Trial Outcomes & Findings for An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer (NCT NCT03915951)

Last Updated: 2025-11-17

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

98 participants

Primary outcome timeframe

From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)

Results posted on

2025-11-17

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment-Naive 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.	Previously Treated 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 Study STARTED	59	39
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	59	39

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment-Naive 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.	Previously Treated 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 Study As of the PCD data-cut, 33 participants remained on-treatment.	25	8
Overall Study Adverse Event	12	6
Overall Study Disease progression (radiological)	17	15
Overall Study Disease progression (clinical)	4	1
Overall Study Patient decision	0	4
Overall Study Investigator decision	0	1
Overall Study Consent withdrawn	1	1
Overall Study Death	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Total of all reporting groups
Age, Continuous	68 Years n=202 Participants	71 Years n=283 Participants	69.5 Years n=120 Participants
Sex: Female, Male Female	33 Participants n=202 Participants	19 Participants n=283 Participants	52 Participants n=120 Participants
Sex: Female, Male Male	26 Participants n=202 Participants	20 Participants n=283 Participants	46 Participants n=120 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=202 Participants	0 Participants n=283 Participants	1 Participants n=120 Participants
Race (NIH/OMB) Asian	3 Participants n=202 Participants	4 Participants n=283 Participants	7 Participants n=120 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=202 Participants	0 Participants n=283 Participants	0 Participants n=120 Participants
Race (NIH/OMB) Black or African American	1 Participants n=202 Participants	2 Participants n=283 Participants	3 Participants n=120 Participants
Race (NIH/OMB) White	53 Participants n=202 Participants	33 Participants n=283 Participants	86 Participants n=120 Participants
Race (NIH/OMB) More than one race	0 Participants n=202 Participants	0 Participants n=283 Participants	0 Participants n=120 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=202 Participants	0 Participants n=283 Participants	1 Participants n=120 Participants
Eastern Cooperation Oncology Group (ECOG) Performance Status Grade 0	19 Participants n=202 Participants	7 Participants n=283 Participants	26 Participants n=120 Participants
Eastern Cooperation Oncology Group (ECOG) Performance Status Grade 1	40 Participants n=202 Participants	32 Participants n=283 Participants	72 Participants n=120 Participants
Smoking Status Current Smoking	8 Participants n=202 Participants	5 Participants n=283 Participants	13 Participants n=120 Participants
Smoking Status Former Smoking	33 Participants n=202 Participants	23 Participants n=283 Participants	56 Participants n=120 Participants
Smoking Status Never Smoking	18 Participants n=202 Participants	11 Participants n=283 Participants	29 Participants n=120 Participants

PRIMARY outcome

Timeframe: From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)

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

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 Sum of all participants in the Study C4221008 (ARRAY-818-202)
Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)	74.6 Percentage of Participants Interval 61.6 to 85.0	46.2 Percentage of Participants Interval 30.1 to 62.8	—

SECONDARY outcome

Timeframe: From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)

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

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 Sum of all participants in the Study C4221008 (ARRAY-818-202)
Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment	62.7 Percentage of Participants Interval 49.1 to 75.0	41.0 Percentage of Participants Interval 25.6 to 57.9	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: After 24 Weeks (≥168 days) from the date of first dose of study intervention

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

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 Sum of all participants in the Study C4221008 (ARRAY-818-202)
Disease Control Rate (DCR) by IRR and Investigator Assessments DCR After 24 Weeks by IRR	64.4 Percentage of Participants Interval 50.9 to 76.4	41.0 Percentage of Participants Interval 25.6 to 57.9	—
Disease Control Rate (DCR) by IRR and Investigator Assessments DCR After 24 Weeks by Investigator Assessment	67.8 Percentage of Participants Interval 54.4 to 79.4	48.7 Percentage of Participants Interval 32.4 to 65.2	—

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 Sum of all participants in the Study C4221008 (ARRAY-818-202)
Time to Response (TTR) by IRR and Investigator Assessments TTR by IRR	1.86 Months Interval 1.1 to 19.1	1.74 Months Interval 1.2 to 7.3	—
Time to Response (TTR) by IRR and Investigator Assessments TTR by Investigator Assessment	1.84 Months Interval 1.4 to 14.0	1.81 Months Interval 0.8 to 9.2	—

SECONDARY outcome

Timeframe: The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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)

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

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants With Treatment-related TEAEs	58 Participants	34 Participants	92 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants with Maximum Treatment-related Grade 3 or 4 TEAEs	27 Participants	13 Participants	40 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants With TEAEs	59 Participants	38 Participants	97 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants with Maximum Grade 3 or 4 TEAEs	37 Participants	18 Participants	55 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants With Grade 5 TEAEs	5 Participants	7 Participants	12 Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Participants With Treatment-related Grade 5 TEAEs	1 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
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 Hemoglobin increased - Grade 3	0 Participants	0 Participants	0 Participants
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 Leukocytosis - Grade 3	0 Participants	0 Participants	0 Participants
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 Anemia - Grade 3	9 Participants	1 Participants	10 Participants
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 Lymphocyte count decreased - Grade 3	2 Participants	3 Participants	5 Participants
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 Lymphocyte count decreased - Grade 4	0 Participants	0 Participants	0 Participants
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 Lymphocyte count increased - Grade 3	0 Participants	0 Participants	0 Participants
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 Neutrophil count decreased - Grade 3	1 Participants	0 Participants	1 Participants
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 Neutrophil count decreased - Grade 4	0 Participants	0 Participants	0 Participants
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 Platelet count decreased - Grade 3	0 Participants	1 Participants	1 Participants
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 Platelet count decreased - Grade 4	0 Participants	0 Participants	0 Participants
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 White blood cell decreased - Grade 3	0 Participants	0 Participants	0 Participants
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 White blood cell decreased - Grade 4	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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)

