite AR00426032 at C1D1, and C1D15 were assessed. As outlined in the prespecified Statistical Analysis Plan for the study, since binimetinib was administered in continuous cycles, the pre-dose sample on Cycle 2 Day 1 was assumed to be at steady state and was interpolated as the concentration for 12 hours for binimetinib and AR00426032 on Cycle 1 Day 15 for the noncompartmental analysis. In doing so, the reported Tlast values from the noncompartmental analysis (NCA) are 12 hours for binimetinib and AR00426032.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 AUC0-6 divided by C1D1 AUC0-6 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, accumulation ratio of encorafenib and its metabolite LHY746 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, accumulation ratio of binimetinib and its metabolite AR00426032 calculated as: C1D15 Cmax divided by C1D1 Cmax was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, ratio of AUClast values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/binimetinib at C1D1, and C1D15 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for LHY746/encorafenib at C1D1, and C1D15 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.

In this outcome measure, ratio of Cmax values of the metabolite compared to parent, corrected for molecular weight, for AR00426032/ binimetinib at C1D1, and C1D15 was assessed.

The PK set included all participants who received at least 1 dose of any study drug and had at least 1 PK blood collection after the first dose of study drug with associated bioanalytical results. Here 'Overall Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable at specified time points. This outcome measure was planned to be analyzed in SLI phase only.