A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

A Phase Ib/II, Multicenter, Open-label, Dose Escalation Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF V600 - Dependent Advanced Solid Tumors

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01543698

Enrollment

189

Registered

2012-03-05

Start date

2012-05-28

Completion date

2023-03-09

Last updated

2024-03-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumors Harboring a BRAF V600 Mutation

Keywords

Advanced solid tumor,, BRAF V600 mutation

Brief summary

This is a multi-center, open-label, dose finding, Phase Ib dose escalation study to estimate the MTD(s) and/or RP2D(s) for the dual combination of LGX818 and MEK162 and the triple combination of LGX818 and MEK162 and LEE011, followed each independently by a Phase II part to assess the clinical efficacy and to further assess the safety of the combinations in selected patient populations. Oral LGX818 and MEK162 will be administered on a continuous schedule. Oral LEE011 will be administered once daily on a three weeks on, one week off schedule. Patients will be treated until progression of disease, unacceptable toxicity develops, or withdrawal of informed consent, whichever occurs first. A cycle is defined as 28 days. The dose escalation parts of the trial will be conducted in adult patients with BRAF V600-dependent advanced solid tumors and is expected to enroll at least 18 patients for the dual combination and at least 12 patients for the triple combination. The dose escalation will be guided by a Bayesian logistic regression model (BLRM). Following MTD/RP2D declaration, patients will be enrolled in three Phase II arms for the dual combination and one Phase II arm for the triple combination. All patients will be followed for 30 days for safety assessments after study drugs discontinuation. All patients enrolled in the Phase II part of the study will be followed for survival.

Interventions

DRUGLGX818

DRUGMEK162

DRUGLEE011

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage IIIB to IV per American Joint Committee on Cancer \[AJCC\]), or confirmed diagnosis of non-resectable advanced metastatic colorectal cancer (mCRC), or any other indication upon agreement with the Sponsor, whose disease has progressed despite previous antineoplastic therapy or for whom no further effective standard therapy is available * Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation * Evidence of measurable disease as determined by RECIST v1.1 * World Health Organization (WHO) Performance Status ≤ 2 * Negative serum pregnancy test within 72 hours prior to the first study dose in all women of childbearing potential

Exclusion criteria

Progressive disease following prior treatment with RAF-inhibitors in combination with MEK-inhibitors * Symptomatic or untreated leptomeningeal disease * Symptomatic brain metastases. Patients are not permitted to receive enzyme inducing anti-epileptic drugs * Known acute or chronic pancreatitis * History or current evidence of retinal disease, retinal vein occlusion or ophthalmopathy * Clinically significant cardiac disease * Patients with abnormal laboratory values at Screening/baseline * Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LGX818/MEK162 * Previous or concurrent malignancy * Pregnant or nursing (lactating) women * For addition of LEE011 in the triple combination, congenital long QT syndrome or family history of unexpected sudden cardiac death and/or hypokalemia CTCAE Grade ≥ 3, brain metastases at baseline, abnormal coagulation results PT/INR \>1.5 x ULN or aPTT \>1.5 x ULN. Other protocol-defined inclusion/

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011)	DLT was defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, as clinically relevant, as unrelated to disease, disease progression, inter-current illness, or concomitant medications, which occurred (less than equal to) \<=28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011 (cycle 1) and met the defined criteria for the study.
Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)	Phase 2: Week 16	DCR was defined as percentage of participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD). As per Response Evaluation Criteria in Solid tumors Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis less than (\<)10 millimeter \[mm\]). PR was defined as more than equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD).
Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A	Phase 2: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment for Phase 2 was 111.5 months]	ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30% decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.

Secondary

Measure	Time frame	Description
Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1	—
AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1	—
Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1	—
AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1	—
Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1	—
Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1	—
Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1	—
t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Phase 1b: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 1b was 118.3 months)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.
Objective Response Rate (ORR): Phase 1b	Phase 1b: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment in Phase 1b was 118.3 months)	ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.
Progression Free Survival (PFS): Phase 2	Phase 2: From start of study drug until documented PD or death due to any cause or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)	PFS was defined as the time from the start of study treatment to the date of the event defined as the first documented progression or death due to any cause. If a participant did not have an event, PFS was censored at the date of last adequate tumor assessment. Per RECIST 1.1, PD= 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 also demonstrate an absolute increase of at least 5 mm\^2. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.
Time to Response (TTR): Phase 2	Phase 2: From date of start of treatment until date of first documentation of objective tumor response (maximum exposure of treatment in Phase 2 was 111.5 months)	TTR was defined as the time from the first dose of study treatment to the first documentation of objective tumor response documented in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.
Duration of Response (DOR): Phase 2	Phase 2: From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first (maximum exposure of treatment in Phase 2 was 111.5 months)	DOR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.
Overall Survival (OS): Phase 2	Phase 2: From date of start of study treatment until date of death or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)	OS was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last contact. Analysis was performed using Kaplan-Meier method.
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	Phase 1b: Baseline	Molecular alterations of tumor tissues was determined using the following potential predictive markers: Biomarkers like V-raf murine sarcoma viral oncogene homolog B1 (BRAF),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), Phosphatase and tensin homolog (PTEN), Phosphatidylinositol 3' kinase catalytic alphapolypeptide (PIK3CA), Epidermal growth factor receptor (EGFR).
Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	Phase 2: Baseline	Molecular alterations of tumor tissues was determined using the following potential predictive markers: BRAF, HRAS, KRAS, Neuroblastoma RAS viral oncogene homolog (NRAS), PTEN, PIK3CA, Mitogen-activated protein kinase 1 (MAP2K1), Mitogen-activated protein kinase 2 (MAP2K2), EGFR.
Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 and 15 of Cycle 1	Accumulation ratio was calculated as AUCtau,ss/AUCtau.
Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Phase 2: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 2 was 111.5 months)	An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to CTCAE version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.
Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hours (hr) post dose on Day 1 of Cycle 1	AUCinf was reported in unit of measure as hour\nanogram per millilitre (h\ng/mL).

