Study Comparing the Efficacy of MEK162 Versus Dacarbazine in Unresectable or Metastatic NRAS Mutation-positive Melanoma

• ClinicalTrials.gov Identifier: NCT01763164
• Recruitment Status: Completed
• First Posted: January 8, 2013
• Results First Posted: March 22, 2021
• Last Update Posted: March 22, 2021
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic or Unresectable Cutaneous Melanoma
• Interventions: Drug: MEK162; Drug: Dacarbazine
• Enrollment: 402

Participant Flow

Recruitment Details	Participants randomized were with previously untreated, advanced unresectable or metastatic Neuroblastoma RAS viral oncogene homolog (NRAS) mutation-positive melanoma as confirmed by central assessment.
Pre-assignment Details

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Period Title: Treatment Phase
Started	269	133
Treated/Safety Set	269	114
Full Analysis Set	269	133
Completed	0	0
Not Completed	269	133
Reason Not Completed
Participant/Guardian decision	26	14
Protocol Violation	1	1
Progressive Disease	142	76
Physician Decision	24	13
Death	10	1
Adverse Event	66	8
Randomized but not Treated	0	19
Other	0	1
Period Title: Follow up Phase
Started	200 [1]	78 [1]
Completed	3	3
Not Completed	197	75
Reason Not Completed
New therapy for study indication	12	3
Death	21	4
Subject/guardian decision	9	2
Progressive disease	127	62
Physician Decision	10	3
Lost to Follow-up	1	0
Adverse Event	17	1
[1] Participants were followed up after completion or discontinuation of treatment.

Baseline Characteristics

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine	Total
Arm/Group Description		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Total of all reporting groups
Overall Number of Baseline Participants		269	133	402
Baseline Analysis Population Description		Full analysis set (FAS) included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	269 participants	133 participants	402 participants
		63.6 (12.28)	60.6 (13.35)	62.6 (12.71)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	269 participants	133 participants	402 participants
	Female	103 38.3%	48 36.1%	151 37.6%
	Male	166 61.7%	85 63.9%	251 62.4%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Description	PFS: time from randomization to first documented PD or death due to any cause, whichever occurred first. RECIST 1.1, PD: >=20% increase in sum of diameter of target lesions (TLs) taking as reference the smallest sum on study (including baseline sum), sum must also be an absolute increase of >=5 mm; unequivocal progression of existing non-TLs; appearance of >=1 lesion. Complete response (CR): disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs. Partial response (PR): >=30% decrease in sum of diameter of all TLs, referring baseline sum of diameters. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor increase in lesions qualified for PD referring smallest sum diameter. With no event at time of analysis cut-off or at start of any new anti-neoplastic therapy, PFS censored at date of last adequate tumor assessment of CR, PR or SD.
Time Frame	From the date of randomization to the date of the first documented PD or death, whichever occurred first (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	133
Median (95% Confidence Interval); Unit of Measure: Months
	2.83; (2.76 to 3.55)	1.51; (1.48 to 1.71)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	Hazard ratio was obtained from the stratified unadjusted Cox model. P-value was obtained from the one-sided stratified log-rank test.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	< 0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.47 to 0.80
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival was defined as the time from the date of randomization to the date of death due to any cause. If a participant was not known to have died, overall survival was censored at the date of last known date participant alive.
Time Frame	From the date of randomization to the date of death (maximum up to 107 weeks for binimetinib arm; maximum up to 88 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	133
Median (95% Confidence Interval); Unit of Measure: Months
	10.97; (8.94 to 13.60)	10.09; (7.03 to 16.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	Hazard ratio was obtained from the stratified unadjusted Cox model. P-value was obtained from the one-sided stratified log rank test.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.499
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.33
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Overall Response Rate (ORR)
Description	ORR: percentage of participants with best overall response (BOR) of CR or PR. BOR: best response recorded from start of treatment until CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters. ORR is reported for confirmed and unconfirmed responses. Confirmed CR or PR = at least 2 determinations of CR or PR at least 4 weeks apart before PD. PD: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion.
Time Frame	From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	133
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of Participants
Confirmed ORR	15.2; (11.2 to 20.1)	6.8; (3.1 to 12.5)
Confirmed + Unconfirmed: ORR	22.7; (17.8 to 28.2)	9.8; (5.3 to 16.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	Confirmed ORR: The p-value (2-sided) was computed from stratified Cochran-Mantel-Haenszel chi-square test statistic.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.015
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	Confirmed ORR + Unconfirmed ORR: The p-value (2-sided) was computed from stratified Cochran-Mantel-Haenszel chi-square test statistic.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.002
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]

4. Secondary Outcome

Title	Time to Response (TTR)
Description	TTR: time between date of randomization until first documented response of CR or PR. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: >=20% increase in sum of diameter of all measured TLs taking as reference smallest sum of diameter of all TLs recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-TLs. Appearance of >=1 new lesion. Participants who did not achieve PR or CR censored at last adequate tumor assessment date when they did not have PFS event (time from date of randomization to date of first documented PD or death due to any cause, whichever occur first) or at maximum follow-up when they had PFS event.
Time Frame	From date of randomization until first documented response of CR or PR (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all randomized participants and who had at least once CR or PR.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	61	13
Median (95% Confidence Interval); Unit of Measure: Months
	1.45; (1.45 to 1.48)	2.79; (1.22 to 3.38)

