Safety Lead in (SLI) and Phase 3: Incidence and severity of Adverse Events (AEs) and changes in clinical laboratory parameters, vital signs, and cardiac assessments.

AEs, laboratory parameters, vital signs and cardiac abnormalities will be graded according to the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.03).

Time from first dose of study intervention through 28 days after the last dose of study intervention.

Safety Lead in (SLI) and Phase 3: Objective Response (OR)

OR is defined as confirmed Best Overall Response (BOR) of either CR or PR as determined by investigator assessment per RECIST v1.1

Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks).

Safety Lead in (SLI) and Phase 3: Disease Control (DC)

DC is defined as confirmed BOR of CR, PR or SD, as determined by BICR and investigator assessment per RECIST v1.1.

Time from the date after the first dose of first dose (SLI) or the date of randomization (Phase 3) until documented PD, or start of subsequent anticancer therapy (approximately every 9 weeks)

Safety Lead in (SLI) and Phase 3: Time to Response (TTR)

TTR is defined as the time from the date of randomization to the date of first documented response (CR or PR), as determined by BICR and investigator or assessment per RECIST v1.1.

Time from the date of randomization to the date of first documented response (CR or PR), as determined by investigator assessment per RECIST v1 (approximately every 9 weeks)

Phase 3: Overall Survival (OS)

OS is defined as the time from the date of randomization to the date of death due to any cause

Time from the date of randomization to the date of death due to any cause.

Safety Lead In (SLI) and Phase 3: Progression Free Survival (PFS) by Investigator and BICR assessment

PFS by investigator is defined as the time from the date of randomization to the first date of documented disease progression as determined by investigator and BICR assessment per RECIST 1.1 or death due to any cause, whichever occurs first.

The time from the date of randomization to the date of first documented disease progression, as determined by investigator and BICR assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)

Phase 3: Duration of Response (DOR)

DOR is defined as the time from the date of first documented response to the date of first documented disease progression, as determined by BICR and investigator assessment or death due to any cause, whichever occurs first.

Time from date of first documented response (CR or PR) to the date of first documented disease progression, as determined by BICR and investigator assessment per RECIST v1.1, or death due to any cause, whichever occurs first (approximately every 9 weeks)

Safety Lead in (SLI): Plasma concentration-time profiles and Pharmacokinetic (PK) parameter estimates for encorafenib and binimetinib.

To measure plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Cycle 2, Day 1

Phase 3: Plasma concentrations of encorafenib and binimetinib.

To measure the plasma concentrations of encorafenib and its metabolite (LHY746), and binimetinib and its metabolite (AR00426032)

Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1 (Each Cycle is 21 days)

Phase 3: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30): change from baseline in the global health status/QoL score.

EORTC QLQ-30 includes 5 functional scales (physical, role, emotional, cognitive and social functioning), 3 symptom scales (fatigue, nausea/vomiting, and pain), 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial impact) and a global health status/Quality of Life scale

Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months

Phase 3: Change from baseline in Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale score.

The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire, melanoma-specific items, and items related to melanoma surgery

Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months

Phase 3: Change from baseline in 5-level EuroQol-5D (EQ-5D-5L) index score and visual analog scale (VAS)

The EQ-5D-5L is a standardized measure of health utility that provides a single index value of health status and contains 1 item for each of 5 dimensions of HRQoL (ie, mobility, self-care, usual activities, pain or discomfort, and anxiety or depression).

Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months

Phase 3: Change from baseline in Patient Global Impression of Severity (PGIS) score

The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe".

Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months

Phase 3: Patient Global Impression of Change (PGIC) score

The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change"

Day 1 of every 3 cycles: C4D1, C7D1, C10D1, etc. for the first 24 months and then Day 1 of every 4 cycles after 24 months