Countries

Australia, Belgium, Canada, France, Italy, Singapore, Spain, Switzerland, United States

Participant flow

Recruitment details

This study had 2 Phases- 1b and 2. Phase 1b enrolled participants with V-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600-dependent advanced solid tumors. Phase 2 enrolled participants with: BRAF V600 mutant metastatic colorectal cancer (mCRC) \[Arm 1, dual\]; BRAF V600 mutant melanoma who progressed after prior selective BRAF inhibitor treatment \[Arm 2, dual\]; metastatic BRAF mutant melanoma who were naïve to prior treatment with a selective BRAF inhibitor \[Arm 3, dual\]/ \[Arm A, triple\].

Pre-assignment details

A total of 189 participants were enrolled. Phase 1 b: 47 participants for dual combination and 21 participants for triple combination. Phase 2: a) Dual combination- Arm 1 (mCRC) =11 participants; Arm 2 (prior BRAFi melanoma) =26 participants; Arm 3 (BRAFi-naïve melanoma) =42 participants and b) Triple combination- Arm A (BRAFi-naïve melanoma) =42 participants. Dual combination of LGX818 (encorafenib) and MEK162 (binimetinib) and triple combination of LGX818, MEK162 and LEE011 (ribociclib).

Participants by arm

Arm	Count
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg Participants received Encorafenib 50 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	6
Phase 1b: Encorafenib 100 mg+ Binimetinib 45 mg Participants received Encorafenib 100 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg Participants received Encorafenib 200 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	4
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg Participants received Encorafenib 400 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	5
Phase 1b: Encorafenib 450 mg+ Binimetinib 45 mg Participants received Encorafenib 450 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	13
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg Participants received Encorafenib 600 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	8
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg Participants received Encorafenib 800 mg QD and Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks.	6
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 100 mg Participants received Encorafenib 200 mg QD, Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks and Ribociclib 100 mg QD orally for 3 weeks on, 1 week off schedule.	4
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 200 mg Participants received Encorafenib 200 mg QD, Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks and Ribociclib 200 mg QD orally for 3 weeks on, 1 week off schedule.	5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg Participants received Encorafenib 200 mg QD, Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks and Ribociclib 400 mg QD orally for 3 weeks on, 1 week off schedule.	6
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg + Ribociclib 600 mg Participants received Encorafenib 200 mg QD, Binimetinib 45 mg BID orally on a schedule of continuous 4 weeks and Ribociclib 600 mg QD orally for 3 weeks on, 1 week off schedule.	6
Phase 2: Arm 1 (mCRC): Encorafenib + Binimetinib Participants received Encorafenib at MTD (600 mg QD, permitted dose reduction to 450 mg QD) and Binimetinib 45 mg BID orally on a continuous schedule of 4 weeks until disease progression, unacceptable toxicity or withdrawal of informed consent, whichever occurred first.	11
Phase 2: Arm 2 (Prior BRAFi Melanoma): Encorafenib + Binimetinib Participants received Encorafenib at MTD (600 mg QD, permitted dose reduction to 450 mg QD) and Binimetinib 45 mg BID orally on a continuous schedule of 4 weeks.	26
Phase 2: Arm 3 (BRAFi-naïve Melanoma): Encorafenib + Binimetinib Participants received Encorafenib at MTD (600 mg QD, permitted dose reduction to 450 mg QD) and Binimetinib 45 mg BID orally on a continuous schedule of 4 weeks.	42
Phase 2: Arm A (BRAFi-naïve Melanoma): Encorafenib + Binimetinib + Ribociclib Participants received Encorafenib 200 mg QD (MTD), Binimetinib 45 mg BID orally on a continuous schedule of 4 weeks, and Ribociclib 600 mg QD orally for 3 weeks on, 1 week off schedule.	42
Total	189

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009	FG010	FG011	FG012	FG013	FG014
Phase 1b	Administrative problems	1	0	0	0	1	0	0	1	0	0	2	0	0	0	0
Phase 1b	Adverse Event	1	0	0	1	2	2	0	0	1	1	2	0	0	0	0
Phase 1b	Death	0	0	1	1	0	0	0	0	0	0	1	0	0	0	0
Phase 1b	Disease progression	2	4	3	2	10	6	5	3	4	5	1	0	0	0	0
Phase 1b	Protocol Violation	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Phase 1b	Withdrawal by Subject	0	1	0	1	0	0	1	0	0	0	0	0	0	0	0
Phase 2	Administrative problems	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1
Phase 2	Adverse Event	0	0	0	0	0	0	0	0	0	0	0	1	3	5	14
Phase 2	Death	0	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Phase 2	Disease progression	0	0	0	0	0	0	0	0	0	0	0	10	21	30	25
Phase 2	Protocol Violation	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Phase 2	Withdrawal by Subject	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1

Baseline characteristics

Characteristic	Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Phase 1b: Encorafenib 100 mg+ Binimetinib 45 mg	Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Phase 1b: Encorafenib 450 mg+ Binimetinib 45 mg	Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 100 mg	Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 200 mg	Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg + Ribociclib 600 mg	Phase 2: Arm 1 (mCRC): Encorafenib + Binimetinib	Phase 2: Arm 2 (Prior BRAFi Melanoma): Encorafenib + Binimetinib	Phase 2: Arm 3 (BRAFi-naïve Melanoma): Encorafenib + Binimetinib	Phase 2: Arm A (BRAFi-naïve Melanoma): Encorafenib + Binimetinib + Ribociclib	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	3 Participants	1 Participants	0 Participants	1 Participants	3 Participants	2 Participants	1 Participants	0 Participants	1 Participants	3 Participants	0 Participants	2 Participants	4 Participants	9 Participants	10 Participants	40 Participants
Age, Categorical Between 18 and 65 years	3 Participants	4 Participants	4 Participants	4 Participants	10 Participants	6 Participants	5 Participants	4 Participants	4 Participants	3 Participants	6 Participants	9 Participants	22 Participants	33 Participants	32 Participants	149 Participants
Race/Ethnicity, Customized Ethnicity Chinese	2 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	5 Participants
Race/Ethnicity, Customized Ethnicity Hispanic/Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	4 Participants
Race/Ethnicity, Customized Ethnicity Other	4 Participants	5 Participants	2 Participants	5 Participants	12 Participants	8 Participants	6 Participants	4 Participants	5 Participants	6 Participants	6 Participants	11 Participants	24 Participants	41 Participants	41 Participants	180 Participants
Race/Ethnicity, Customized Race Asian	2 Participants	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	6 Participants
Race/Ethnicity, Customized Race Caucasian	4 Participants	5 Participants	2 Participants	5 Participants	12 Participants	8 Participants	6 Participants	4 Participants	5 Participants	6 Participants	6 Participants	11 Participants	24 Participants	37 Participants	42 Participants	177 Participants
Race/Ethnicity, Customized Race Other	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	5 Participants	0 Participants	6 Participants
Sex: Female, Male Female	2 Participants	3 Participants	4 Participants	1 Participants	5 Participants	3 Participants	4 Participants	1 Participants	4 Participants	1 Participants	4 Participants	3 Participants	11 Participants	12 Participants	19 Participants	77 Participants
Sex: Female, Male Male	4 Participants	2 Participants	0 Participants	4 Participants	8 Participants	5 Participants	2 Participants	3 Participants	1 Participants	5 Participants	2 Participants	8 Participants	15 Participants	30 Participants	23 Participants	112 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk
deaths Total, all-cause mortality	1 / 6	0 / 5	1 / 4	2 / 5	2 / 13	0 / 8	1 / 6	0 / 4	1 / 5	0 / 6	2 / 6	9 / 11	22 / 26	22 / 42	28 / 42
other Total, other adverse events	6 / 6	5 / 5	4 / 4	5 / 5	13 / 13	8 / 8	6 / 6	4 / 4	5 / 5	5 / 6	6 / 6	11 / 11	26 / 26	39 / 42	42 / 42
serious Total, serious adverse events	4 / 6	2 / 5	2 / 4	2 / 5	5 / 13	4 / 8	4 / 6	2 / 4	3 / 5	3 / 6	2 / 6	5 / 11	13 / 26	18 / 42	21 / 42

Outcome results

Primary

Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)

DCR was defined as percentage of participants with a best overall response of complete response (CR), partial response (PR) or stable disease (SD). As per Response Evaluation Criteria in Solid tumors Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis less than (\<)10 millimeter \[mm\]). PR was defined as more than equal to (\>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. SD was defined as neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD).

Time frame: Phase 2: Week 16

Population: Full Analysis Set (FAS) included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Value (NUMBER)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)	63.6 Percentage of participants

Primary

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b

DLT was defined as an adverse event or abnormal laboratory value assessed as at least possibly related to the study medication, as clinically relevant, as unrelated to disease, disease progression, inter-current illness, or concomitant medications, which occurred (less than equal to) \<=28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011 (cycle 1) and met the defined criteria for the study.

Time frame: Phase 1b: Cycle 1 (28 days following the first dose of LGX818 and MEK162 or LGX818 and MEK162 and LEE011)

Population: Dose Determining Set (DDS) included all Phase 1b participants from the safety set who either completed a minimum exposure requirement and had sufficient safety evaluations or discontinued prematurely due to a DLT. All participants reported under Number of Participants Analyzed contributed data to this outcome measure.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	1 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b	0 Participants

Primary

Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A

ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30% decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.

Time frame: Phase 2: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment for Phase 2 was 111.5 months]

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Value (NUMBER)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A	42.3 Percentage of participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A	66.7 Percentage of participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A	59.5 Percentage of participants

Secondary

Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b

Accumulation ratio was calculated as AUCtau,ss/AUCtau.

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 and 15 of Cycle 1

Population: FAS evaluated. All participants reported under Number of Participants Analyzed contributed data to the table; however, may not have evaluable data for every row. Here, Number Analyzed signifies number of participants evaluable for specified rows.

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.51 Ratio	Standard Deviation 0.248
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.899 Ratio	Standard Deviation 0.542
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.857 Ratio	Standard Deviation 0.351
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.26 Ratio	Standard Deviation 0.152
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.601 Ratio	Standard Deviation 0.322
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.588 Ratio	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.285 Ratio	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.298 Ratio	Standard Deviation 0.0682
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.07 Ratio	Standard Deviation 0.142
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.954 Ratio	Standard Deviation 0.0302
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.348 Ratio	Standard Deviation 0.125
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	0.989 Ratio	Standard Deviation 0.353
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.546 Ratio	Standard Deviation 0.3
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.458 Ratio	Standard Deviation 0.188
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.03 Ratio	Standard Deviation 0.339
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.473 Ratio	Standard Deviation 0.215
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.499 Ratio	—
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	0.969 Ratio	Standard Deviation 0.297
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.19 Ratio	Standard Deviation 0.472
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.569 Ratio	Standard Deviation 0.0381
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.690 Ratio	Standard Deviation 0.291
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2.81 Ratio	Standard Deviation 0.619
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	0.640 Ratio	Standard Deviation 0.282
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.29 Ratio	Standard Deviation 0.572
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.460 Ratio	Standard Deviation 0.134
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	1.56 Ratio	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	1.93 Ratio	Standard Deviation 0.684
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	0.778 Ratio	Standard Deviation 0.102
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.841 Ratio	Standard Deviation 0.178
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	0.734 Ratio	Standard Deviation 0.404
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.726 Ratio	Standard Deviation 0.194
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.19 Ratio	Standard Deviation 0.324
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.833 Ratio	Standard Deviation 0.463
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	1.11 Ratio	Standard Deviation 0.753
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2.73 Ratio	Standard Deviation 0.517
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	0.910 Ratio	Standard Deviation 0.195
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.08 Ratio	Standard Deviation 0.316
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	0.806 Ratio	Standard Deviation 0.393
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2.97 Ratio	Standard Deviation 0.548
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	0.712 Ratio	Standard Deviation 0.168

Secondary

Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

AUCinf was reported in unit of measure as hour\*nanogram per millilitre (h\*ng/mL).

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hours (hr) post dose on Day 1 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2190 h*ng/mL	Standard Deviation 1350
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	321 h*ng/mL	Standard Deviation 225
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3740 h*ng/mL	Standard Deviation 2350
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1930 h*ng/mL	Standard Deviation 529
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11700 h*ng/mL	Standard Deviation 6200
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	271 h*ng/mL	Standard Deviation 28.9
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	631 h*ng/mL	Standard Deviation 296
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	22000 h*ng/mL	Standard Deviation 9790
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3730 h*ng/mL	Standard Deviation 2250
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	275 h*ng/mL	Standard Deviation 121
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	42000 h*ng/mL	Standard Deviation 23600
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1960 h*ng/mL	Standard Deviation 1140
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	361 h*ng/mL	Standard Deviation 184
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	36700 h*ng/mL	Standard Deviation 19400
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2750 h*ng/mL	Standard Deviation 1490
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	57400 h*ng/mL	Standard Deviation 27100
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	449 h*ng/mL	Standard Deviation 302
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3090 h*ng/mL	Standard Deviation 1600
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2340 h*ng/mL	Standard Deviation 462
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	361 h*ng/mL	Standard Deviation 78.1
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	40200 h*ng/mL	Standard Deviation 12100
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	194 h*ng/mL	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	1040 h*ng/mL	Standard Deviation 665
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2160 h*ng/mL	Standard Deviation 1580
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15000 h*ng/mL	Standard Deviation 7360
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	173 h*ng/mL	Standard Deviation 55.6
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	601 h*ng/mL	Standard Deviation 225
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3000 h*ng/mL	Standard Deviation 932
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	9960 h*ng/mL	Standard Deviation 5940
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	3030 h*ng/mL	Standard Deviation 1600
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	337 h*ng/mL	Standard Deviation 29.2
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3110 h*ng/mL	Standard Deviation 1450
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	18900 h*ng/mL	Standard Deviation 9900
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	7930 h*ng/mL	Standard Deviation 5180
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	1340 h*ng/mL	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	239 h*ng/mL	Standard Deviation 79.1
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2970 h*ng/mL	Standard Deviation 458
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	17400 h*ng/mL	Standard Deviation 9480
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2160 h*ng/mL	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	18200 h*ng/mL	Standard Deviation 10400

Secondary

Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2130 h*ng/mL	Standard Deviation 1330
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	307 h*ng/mL	Standard Deviation 222
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3700 h*ng/mL	Standard Deviation 2320
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1860 h*ng/mL	Standard Deviation 532
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11500 h*ng/mL	Standard Deviation 6070
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	265 h*ng/mL	Standard Deviation 27.9
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	585 h*ng/mL	Standard Deviation 304
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	22000 h*ng/mL	Standard Deviation 9750
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3600 h*ng/mL	Standard Deviation 2160
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	257 h*ng/mL	Standard Deviation 109
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	40200 h*ng/mL	Standard Deviation 21700
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1890 h*ng/mL	Standard Deviation 1110
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	338 h*ng/mL	Standard Deviation 162
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	36300 h*ng/mL	Standard Deviation 19000
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2650 h*ng/mL	Standard Deviation 1410
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	57000 h*ng/mL	Standard Deviation 26800
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	430 h*ng/mL	Standard Deviation 291
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3010 h*ng/mL	Standard Deviation 1560
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2280 h*ng/mL	Standard Deviation 477
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	344 h*ng/mL	Standard Deviation 82
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	40000 h*ng/mL	Standard Deviation 12100
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	98.9 h*ng/mL	Standard Deviation 25.9
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	845 h*ng/mL	Standard Deviation 504
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1790 h*ng/mL	Standard Deviation 979
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	14800 h*ng/mL	Standard Deviation 7140
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	152 h*ng/mL	Standard Deviation 32.3
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	397 h*ng/mL	Standard Deviation 145
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2900 h*ng/mL	Standard Deviation 939
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	9940 h*ng/mL	Standard Deviation 5900
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	2550 h*ng/mL	Standard Deviation 1280
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	322 h*ng/mL	Standard Deviation 23.5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2860 h*ng/mL	Standard Deviation 1320
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	18700 h*ng/mL	Standard Deviation 9730
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	6700 h*ng/mL	Standard Deviation 3720
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	758 h*ng/mL	Standard Deviation 231
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	230 h*ng/mL	Standard Deviation 79.1
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2900 h*ng/mL	Standard Deviation 453
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	17300 h*ng/mL	Standard Deviation 9300
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	1200 h*ng/mL	Standard Deviation 320
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	14500 h*ng/mL	Standard Deviation 7490

Secondary

Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1990 h*ng/mL	Standard Deviation 1130
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	276 h*ng/mL	Standard Deviation 184
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3690 h*ng/mL	Standard Deviation 2340
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1990 h*ng/mL	Standard Deviation 715
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	280 h*ng/mL	Standard Deviation 50.5
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11500 h*ng/mL	Standard Deviation 6070
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	372 h*ng/mL	Standard Deviation 320
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	22000 h*ng/mL	Standard Deviation 9750
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3300 h*ng/mL	Standard Deviation 1990
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1870 h*ng/mL	Standard Deviation 867
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	40200 h*ng/mL	Standard Deviation 21700
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	241 h*ng/mL	Standard Deviation 82.5
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	287 h*ng/mL	Standard Deviation 122
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	36100 h*ng/mL	Standard Deviation 19300
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2330 h*ng/mL	Standard Deviation 1220
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2790 h*ng/mL	Standard Deviation 1480
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	340 h*ng/mL	Standard Deviation 244
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	57000 h*ng/mL	Standard Deviation 26800
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	38100 h*ng/mL	Standard Deviation 11800
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	307 h*ng/mL	Standard Deviation 78.4
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2120 h*ng/mL	Standard Deviation 478
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	81.4 h*ng/mL	Standard Deviation 41
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	806 h*ng/mL	Standard Deviation 549
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1520 h*ng/mL	Standard Deviation 663
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11400 h*ng/mL	Standard Deviation 4530
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	156 h*ng/mL	Standard Deviation 53.8
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	397 h*ng/mL	Standard Deviation 145
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2470 h*ng/mL	Standard Deviation 878
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	9280 h*ng/mL	Standard Deviation 4190
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	2550 h*ng/mL	Standard Deviation 1280
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	259 h*ng/mL	Standard Deviation 54.3
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	168 h*ng/mL	Standard Deviation 109
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	12700 h*ng/mL	Standard Deviation 5020
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2020 h*ng/mL	Standard Deviation 843
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	6700 h*ng/mL	Standard Deviation 3720
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	758 h*ng/mL	Standard Deviation 231
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	161 h*ng/mL	Standard Deviation 81.9
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2320 h*ng/mL	Standard Deviation 635
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15800 h*ng/mL	Standard Deviation 7160
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	1200 h*ng/mL	Standard Deviation 320
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	14500 h*ng/mL	Standard Deviation 7490

Secondary

AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2950 h*ng/mL	Standard Deviation 1380
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	147 h*ng/mL	Standard Deviation 152
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2620 h*ng/mL	Standard Deviation 1260
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	5510 h*ng/mL	Standard Deviation 1280
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	173 h*ng/mL	Standard Deviation 125
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2610 h*ng/mL	Standard Deviation 873
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	118 h*ng/mL	Standard Deviation 70.7
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4620 h*ng/mL	Standard Deviation 1640
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2660 h*ng/mL	Standard Deviation 1900
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	119 h*ng/mL	Standard Deviation 96.5
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	10200 h*ng/mL	Standard Deviation 2280
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2110 h*ng/mL	Standard Deviation 1220
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	157 h*ng/mL	Standard Deviation 104
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15900 h*ng/mL	Standard Deviation 8730
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2550 h*ng/mL	Standard Deviation 901
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2590 h*ng/mL	Standard Deviation 1640
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	132 h*ng/mL	Standard Deviation 142
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	27300 h*ng/mL	Standard Deviation 17900
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	25300 h*ng/mL	Standard Deviation 7240
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	190 h*ng/mL	Standard Deviation 79.8
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2540 h*ng/mL	Standard Deviation 529
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	255 h*ng/mL	Standard Deviation 131
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	462 h*ng/mL	Standard Deviation 129
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2180 h*ng/mL	Standard Deviation 1180
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	6310 h*ng/mL	Standard Deviation 2340
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	149 h*ng/mL	Standard Deviation 136
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	729 h*ng/mL	Standard Deviation 267
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2820 h*ng/mL	Standard Deviation 954
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	8210 h*ng/mL	Standard Deviation 2550
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	1520 h*ng/mL	Standard Deviation 979
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	210 h*ng/mL	Standard Deviation 68.4
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	176 h*ng/mL	Standard Deviation 92.5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11800 h*ng/mL	Standard Deviation 7000
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2740 h*ng/mL	Standard Deviation 1230
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	5620 h*ng/mL	Standard Deviation 3730
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2150 h*ng/mL	Standard Deviation 399
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	169 h*ng/mL	Standard Deviation 48.5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2970 h*ng/mL	Standard Deviation 1180
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15700 h*ng/mL	Standard Deviation 6060
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	3260 h*ng/mL	Standard Deviation 891
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	10100 h*ng/mL	Standard Deviation 2970

Secondary

AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose,0.5,1.5, 2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2950 h*ng/mL	Standard Deviation 1380
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	261 h*ng/mL	Standard Deviation 136
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2620 h*ng/mL	Standard Deviation 1260
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2610 h*ng/mL	Standard Deviation 873
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	237 h*ng/mL	Standard Deviation 107
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	5510 h*ng/mL	Standard Deviation 1280
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	126 h*ng/mL	Standard Deviation 59.5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4620 h*ng/mL	Standard Deviation 1640
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2660 h*ng/mL	Standard Deviation 1900
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2110 h*ng/mL	Standard Deviation 1220
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	10200 h*ng/mL	Standard Deviation 2280
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	194 h*ng/mL	Standard Deviation 75.8
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	221 h*ng/mL	Standard Deviation 83.5
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15900 h*ng/mL	Standard Deviation 8730
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2550 h*ng/mL	Standard Deviation 901
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2590 h*ng/mL	Standard Deviation 1640
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	304 h*ng/mL	Standard Deviation 77.7
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	27300 h*ng/mL	Standard Deviation 17900
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	25300 h*ng/mL	Standard Deviation 7240
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	225 h*ng/mL	Standard Deviation 25.1
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2540 h*ng/mL	Standard Deviation 529
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	255 h*ng/mL	Standard Deviation 131
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	462 h*ng/mL	Standard Deviation 129
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2180 h*ng/mL	Standard Deviation 1180
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	6310 h*ng/mL	Standard Deviation 2340
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	265 h*ng/mL	Standard Deviation 33.4
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	729 h*ng/mL	Standard Deviation 267
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2820 h*ng/mL	Standard Deviation 954
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	8210 h*ng/mL	Standard Deviation 2550
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	1520 h*ng/mL	Standard Deviation 979
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	219 h*ng/mL	Standard Deviation 71.5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	207 h*ng/mL	Standard Deviation 69.7
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11800 h*ng/mL	Standard Deviation 7000
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2740 h*ng/mL	Standard Deviation 1230
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	5620 h*ng/mL	Standard Deviation 3730
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	2150 h*ng/mL	Standard Deviation 399
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	175 h*ng/mL	Standard Deviation 52.8
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2970 h*ng/mL	Standard Deviation 1180
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	15700 h*ng/mL	Standard Deviation 6060
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	3260 h*ng/mL	Standard Deviation 891
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	10100 h*ng/mL	Standard Deviation 2970

Secondary

Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	693 ng/mL	Standard Deviation 283
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	39.7 ng/mL	Standard Deviation 43.7
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	587 ng/mL	Standard Deviation 321
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	568 ng/mL	Standard Deviation 233
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	36.0 ng/mL	Standard Deviation 25.9
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	1190 ng/mL	Standard Deviation 409
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	27.3 ng/mL	Standard Deviation 12.6
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	1060 ng/mL	Standard Deviation 194
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	616 ng/mL	Standard Deviation 438
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	553 ng/mL	Standard Deviation 336
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3760 ng/mL	Standard Deviation 1380
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	31.7 ng/mL	Standard Deviation 25.9
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	38.8 ng/mL	Standard Deviation 21.8
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4320 ng/mL	Standard Deviation 2260
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	638 ng/mL	Standard Deviation 283
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	716 ng/mL	Standard Deviation 321
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	35.0 ng/mL	Standard Deviation 25.3
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	11100 ng/mL	Standard Deviation 14100
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	7320 ng/mL	Standard Deviation 2700
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	47.3 ng/mL	Standard Deviation 19.5
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	726 ng/mL	Standard Deviation 206
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	16.8 ng/mL	Standard Deviation 9.77
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	43.7 ng/mL	Standard Deviation 16.1
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	584 ng/mL	Standard Deviation 181
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	1670 ng/mL	Standard Deviation 453
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	38.3 ng/mL	Standard Deviation 25.4
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	49.7 ng/mL	Standard Deviation 19.5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	778 ng/mL	Standard Deviation 160
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2320 ng/mL	Standard Deviation 779
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	146 ng/mL	Standard Deviation 111
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	55.1 ng/mL	Standard Deviation 26.5
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	33.2 ng/mL	Standard Deviation 16.7
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2480 ng/mL	Standard Deviation 1090
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	563 ng/mL	Standard Deviation 262
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	493 ng/mL	Standard Deviation 258
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	155 ng/mL	Standard Deviation 30.5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	33.7 ng/mL	Standard Deviation 12.8
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	609 ng/mL	Standard Deviation 261
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2590 ng/mL	Standard Deviation 929
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	195 ng/mL	Standard Deviation 56.3
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	752 ng/mL	Standard Deviation 304

Secondary

Duration of Response (DOR): Phase 2

DOR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.

Time frame: Phase 2: From date of first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to underlying cancer, whichever occurred first (maximum exposure of treatment in Phase 2 was 111.5 months)

Population: FAS evaluated.Here Number of Participants Analyzed signifies the number of participants who were confirmed responders and were evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Duration of Response (DOR): Phase 2	7.1 Months
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Duration of Response (DOR): Phase 2	3.8 Months
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Duration of Response (DOR): Phase 2	10.9 Months
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Duration of Response (DOR): Phase 2	7.5 Months

Secondary

Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.36 Hour	Standard Deviation 0.427
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.82 Hour	Standard Deviation 0.757
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.68 Hour	Standard Deviation 0.605
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.37 Hour	Standard Deviation 0.704
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.65 Hour	Standard Deviation 0.351
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.00 Hour	Standard Deviation 0.0542
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.95 Hour	Standard Deviation 0.739
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2.88 Hour	Standard Deviation 0.121
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.10 Hour	Standard Deviation 0.522
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.58 Hour	Standard Deviation 0.737
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.19 Hour	Standard Deviation 2.13
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.51 Hour	Standard Deviation 0.472
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.64 Hour	Standard Deviation 0.604
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.47 Hour	Standard Deviation 0.402
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.22 Hour	Standard Deviation 0.439
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.21 Hour	Standard Deviation 0.55
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.28 Hour	Standard Deviation 0.546
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.12 Hour	Standard Deviation 0.314
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.99 Hour	Standard Deviation 0.601
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.37 Hour	Standard Deviation 0.517
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.04 Hour	Standard Deviation 0.0935
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	23.2 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	8.71 Hour	Standard Deviation 2.32
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3.73 Hour	Standard Deviation 1.78
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.25 Hour	Standard Deviation 0.375
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	3.39 Hour	Standard Deviation 1.57
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	15.4 Hour	Standard Deviation 6.92
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.45 Hour	Standard Deviation 1.19
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2.10 Hour	Standard Deviation 0.451
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	7.97 Hour	Standard Deviation 1.24
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.49 Hour	Standard Deviation 0.528
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3.11 Hour	Standard Deviation 1.01
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2.95 Hour	Standard Deviation 1.13
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	10.3 Hour	Standard Deviation 3.94
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	7.99 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.32 Hour	Standard Deviation 0.455
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	1.98 Hour	Standard Deviation 0.523
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2.59 Hour	Standard Deviation 0.567
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	15.9 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	7.71 Hour	Standard Deviation 0.408

Secondary

Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose, 0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 1 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	635 ng/mL	Standard Deviation 402
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	79.3 ng/mL	Standard Deviation 55.3
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	855 ng/mL	Standard Deviation 480
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	587 ng/mL	Standard Deviation 147
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	75.3 ng/mL	Standard Deviation 10.7
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	1930 ng/mL	Standard Deviation 652
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	90.8 ng/mL	Standard Deviation 88
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3820 ng/mL	Standard Deviation 1550
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	986 ng/mL	Standard Deviation 771
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	532 ng/mL	Standard Deviation 227
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	6930 ng/mL	Standard Deviation 1950
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	67.9 ng/mL	Standard Deviation 32
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	85.1 ng/mL	Standard Deviation 34.9
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	7620 ng/mL	Standard Deviation 3350
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	807 ng/mL	Standard Deviation 398
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	901 ng/mL	Standard Deviation 480
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	93.5 ng/mL	Standard Deviation 67
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	10300 ng/mL	Standard Deviation 3170
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	7880 ng/mL	Standard Deviation 2910
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	81.1 ng/mL	Standard Deviation 32.4
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	621 ng/mL	Standard Deviation 160
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	5.90 ng/mL	Standard Deviation 1.73
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	74.2 ng/mL	Standard Deviation 37.5
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	462 ng/mL	Standard Deviation 85.6
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	2920 ng/mL	Standard Deviation 499
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	41.8 ng/mL	Standard Deviation 13.2
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	28.7 ng/mL	Standard Deviation 7.82
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	867 ng/mL	Standard Deviation 232
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3190 ng/mL	Standard Deviation 1010
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	219 ng/mL	Standard Deviation 95.2
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	83.2 ng/mL	Standard Deviation 28.2
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	40.2 ng/mL	Standard Deviation 22.3
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3450 ng/mL	Standard Deviation 1140
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	560 ng/mL	Standard Deviation 213
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	554 ng/mL	Standard Deviation 251
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	58.0 ng/mL	Standard Deviation 39.6
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	45.0 ng/mL	Standard Deviation 25.4
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	703 ng/mL	Standard Deviation 222
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4200 ng/mL	Standard Deviation 1020
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	73.8 ng/mL	Standard Deviation 24.3
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	1220 ng/mL	Standard Deviation 701

Secondary

Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b

Molecular alterations of tumor tissues was determined using the following potential predictive markers: Biomarkers like V-raf murine sarcoma viral oncogene homolog B1 (BRAF),V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), Phosphatase and tensin homolog (PTEN), Phosphatidylinositol 3' kinase catalytic alphapolypeptide (PIK3CA), Epidermal growth factor receptor (EGFR).

Time frame: Phase 1b: Baseline

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	1 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	5 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	4 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	1 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	1 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	3 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	4 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	2 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	1 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	7 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	2 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	7 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	1 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	1 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	3 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	3 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	4 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	5 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	PTEN	1 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	KRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	BRAF	4 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b	EGFR	0 Participants

Secondary

Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2

Molecular alterations of tumor tissues was determined using the following potential predictive markers: BRAF, HRAS, KRAS, Neuroblastoma RAS viral oncogene homolog (NRAS), PTEN, PIK3CA, Mitogen-activated protein kinase 1 (MAP2K1), Mitogen-activated protein kinase 2 (MAP2K2), EGFR.

Time frame: Phase 2: Baseline

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	BRAF	4 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	HRAS	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	KRAS	2 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	NRAS	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PTEN	1 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PIK3CA	2 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K1	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K2	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	ARAF	0 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	EGFR	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	KRAS	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	ARAF	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	NRAS	2 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PTEN	6 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PIK3CA	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K1	3 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	EGFR	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K2	0 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	BRAF	15 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	HRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K2	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K1	1 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	EGFR	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	BRAF	20 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	NRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PIK3CA	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	ARAF	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	HRAS	0 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PTEN	5 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	KRAS	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PTEN	5 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K2	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	PIK3CA	2 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	EGFR	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	MAP2K1	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	HRAS	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	KRAS	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	NRAS	0 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	BRAF	30 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2	ARAF	0 Participants

Secondary

Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to CTCAE version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.

Time frame: Phase 2: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 2 was 111.5 months)

Population: Safety set included all participants who received at least one dose of LGX818 or MEK162 or LEE011 and had at least one valid post-baseline safety assessment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Overall Grades	11 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Grade 3/4	5 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Grade 3/4	15 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Overall Grades	26 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Overall Grades	42 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Grade 3/4	27 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Overall Grades	42 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2	Grade 3/4	34 Participants

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b

An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were those events with onset dates occurring during the on-treatment period (the time from the Day 1 up to 30 days after last dose). AEs were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 indicates Mild AE, Grade 2 indicates Moderate AE, Grade 3 indicates severe AE, and grade 4 indicates life-threatening consequences; urgent intervention indicated. Grade 5 indicates death related to AE.

Time frame: Phase 1b: Day 1 up to 30 days after last dose (maximum treatment exposure for Phase 1b was 118.3 months)

Population: Safety set included all participants who received at least one dose of LGX818 or MEK162 or LEE011 and had at least one valid post-baseline safety assessment.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	6 Participants
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	5 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	5 Participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	2 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	4 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	2 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	5 Participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	4 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	13 Participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	8 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	6 Participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	8 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	6 Participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	6 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	4 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	4 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	5 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	4 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	6 Participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	6 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Overall Grades	6 Participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b	Grade 3/4	6 Participants

Secondary

Objective Response Rate (ORR): Phase 1b

ORR was defined as the percentage of participants with a best overall response of CR or PR. As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters.

Time frame: Phase 1b: From Day 1 of dosing till complete response or partial response achieved (maximum exposure of treatment in Phase 1b was 118.3 months)

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Value (NUMBER)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	66.7 Percentage of participants
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	40.0 Percentage of participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	25.0 Percentage of participants
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	40.0 Percentage of participants
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	53.8 Percentage of participants
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	25.0 Percentage of participants
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	Objective Response Rate (ORR): Phase 1b	50.0 Percentage of participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	Objective Response Rate (ORR): Phase 1b	75.0 Percentage of participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	Objective Response Rate (ORR): Phase 1b	60.0 Percentage of participants
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	Objective Response Rate (ORR): Phase 1b	66.7 Percentage of participants
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	Objective Response Rate (ORR): Phase 1b	66.7 Percentage of participants

Secondary

Overall Survival (OS): Phase 2

OS was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last contact. Analysis was performed using Kaplan-Meier method.

Time frame: Phase 2: From date of start of study treatment until date of death or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Value (MEDIAN)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Overall Survival (OS): Phase 2	9.5 Months
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Overall Survival (OS): Phase 2	11.4 Months
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Overall Survival (OS): Phase 2	23.1 Months
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Overall Survival (OS): Phase 2	21.8 Months

Secondary

Progression Free Survival (PFS): Phase 2

PFS was defined as the time from the start of study treatment to the date of the event defined as the first documented progression or death due to any cause. If a participant did not have an event, PFS was censored at the date of last adequate tumor assessment. Per RECIST 1.1, PD= 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 also demonstrate an absolute increase of at least 5 mm\^2. Unequivocal progression of existing non-target lesions. Kaplan-Meier method was used for analysis.

Time frame: Phase 2: From start of study drug until documented PD or death due to any cause or censoring date (maximum exposure of treatment in Phase 2 was 111.5 months)

Population: FAS included all participants who received at least one dose of LGX818 or MEK162 or LEE011.

Arm	Measure	Value (MEDIAN)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Progression Free Survival (PFS): Phase 2	5.4 Months
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Progression Free Survival (PFS): Phase 2	3.8 Months
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Progression Free Survival (PFS): Phase 2	7.5 Months
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Progression Free Survival (PFS): Phase 2	9.0 Months

Secondary

t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time frame: Phase 1b: Pre dose,0.5,1.5,2.5,4,6,8 and 24 hr post dose on Day 15 of Cycle 1

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.74 Hour	Standard Deviation 1.18
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	4.74 Hour	Standard Deviation 1.43
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	4.51 Hour	Standard Deviation 1.23
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	7.23 Hour	Standard Deviation 5.44
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.47 Hour	Standard Deviation 0.38
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	4.80 Hour	Standard Deviation 1.4
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3.28 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.07 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.32 Hour	Standard Deviation 1.25
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	4.20 Hour	Standard Deviation 1.36
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	4.61 Hour	—
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.21 Hour	Standard Deviation 0.724
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.79 Hour	Standard Deviation 1.23
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.57 Hour	Standard Deviation 0.688
Phase 1b: Encorafenib 450 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3.61 Hour	Standard Deviation 1.14
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.40 Hour	Standard Deviation 0.223
Phase 1b: Encorafenib 600 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	4.06 Hour	Standard Deviation 0.195
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.91 Hour	Standard Deviation 0.157
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	3.33 Hour	Standard Deviation 0.524
Phase 1b: Encorafenib 800 mg + Binimetinib 45 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.37 Hour	Standard Deviation 0.511
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	4.04 Hour	Standard Deviation 2.03
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	18.3 Hour	Standard Deviation 3.23
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.98 Hour	Standard Deviation 0.331
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	13.2 Hour	Standard Deviation 2.26
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 100 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	5.12 Hour	—
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	2.67 Hour	Standard Deviation 1.4
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	15.7 Hour	Standard Deviation 6.62
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.24 Hour	Standard Deviation 0.776
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	2.58 Hour	Standard Deviation 0.626
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg + Ribociclib 200 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	11.4 Hour	Standard Deviation 6.07
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	8.49 Hour	Standard Deviation 2.8
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	3.69 Hour	Standard Deviation 1.16
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	4.00 Hour	Standard Deviation 0.922
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	15.0 Hour	Standard Deviation 6.27
Phase 1b: Encorafenib 200 mg+ Binimetinib 45 mg+ Ribociclib 400 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	3.44 Hour	Standard Deviation 0.115
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Ribociclib	18.6 Hour	Standard Deviation 2.76
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Encorafenib	3.52 Hour	Standard Deviation 0.237
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Binimetinib	5.21 Hour	Standard Deviation 1.75
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Ribociclib	10.3 Hour	Standard Deviation 5.32
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg+ Ribociclib 600 mg	t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b	Metabolite of Binimetinib	4.38 Hour	Standard Deviation 2.14

Secondary

Time to Response (TTR): Phase 2

TTR was defined as the time from the first dose of study treatment to the first documentation of objective tumor response documented in participants with confirmed objective response (CR or PR). As per RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease. All nodes, both target and non-target, must have a reduction in short axis \<10 mm. PR was defined as \>= 30 % decrease under baseline of sum of diameters of all target lesions taking as reference the baseline sum of diameters. Kaplan-Meier method was used for analysis.

Time frame: Phase 2: From date of start of treatment until date of first documentation of objective tumor response (maximum exposure of treatment in Phase 2 was 111.5 months)

Population: FAS evaluated.Here Number of Participants Analyzed signifies the number of participants who were confirmed responders and were evaluable for this outcome measure.

Arm	Measure	Value (MEDIAN)
Phase 1b: Encorafenib 50 mg + Binimetinib 45 mg	Time to Response (TTR): Phase 2	2.6 Months
Phase 1b: Encorafenib 100 mg + Binimetinib 45 mg	Time to Response (TTR): Phase 2	1.8 Months
Phase 1b: Encorafenib 200 mg + Binimetinib 45 mg	Time to Response (TTR): Phase 2	1.0 Months
Phase 1b: Encorafenib 400 mg + Binimetinib 45 mg	Time to Response (TTR): Phase 2	1.9 Months

Source: ClinicalTrials.gov · Data processed: Mar 4, 2026

A Phase Ib/II Study of LGX818 in Combination With MEK162 in Adult Patients With BRAF Dependent Advanced Solid Tumors

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Disease Control Rate (DCR) at Week 16: Phase 2, Arm 1 (mCRC Participants)

Number of Participants With Dose Limiting Toxicities (DLTs): Phase 1b

Objective Response Rate (ORR): Phase 2, Arms 2, 3 and A

Accumulation Ratio (RA) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b

Area Under the Concentration-time Curve From Time Zero to Infinity With Extrapolation of the Terminal Phase (AUCinf) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Area Under the Concentration-Time Curve From Time Zero to Tau After First Dose (AUCtau) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Area Under the Concentration-Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

AUClast at Steady State (AUClast,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

AUCtau at Steady State (AUCtau,ss) of Encorafenib, Binimetinib and Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Cmax at Steady State (Cmax,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Duration of Response (DOR): Phase 2

Elimination Half-life (t1/2) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Maximum Observed Plasma Concentration (Cmax) of Encorafenib, Binimetinib, Ribociclib Metabolite of Binimetinib and Ribociclib: Phase 1b

Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 1b

Number of Participants With Molecular Alterations of Tumor Tissues Using Potential Predictive Markers: Phase 2

Number of Participants With TEAEs: Overall Grades and AEs of Grade 3/4: Phase 2

Number of Participants With Treatment Emergent Adverse Events (TEAEs): Overall Grades and AEs of Grade 3/4: Phase 1b

Objective Response Rate (ORR): Phase 1b

Overall Survival (OS): Phase 2

Progression Free Survival (PFS): Phase 2

t1/2 at Steady State (t1/2,ss) of Encorafenib, Binimetinib, Ribociclib, Metabolite of Binimetinib and Ribociclib: Phase 1b

Time to Response (TTR): Phase 2