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
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 Hypomagnesemia - Grade 3	0 Participants	0 Participants	0 Participants
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 Alanine aminotransferase increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Alkaline phosphatase increased - Grade 3	2 Participants	1 Participants	3 Participants
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 Hypercalcemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypoglycemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypokalemia - Grade 3	0 Participants	1 Participants	1 Participants
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 Hypomagnesemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypophosphatemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Lipase increased - Grade 3	8 Participants	3 Participants	11 Participants
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 Alanine aminotransferase increased - Grade 3	6 Participants	2 Participants	8 Participants
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 Alkaline phosphatase increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Aspartate aminotransferase increased - Grade 3	7 Participants	2 Participants	9 Participants
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 Aspartate aminotransferase increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Blood bilirubin increased - Grade 3	0 Participants	0 Participants	0 Participants
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 Blood bilirubin increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Creatine kinase increased - Grade 3	2 Participants	1 Participants	3 Participants
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 Creatine kinase increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Creatinine increased - Grade 3	3 Participants	0 Participants	3 Participants
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 Creatinine increased - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypercalcemia - Grade 3	1 Participants	1 Participants	2 Participants
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 Hyperglycemia - Grade 3	5 Participants	1 Participants	6 Participants
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 Hyperkalemia - Grade 3	2 Participants	0 Participants	2 Participants
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 Hyperkalemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypermagnesemia - Grade 3	0 Participants	1 Participants	1 Participants
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 Hypermagnesemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypernatremia - Grade 3	0 Participants	0 Participants	0 Participants
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 Hypernatremia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypoalbuminemia - Grade 3	0 Participants	0 Participants	0 Participants
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 Hypocalcemia - Grade 3	0 Participants	0 Participants	0 Participants
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 Hypocalcemia - Grade 4	2 Participants	0 Participants	2 Participants
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 Hypoglycemia - Grade 3	0 Participants	0 Participants	0 Participants
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 Hypokalemia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hyponatremia - Grade 3	7 Participants	2 Participants	9 Participants
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 Hyponatremia - Grade 4	0 Participants	0 Participants	0 Participants
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 Hypophosphatemia - Grade 3	1 Participants	0 Participants	1 Participants
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 Lipase increased - Grade 4	2 Participants	0 Participants	2 Participants
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 Serum amylase increased - Grade 3	1 Participants	0 Participants	1 Participants
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 Serum amylase increased - Grade 4	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
Number of Participants With Notable Abnormal Vital Signs Systolic blood pressure - high	10 Participants	4 Participants	14 Participants
Number of Participants With Notable Abnormal Vital Signs Pulse rate - low	1 Participants	1 Participants	2 Participants
Number of Participants With Notable Abnormal Vital Signs Systolic blood pressure - low	5 Participants	2 Participants	7 Participants
Number of Participants With Notable Abnormal Vital Signs Diastolic blood pressure - high	5 Participants	1 Participants	6 Participants
Number of Participants With Notable Abnormal Vital Signs Diastolic blood pressure - low	2 Participants	2 Participants	4 Participants
Number of Participants With Notable Abnormal Vital Signs Pulse rate - high	2 Participants	6 Participants	8 Participants
Number of Participants With Notable Abnormal Vital Signs Weight - high	17 Participants	4 Participants	21 Participants
Number of Participants With Notable Abnormal Vital Signs Weight - low	1 Participants	0 Participants	1 Participants
Number of Participants With Notable Abnormal Vital Signs Temperature - high	8 Participants	3 Participants	11 Participants
Number of Participants With Notable Abnormal Vital Signs Temperature - low	25 Participants	10 Participants	35 Participants

SECONDARY outcome

Timeframe: Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=59 Participants 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.	Previously Treated n=39 Participants 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 n=98 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
Number of Participants With Notable ECG (QTcF) Values New QTcF >450 msec	12 Participants	7 Participants	19 Participants
Number of Participants With Notable ECG (QTcF) Values New QTcF >480 msec	5 Participants	5 Participants	10 Participants
Number of Participants With Notable ECG (QTcF) Values New QTcF >500 msec	1 Participants	1 Participants	2 Participants
Number of Participants With Notable ECG (QTcF) Values QTcF Increase from baseline >30 msec	20 Participants	9 Participants	29 Participants
Number of Participants With Notable ECG (QTcF) Values QTcF Increase from baseline >60 msec	3 Participants	4 Participants	7 Participants

SECONDARY outcome

Timeframe: Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Treatment-Naive n=56 Participants 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.	Previously Treated n=33 Participants 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 n=89 Participants Sum of all participants in the Study C4221008 (ARRAY-818-202)
Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade Grade 0	45 Participants	24 Participants	69 Participants
Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade Grade 2	11 Participants	7 Participants	18 Participants
Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade Grade 3	0 Participants	2 Participants	2 Participants
Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade Grade 4	0 Participants	0 Participants	0 Participants

Adverse Events

Treatment-Naive

Serious events: 25 serious events

Other events: 59 other events

Deaths: 5 deaths

Previously Treated

Serious events: 17 serious events

Other events: 38 other events

Deaths: 7 deaths

Total

Serious events: 42 serious events

Other events: 97 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER