An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT03915951
• Recruitment Status: Active, not recruiting
• First Posted: April 16, 2019
• Results First Posted: October 30, 2023
• Last Update Posted: April 16, 2024
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer
• Interventions: Drug: encorafenib; Drug: binimetinib
• Enrollment: 98

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
Period Title: Overall Study
Started	59	39
Completed	0	0
Not Completed	59	39
Reason Not Completed
As of the PCD data-cut, 33 participants remained on-treatment.	25	8
Adverse Event	12	6
Disease progression (radiological)	17	15
Disease progression (clinical)	4	1
Patient decision	0	4
Investigator decision	0	1
Consent withdrawn	1	1
Death	0	3

Baseline Characteristics

Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Total of all reporting groups
Overall Number of Baseline Participants		59	39	98
Baseline Analysis Population Description		Baseline analysis population included all participants taking at least 1 dose of study intervention.
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	59 participants	39 participants	98 participants
		68; (47 to 83)	71; (53 to 86)	69.5; (47 to 86)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	39 participants	98 participants
	Female	33 55.9%	19 48.7%	52 53.1%
	Male	26 44.1%	20 51.3%	46 46.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	59 participants	39 participants	98 participants
	American Indian or Alaska Native	1 1.7%	0 0.0%	1 1.0%
	Asian	3 5.1%	4 10.3%	7 7.1%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 1.7%	2 5.1%	3 3.1%
	White	53 89.8%	33 84.6%	86 87.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 1.7%	0 0.0%	1 1.0%
Eastern Cooperation Oncology Group (ECOG) Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	59 participants	39 participants	98 participants
Grade 0		19 32.2%	7 17.9%	26 26.5%
Grade 1		40 67.8%	32 82.1%	72 73.5%
		[1] Measure Description: ECOG Performance Status Scoring: Grade 0: Fully active, able to carry on all predisease performance without restriction; Grade 1: restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours; Grade 3: capable of only limited self-care; confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled; cannot carry on any self-care; totally confined to bed or chair; Grade 5: dead.
Smoking Status [1]; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	59 participants	39 participants	98 participants
Current Smoking		8 13.6%	5 12.8%	13 13.3%
Former Smoking		33 55.9%	23 59.0%	56 57.1%
Never Smoking		18 30.5%	11 28.2%	29 29.6%
		[1] Measure Description: Smoking history was collected at Screening by the Investigator or qualified designee.

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)
Description	Objective Response Rate (ORR) was defined as the percentage of participants who had achieved a confirmed best overall response (Complete Response [CR] or Partial Response [PR]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated with the exact 2-sided Clopper-Pearson 95% CI.
Time Frame	From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description:	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
Overall Number of Participants Analyzed	59	39
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	74.6; (61.6 to 85.0)	46.2; (30.1 to 62.8)

2. Secondary Outcome

Title	Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment
Description	ORR was defined as the percentage of participants who had achieved a confirmed best overall response (CR or PR) per RECIST version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and the complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. ORR according to derived investigator assessment was calculated with the exact 2-sided Clopper-Pearson 95% CI.
Time Frame	From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description:	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
Overall Number of Participants Analyzed	59	39
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
	62.7; (49.1 to 75.0)	41.0; (25.6 to 57.9)

3. Secondary Outcome

Title	Duration of Response (DoR) by IRR and Investigator Assessments
Description	DoR, based on IRR and Investigator assessments was defined as the time from the date of the first documented confirmed response (CR or PR) (by IRR and by Investigator, respectively) to the earliest date of disease progression, as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1, or death due to any cause. If a participant with a CR or PR had neither progressed nor died at the time of the analysis cutoff or at the start of any new anticancer therapy, the participant was censored at the date of last adequate tumor assessment. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. DoR was calculated for participants who had achieved a confirmed overall response (CR or PR). The estimate of the DoR survival function was constructed using the Kaplan-Meier method.
Time Frame	From the date of the first confirmed documented response (CR or PR) to the earliest date of disease progression or death due to any cause (up to 36 months)

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Disease Control Rate (DCR) by IRR and Investigator Assessments
Description	DCR was defined as the percentage of participants who had achieved a confirmed overall response of CR, PR or stable disease (SD), as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1 after 24 weeks (≥168 days) from the date of first dose of study intervention. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. SD was assigned when neither sufficient shrinkage to qualify for CR or PR, nor sufficient increase to qualify for PD was observed, taking as reference the nadir. DCR was calculated along with the exact 2-sided Clopper-Pearson 95% CI.
Time Frame	After 24 Weeks (≥168 days) from the date of first dose of study intervention

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Treatment-Naive	Previously Treated
Arm/Group Description:	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
Overall Number of Participants Analyzed	59	39
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
DCR After 24 Weeks by IRR	64.4; (50.9 to 76.4)	41.0; (25.6 to 57.9)
DCR After 24 Weeks by Investigator Assessment	67.8; (54.4 to 79.4)	48.7; (32.4 to 65.2)

5. Secondary Outcome

Title	Progression-free Survival (PFS) by IRR and Investigator Assessments
Description	PFS was defined as the time from the date of first dose of study intervention to the earliest date of disease progression, as determined by IRR and Investigator review of radiographic disease assessments per RECIST version 1.1, or death due to any cause, whichever occurred first. PD was defined by a 20% or more increase in the SOD of target lesions relative to nadir (smallest SOD considering baseline and all assessments prior to the time point under evaluation), with a minimum absolute increase of 5 mm relative to nadir; PD was assigned if any non-target lesion was marked "unequivocal progression". If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. PFS (months) = [(date of event or censoring - date of first dose) +1]/30.4375. The survival distribution function for PFS was estimated using the Kaplan-Meier method.
Time Frame	From the date of first dose of study drug to the earliest date of disease progression, or death due to any cause (up to 36 months)

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Time to Response (TTR) by IRR and Investigator Assessments
Description	TTR based on IRR and Investigator assessments was defined, for participants with an objective response, as the time, in months, from the date of first dose to the first documentation of objective response (CR or PR) which was subsequently confirmed (by IRR and by Investigator, respectively). TTR was calculated for the subgroup of participants with a confirmed objective tumor response.
Time Frame	From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention and who had confirmed objective tumor response (CR or PR). Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title		Treatment-Naive	Previously Treated
Arm/Group Description:		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.
Overall Number of Participants Analyzed		59	39
Median (Full Range); Unit of Measure: Months
TTR by IRR	Number Analyzed	44 participants	18 participants
		1.86; (1.1 to 19.1)	1.74; (1.2 to 7.3)
TTR by Investigator Assessment	Number Analyzed	37 participants	16 participants
		1.84; (1.4 to 14.0)	1.81; (0.8 to 9.2)

7. Secondary Outcome

Title	Kaplan-Meier Estimates of Overall Survival (OS)
Description	OS was defined as the time from the date of first dose of study intervention to the date of death due to any cause. If a death had not been observed by the date of the analysis cutoff, OS was censored at the date of last contact. The survival distribution function for OS was estimated using the Kaplan-Meier method.
Time Frame	The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description	TEAE was a treatment-emergent adverse event that occurred during the on-treatment period. The on-treatment period was defined as the time from the first dose date of study intervention to the last dose of study drug administration date (when both drugs were permanently discontinued) +30 days or the earliest date of subsequent anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study intervention was determined by the investigator. The investigator made an assessment of intensity for each AE reported during the study according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3 events = severe AEs; Grade 4 events = life-threatening consequences, urgent intervention indicated; Grade 5 events = death related to AEs.
Time Frame	From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who received at least 1 dose of study intervention.

Arm/Group Title	Treatment-Naive	Previously Treated	Total
Arm/Group Description:	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed	59	39	98
Measure Type: Count of Participants; Unit of Measure: Participants
Participants With TEAEs	59 100.0%	38 97.4%	97 99.0%
Participants With Treatment-related TEAEs	58 98.3%	34 87.2%	92 93.9%
Participants with Maximum Grade 3 or 4 TEAEs	37 62.7%	18 46.2%	55 56.1%
Participants with Maximum Treatment-related Grade 3 or 4 TEAEs	27 45.8%	13 33.3%	40 40.8%
Participants With Grade 5 TEAEs	5 8.5%	7 17.9%	12 12.2%
Participants With Treatment-related Grade 5 TEAEs	1 1.7%	0 0.0%	1 1.0%

9. Secondary Outcome

Title	Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Hematology Laboratory Test Values Based on CTCAE Grade
Description	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time. Grade 4 was not applicable for the parameters of anemia, hemoglobin increased, leukocytosis and lymphocyte count increased as Grade 4 was not defined for these 4 parameters per CTCAE version 4.03.
Time Frame	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, End of Treatment (EOT) ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description:		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants; Unit of Measure: Participants
Anemia - Grade 3	Number Analyzed	55 participants	38 participants	93 participants
		9 16.4%	1 2.6%	10 10.8%
Hemoglobin increased - Grade 3	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	0 0.0%	0 0.0%
Leukocytosis - Grade 3	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	0 0.0%	0 0.0%
Lymphocyte count decreased - Grade 3	Number Analyzed	54 participants	37 participants	91 participants
		2 3.7%	3 8.1%	5 5.5%
Lymphocyte count decreased - Grade 4	Number Analyzed	54 participants	37 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Lymphocyte count increased - Grade 3	Number Analyzed	54 participants	37 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Neutrophil count decreased - Grade 3	Number Analyzed	54 participants	37 participants	91 participants
		1 1.9%	0 0.0%	1 1.1%
Neutrophil count decreased - Grade 4	Number Analyzed	54 participants	37 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Platelet count decreased - Grade 3	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	1 2.6%	1 1.1%
Platelet count decreased - Grade 4	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	0 0.0%	0 0.0%
White blood cell decreased - Grade 3	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	0 0.0%	0 0.0%
White blood cell decreased - Grade 4	Number Analyzed	55 participants	38 participants	93 participants
		0 0.0%	0 0.0%	0 0.0%

10. Secondary Outcome

Title	Number of Participants With Shifts From Grade ≤2 at Baseline to Grade 3 or 4 at Post-baseline in Chemistry Laboratory Test Values Based on CTCAE Grade
Description	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time. Grade 4 was not applicable for the parameters of hyperglycemia and hypoalbuminemia as Grade 4 was not defined for these 2 parameters per CTCAE version 4.03.
Time Frame	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, EOT ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description:		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants; Unit of Measure: Participants
Alanine aminotransferase increased - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		6 10.7%	2 5.3%	8 8.5%
Alanine aminotransferase increased - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Alkaline phosphatase increased - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		2 3.6%	1 2.6%	3 3.2%
Alkaline phosphatase increased - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Aspartate aminotransferase increased - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		7 12.5%	2 5.3%	9 9.6%
Aspartate aminotransferase increased - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Blood bilirubin increased - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Blood bilirubin increased - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Creatine kinase increased - Grade 3	Number Analyzed	55 participants	36 participants	91 participants
		2 3.6%	1 2.8%	3 3.3%
Creatine kinase increased - Grade 4	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Creatinine increased - Grade 3	Number Analyzed	57 participants	38 participants	95 participants
		3 5.3%	0 0.0%	3 3.2%
Creatinine increased - Grade 4	Number Analyzed	57 participants	38 participants	95 participants
		0 0.0%	0 0.0%	0 0.0%
Hypercalcemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		1 1.8%	1 2.6%	2 2.1%
Hypercalcemia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hyperglycemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		5 8.9%	1 2.6%	6 6.4%
Hyperkalemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		2 3.6%	0 0.0%	2 2.1%
Hyperkalemia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypermagnesemia - Grade 3	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	1 2.8%	1 1.1%
Hypermagnesemia - Grade 4	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Hypernatremia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypernatremia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypoalbuminemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypocalcemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypocalcemia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		2 3.6%	0 0.0%	2 2.1%
Hypoglycemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypoglycemia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypokalemia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	1 2.6%	1 1.1%
Hypokalemia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypomagnesemia - Grade 3	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Hypomagnesemia - Grade 4	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Hyponatremia - Grade 3	Number Analyzed	56 participants	38 participants	94 participants
		7 12.5%	2 5.3%	9 9.6%
Hyponatremia - Grade 4	Number Analyzed	56 participants	38 participants	94 participants
		0 0.0%	0 0.0%	0 0.0%
Hypophosphatemia - Grade 3	Number Analyzed	55 participants	36 participants	91 participants
		1 1.8%	0 0.0%	1 1.1%
Hypophosphatemia - Grade 4	Number Analyzed	55 participants	36 participants	91 participants
		0 0.0%	0 0.0%	0 0.0%
Lipase increased - Grade 3	Number Analyzed	56 participants	36 participants	92 participants
		8 14.3%	3 8.3%	11 12.0%
Lipase increased - Grade 4	Number Analyzed	56 participants	36 participants	92 participants
		2 3.6%	0 0.0%	2 2.2%
Serum amylase increased - Grade 3	Number Analyzed	56 participants	36 participants	92 participants
		1 1.8%	0 0.0%	1 1.1%
Serum amylase increased - Grade 4	Number Analyzed	56 participants	36 participants	92 participants
		0 0.0%	0 0.0%	0 0.0%

11. Secondary Outcome

Title	Number of Participants With Notable Abnormal Vital Signs
Description	Vital sign measurements were taken before blood collection for laboratory tests or at least 30 minutes after blood collection for laboratory tests, and were measured per institutional standards. Vital sign assessments included temperature, pulse rate, respiratory rate, and blood pressure (assessed in a recumbent, semi recumbent, or sitting position). The criteria of notably abnormal vital signs are listed below: Systolic blood pressure (mmHg): high: ≥160 mmHg with increase from baseline of ≥20 mmHg; low: ≤90 mmHg with decrease from baseline of ≥20 mmHg. Diastolic blood pressure (mmHg): high: ≥100 mmHg with increase from baseline of ≥15 mmHg; low: ≤50 mmHg with decrease from baseline of ≥15 mmHg. Pulse rate (bpm): high: ≥120 bpm with increase from baseline of ≥15 bpm; low: ≤50 bpm with decrease from baseline of ≥15 bpm. Weight (kg): high: ≥10% increase from baseline; low: ≥20% decrease from baseline. Temperature (°C): high: ≥37.5 °C; low: ≤36 °C.
Time Frame	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days of Subsequent Cycles, EOT ±3 Days, and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)

Outcome Measure Data

Analysis Population Description

Analysis population included all participants who received at least 1 dose of study intervention and had baseline and post-baseline vital sign values. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description:		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants; Unit of Measure: Participants
Systolic blood pressure - high	Number Analyzed	58 participants	38 participants	96 participants
		10 17.2%	4 10.5%	14 14.6%
Systolic blood pressure - low	Number Analyzed	58 participants	38 participants	96 participants
		5 8.6%	2 5.3%	7 7.3%
Diastolic blood pressure - high	Number Analyzed	58 participants	38 participants	96 participants
		5 8.6%	1 2.6%	6 6.3%
Diastolic blood pressure - low	Number Analyzed	58 participants	38 participants	96 participants
		2 3.4%	2 5.3%	4 4.2%
Pulse rate - high	Number Analyzed	58 participants	38 participants	96 participants
		2 3.4%	6 15.8%	8 8.3%
Pulse rate - low	Number Analyzed	58 participants	38 participants	96 participants
		1 1.7%	1 2.6%	2 2.1%
Weight - high	Number Analyzed	57 participants	38 participants	95 participants
		17 29.8%	4 10.5%	21 22.1%
Weight - low	Number Analyzed	57 participants	38 participants	95 participants
		1 1.8%	0 0.0%	1 1.1%
Temperature - high	Number Analyzed	58 participants	38 participants	96 participants
		8 13.8%	3 7.9%	11 11.5%
Temperature - low	Number Analyzed	58 participants	38 participants	96 participants
		25 43.1%	10 26.3%	35 36.5%

12. Secondary Outcome

Title	Number of Participants With Notable ECG (QTcF) Values
Description	The QTcF increase from baseline >30/60 msec and new QTcF >450/480/500 msec were defined as clinically notable ECG criteria. Triplicate ECG measurements were obtained. For new abnormal post-baseline values, the table below presents the number of participants with both non-missing baseline and post-baseline values, and baseline values not meeting the criteria. For abnormal changes from baseline, the table below presents the number of participants with both non-missing baseline and post-baseline evaluations. Baseline was defined as the average of the machine-read triplicate ECG measurements taken pre-dose on Day 1. Change from baseline was post-baseline - baseline values.
Time Frame	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all participants who received at least 1 dose of study intervention. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title		Treatment-Naive	Previously Treated	Total
Arm/Group Description:		Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed		59	39	98
Measure Type: Count of Participants; Unit of Measure: Participants
New QTcF >450 msec	Number Analyzed	54 participants	31 participants	85 participants
		12 22.2%	7 22.6%	19 22.4%
New QTcF >480 msec	Number Analyzed	57 participants	37 participants	94 participants
		5 8.8%	5 13.5%	10 10.6%
New QTcF >500 msec	Number Analyzed	58 participants	37 participants	95 participants
		1 1.7%	1 2.7%	2 2.1%
QTcF Increase from baseline >30 msec	Number Analyzed	58 participants	38 participants	96 participants
		20 34.5%	9 23.7%	29 30.2%
QTcF Increase from baseline >60 msec	Number Analyzed	58 participants	38 participants	96 participants
		3 5.2%	4 10.5%	7 7.3%

13. Secondary Outcome

Title	Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade
Description	Cardiac ejection fraction was assessed by transthoracic echocardiogram (ECHO) or multigated acquisition (MUGA). Participants who developed signs/symptoms of congestive heart failure (CHF) at any point during the study were required to have an evaluation of LVEF measurements by ECHO or MUGA and were monitored per institutional guidelines. Participants were considered as having a LVEF abnormality if the worst post-value was CTCAE Grade 2, 3 or 4 according to the following classification: Grade 0: Non-missing value below Grade 2. Grade 2: LVEF between 40% and 50%, inclusive, or absolute change from baseline between -10% and < -20%. Grade 3: LVEF between 20% and 39%, inclusive, or absolute change from baseline ≤ -20%. Grade 4: LVEF lower than 20%. Baseline was defined as the last available and valid assessment before or on the start date of study intervention.
Time Frame	Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

Outcome Measure Data

Analysis Population Description

Analysis Population included all participants who received at least 1 dose of study intervention and had both baseline and post-baseline LVEF values. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.

Arm/Group Title	Treatment-Naive	Previously Treated	Total
Arm/Group Description:	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
Overall Number of Participants Analyzed	56	33	89
Measure Type: Count of Participants; Unit of Measure: Participants
Grade 0	45 80.4%	24 72.7%	69 77.5%
Grade 2	11 19.6%	7 21.2%	18 20.2%
Grade 3	0 0.0%	2 6.1%	2 2.2%
Grade 4	0 0.0%	0 0.0%	0 0.0%

Adverse Events

Time Frame	From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months)
Adverse Event Reporting Description	Same event may appear as both an AE and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another participant, or 1 participant may have experienced both serious and non-serious event during the study. Safety analysis set included all participants who received at least 1 dose of study intervention.
Arm/Group Title	Treatment-Naive	Previously Treated	Total
Arm/Group Description	Treatment-naïve participants with BRAF V600E-mutant metastatic NSCLC were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Patients who had received 1) first-line treatment with standard platinum-based chemotherapy, or 2) first-line treatment with an anti-PD-1/PD-L1 inhibitor given alone, or in combination with platinum-based chemotherapy, or in combination with immunotherapy (eg, ipilimumab) with or without platinum-based chemotherapy were enrolled to receive encorafenib 450 mg QD and binimetinib 45 mg BID was to be administered in 28-day (±3 days) cycles and continued until the participants met the protocol-defined criteria for treatment withdrawal.	Sum of all participants in the Study C4221008 (ARRAY-818-202)
All-Cause Mortality
	Treatment-Naive	Previously Treated	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	5/59 (8.47%)	7/39 (17.95%)	12/98 (12.24%)
Serious Adverse Events
	Treatment-Naive	Previously Treated	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	25/59 (42.37%)	17/39 (43.59%)	42/98 (42.86%)
Blood and lymphatic system disorders
Anaemia * 1	3/59 (5.08%)	0/39 (0.00%)	3/98 (3.06%)
Disseminated intravascular coagulation * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Cardiac disorders
Myocardial infarction * 1	1/59 (1.69%)	1/39 (2.56%)	2/98 (2.04%)
Atrial fibrillation * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Pericardial effusion * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Supraventricular tachyarrhythmia * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Tachycardia * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Eye disorders
Retinal detachment * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Gastrointestinal disorders
Colitis * 1	4/59 (6.78%)	0/39 (0.00%)	4/98 (4.08%)
Constipation * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Diarrhoea * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Duodenal ulcer * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Gastrointestinal haemorrhage * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Nausea * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Small intestinal haemorrhage * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Upper gastrointestinal haemorrhage * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
General disorders
Disease progression * 1	2/59 (3.39%)	4/39 (10.26%)	6/98 (6.12%)
Oedema peripheral * 1	2/59 (3.39%)	0/39 (0.00%)	2/98 (2.04%)
Asthenia * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Hepatobiliary disorders
Cholecystitis * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Cholelithiasis * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Infections and infestations
Device related infection * 1	1/59 (1.69%)	1/39 (2.56%)	2/98 (2.04%)
Pneumonia * 1	2/59 (3.39%)	0/39 (0.00%)	2/98 (2.04%)
COVID-19 * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
COVID-19 pneumonia * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Cellulitis * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Clostridium difficile colitis * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Empyema * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Herpes zoster * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Ophthalmic herpes zoster * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Pneumonia mycoplasmal * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Respiratory tract infection * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Urinary tract infection * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Urosepsis * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Injury, poisoning and procedural complications
Femur fracture * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Head injury * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Hip fracture * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Upper limb fracture * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Investigations
Blood creatinine increased * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Metabolism and nutrition disorders
Hyponatraemia * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Musculoskeletal and connective tissue disorders
Back pain * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression * 1	2/59 (3.39%)	2/39 (5.13%)	4/98 (4.08%)
Squamous cell carcinoma of skin * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Nervous system disorders
Cerebrovascular accident * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Cognitive disorder * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Haemorrhage intracranial * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Hemiparesis * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Presyncope * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Seizure * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Psychiatric disorders
Confusional state * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Hallucination, auditory * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Renal and urinary disorders
Acute kidney injury * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	0/59 (0.00%)	3/39 (7.69%)	3/98 (3.06%)
Haemothorax * 1	2/59 (3.39%)	0/39 (0.00%)	2/98 (2.04%)
Pleural effusion * 1	1/59 (1.69%)	1/39 (2.56%)	2/98 (2.04%)
Chronic respiratory failure * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Haemoptysis * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Pneumothorax * 1	0/59 (0.00%)	1/39 (2.56%)	1/98 (1.02%)
Vascular disorders
Hypertension * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
Peripheral embolism * 1	1/59 (1.69%)	0/39 (0.00%)	1/98 (1.02%)
1 Term from vocabulary, MedDRA version 25.0; * Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment-Naive	Previously Treated	Total
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	59/59 (100.00%)	38/39 (97.44%)	97/98 (98.98%)
Blood and lymphatic system disorders
Anaemia * 1	20/59 (33.90%)	10/39 (25.64%)	30/98 (30.61%)
Eye disorders
Vision blurred * 1	14/59 (23.73%)	6/39 (15.38%)	20/98 (20.41%)
Gastrointestinal disorders
Nausea * 1	37/59 (62.71%)	19/39 (48.72%)	56/98 (57.14%)
Diarrhoea * 1	29/59 (49.15%)	20/39 (51.28%)	49/98 (50.00%)
Vomiting * 1	23/59 (38.98%)	13/39 (33.33%)	36/98 (36.73%)
Constipation * 1	18/59 (30.51%)	8/39 (20.51%)	26/98 (26.53%)
Abdominal pain * 1	14/59 (23.73%)	6/39 (15.38%)	20/98 (20.41%)
Abdominal pain upper * 1	4/59 (6.78%)	4/39 (10.26%)	8/98 (8.16%)
General disorders
Fatigue * 1	29/59 (49.15%)	16/39 (41.03%)	45/98 (45.92%)
Pyrexia * 1	16/59 (27.12%)	6/39 (15.38%)	22/98 (22.45%)
Oedema peripheral * 1	12/59 (20.34%)	8/39 (20.51%)	20/98 (20.41%)
Asthenia * 1	7/59 (11.86%)	9/39 (23.08%)	16/98 (16.33%)
Non-cardiac chest pain * 1	6/59 (10.17%)	2/39 (5.13%)	8/98 (8.16%)
Chills * 1	3/59 (5.08%)	3/39 (7.69%)	6/98 (6.12%)
Malaise * 1	5/59 (8.47%)	1/39 (2.56%)	6/98 (6.12%)
Infections and infestations
COVID-19 * 1	5/59 (8.47%)	2/39 (5.13%)	7/98 (7.14%)
Investigations
Aspartate aminotransferase increased * 1	11/59 (18.64%)	4/39 (10.26%)	15/98 (15.31%)
Blood creatine phosphokinase increased * 1	10/59 (16.95%)	5/39 (12.82%)	15/98 (15.31%)
Blood creatinine increased * 1	8/59 (13.56%)	7/39 (17.95%)	15/98 (15.31%)
Lipase increased * 1	11/59 (18.64%)	4/39 (10.26%)	15/98 (15.31%)
Alanine aminotransferase increased * 1	10/59 (16.95%)	3/39 (7.69%)	13/98 (13.27%)
Blood alkaline phosphatase increased * 1	9/59 (15.25%)	2/39 (5.13%)	11/98 (11.22%)
Weight increased * 1	10/59 (16.95%)	1/39 (2.56%)	11/98 (11.22%)
Ejection fraction decreased * 1	4/59 (6.78%)	4/39 (10.26%)	8/98 (8.16%)
SARS-CoV-2 test positive * 1	4/59 (6.78%)	4/39 (10.26%)	8/98 (8.16%)
Weight decreased * 1	6/59 (10.17%)	1/39 (2.56%)	7/98 (7.14%)
Amylase increased * 1	4/59 (6.78%)	2/39 (5.13%)	6/98 (6.12%)
Platelet count decreased * 1	2/59 (3.39%)	4/39 (10.26%)	6/98 (6.12%)
Metabolism and nutrition disorders
Decreased appetite * 1	12/59 (20.34%)	2/39 (5.13%)	14/98 (14.29%)
Hyponatraemia * 1	7/59 (11.86%)	5/39 (12.82%)	12/98 (12.24%)
Hyperglycaemia * 1	4/59 (6.78%)	3/39 (7.69%)	7/98 (7.14%)
Hyperkalaemia * 1	6/59 (10.17%)	1/39 (2.56%)	7/98 (7.14%)
Hypoalbuminaemia * 1	4/59 (6.78%)	3/39 (7.69%)	7/98 (7.14%)
Dehydration * 1	2/59 (3.39%)	3/39 (7.69%)	5/98 (5.10%)
Musculoskeletal and connective tissue disorders
Back pain * 1	11/59 (18.64%)	8/39 (20.51%)	19/98 (19.39%)
Arthralgia * 1	9/59 (15.25%)	6/39 (15.38%)	15/98 (15.31%)
Pain in extremity * 1	6/59 (10.17%)	7/39 (17.95%)	13/98 (13.27%)
Muscle spasms * 1	10/59 (16.95%)	2/39 (5.13%)	12/98 (12.24%)
Myalgia * 1	6/59 (10.17%)	4/39 (10.26%)	10/98 (10.20%)
Muscular weakness * 1	5/59 (8.47%)	2/39 (5.13%)	7/98 (7.14%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis * 1	5/59 (8.47%)	2/39 (5.13%)	7/98 (7.14%)
Nervous system disorders
Dizziness * 1	10/59 (16.95%)	6/39 (15.38%)	16/98 (16.33%)
Headache * 1	6/59 (10.17%)	4/39 (10.26%)	10/98 (10.20%)
Dysgeusia * 1	5/59 (8.47%)	3/39 (7.69%)	8/98 (8.16%)
Paraesthesia * 1	5/59 (8.47%)	0/39 (0.00%)	5/98 (5.10%)
Psychiatric disorders
Insomnia * 1	7/59 (11.86%)	3/39 (7.69%)	10/98 (10.20%)
Renal and urinary disorders
Pollakiuria * 1	6/59 (10.17%)	0/39 (0.00%)	6/98 (6.12%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea * 1	16/59 (27.12%)	7/39 (17.95%)	23/98 (23.47%)
Cough * 1	11/59 (18.64%)	6/39 (15.38%)	17/98 (17.35%)
Productive cough * 1	8/59 (13.56%)	3/39 (7.69%)	11/98 (11.22%)
Skin and subcutaneous tissue disorders
Pruritus * 1	7/59 (11.86%)	8/39 (20.51%)	15/98 (15.31%)
Dry skin * 1	11/59 (18.64%)	2/39 (5.13%)	13/98 (13.27%)
Alopecia * 1	9/59 (15.25%)	3/39 (7.69%)	12/98 (12.24%)
Rash * 1	6/59 (10.17%)	5/39 (12.82%)	11/98 (11.22%)
Rash maculo-papular * 1	5/59 (8.47%)	3/39 (7.69%)	8/98 (8.16%)
Hair texture abnormal * 1	5/59 (8.47%)	1/39 (2.56%)	6/98 (6.12%)
Hyperkeratosis * 1	4/59 (6.78%)	1/39 (2.56%)	5/98 (5.10%)
Vascular disorders
Hypertension * 1	8/59 (13.56%)	2/39 (5.13%)	10/98 (10.20%)
1 Term from vocabulary, MedDRA version 25.0; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

Results Point of Contact

• Name/Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.
• Phone: 1-800-718-1021
• EMail: ClinicalTrials.gov_Inquiries@pfizer.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Riely GJ, Ahn MJ, Felip E, Ramalingam SS, Smit EF, Tsao AS, Alcasid A, Usari T, Wissel PS, Wilner KD, Johnson BE. Encorafenib plus binimetinib in patients with BRAFV600-mutant non-small cell lung cancer: phase II PHAROS study design. Future Oncol. 2022 Mar;18(7):781-791. doi: 10.2217/fon-2021-1250. Epub 2021 Dec 17.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03915951
• Other Study ID Numbers: ARRAY-818-202; C4221008 ( Other Identifier: Alias Study Number ); 2019-000417-37 ( EudraCT Number )
• First Submitted: April 12, 2019
• First Posted: April 16, 2019
• Results First Submitted: September 18, 2023
• Results First Posted: October 30, 2023
• Last Update Posted: April 16, 2024