5. Secondary Outcome

Title	Duration of Objective Response (DOR)
Description	DOR: time from date of first documented response (CR or PR) to first documented progression or death due to underlying cancer. RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter (dia) of all TLs, referring baseline sum of dia; c) PD: >=20% increase in sum of diameter of all measured target lesions taking as reference smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion. If a participant with a CR or PR had no PD or death due to underlying cancer, participants was censored at date of last adequate tumor assessment.
Time Frame	From the date of first documented response (CR or PR) to the first documented progression or death (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

Analysis population consisted of all randomized participants and who had confirmed responses (CR or PR).

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	41	9
Median (95% Confidence Interval); Unit of Measure: Months
	6.87; (4.21 to 11.07)	NA [1]; (4.14 to NA)

[1]

Median and 95% CI upper limit was not estimable due to very less number of participants with event.

6. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	DCR was calculated as the percentage of participants with a BOR of CR, PR, SD RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (TLs) or non-pathological (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters; c) SD: neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD taking as reference the smallest sum diameters; d) PD: >=20% increase in sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline, sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non-target lesions. Appearance of at least 1 new lesion.
Time Frame	From date of randomization until first documented response of CR, PR, SD or non-CR/non-PD (maximum up to 77 weeks for binimetinib arm; maximum up to 61 weeks for dacarbazine arm)

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	133
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	58.4; (52.2 to 64.3)	24.8; (17.7 to 33.0)

7. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE was defined as one of the following: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AE was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs.
Time Frame	From baseline up to 219.4 weeks for binimetinib arm; From baseline up to 123.9 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	114
Measure Type: Count of Participants; Unit of Measure: Participants
AEs	269 100.0%	104 91.2%
SAEs	95 35.3%	26 22.8%

8. Secondary Outcome

Title	Number of Participants With Clinically Notable Hematology Shifts Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE) Grade, Version 4.03
Description	Clinically notable shifts are defined as worsening by at least 2 grades or to >= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	114
Measure Type: Count of Participants; Unit of Measure: Participants
Activated partial thromboplastin time prolonged	7 2.6%	2 1.8%
Hemoglobin decreased	17 6.3%	13 11.4%
Prothrombin international normalized ratio increased	9 3.3%	0 0.0%
Lymphocytes increased	20 7.4%	0 0.0%
Lymphocytes decreased	35 13.0%	19 16.7%
Neutrophils decreased	8 3.0%	21 18.4%
Platelets decreased	3 1.1%	17 14.9%
Leukocytes increased	0 0.0%	0 0.0%
Leukocytes decreased	6 2.2%	26 22.8%

9. Secondary Outcome

Title	Number of Participants With Clinically Notable Clinical Chemistry/Biochemistry Shifts Based on NCI-CTCAE Grade, Version 4.03
Description	Clinically notable shifts are defined as worsening by at least 2 grades or to >= grade 3. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	114
Measure Type: Count of Participants; Unit of Measure: Participants
Albumin decreased	27 10.0%	5 4.4%
Alkaline phosphatase	8 3.0%	2 1.8%
Alanine aminotransferase	14 5.2%	4 3.5%
Aspartate aminotransferase	20 7.4%	1 0.9%
Bilirubin	1 0.4%	1 0.9%
Corrected Calcium increased	2 0.7%	4 3.5%
Corrected Calcium decreased	2 0.7%	0 0.0%
Creatinine	9 3.3%	2 1.8%
Gamma-glutamyl transferase	9 3.3%	7 6.1%
Glucose serum fasting increased	13 4.8%	5 4.4%
Glucose serum fasting decreased	6 2.2%	0 0.0%
Potassium increased	13 4.8%	3 2.6%
Potassium decreased	14 5.2%	1 0.9%
Magnesium increased	1 0.4%	0 0.0%
Magnesium decreased	1 0.4%	0 0.0%
Phosphate decreased	17 6.3%	5 4.4%
Sodium increased	23 8.6%	4 3.5%
Sodium decreased	4 1.5%	0 0.0%

10. Secondary Outcome

Title	Number of Participants With Clinically Notable Vital Signs
Description	Abnormalities criteria included: low/high pulse rate (beats per minute [bpm]):<=50bpm with decrease from baseline >=15bpm/>=120bpm with increase from baseline >=15bpm; Low/high systolic blood pressure (millimeters of mercury [mmHg]): <=90mmHg with decrease from baseline >=20mmHg/>=160mmHg with increase from baseline >=20mmHg; Low/high diastolic blood pressure [mmHg]: <=50mmHg with decrease from baseline >=15mmHg/>=100mmHg with increase from baseline >=15mmHg; Low/high body weight (kilogram [kg]): >=20% decrease from baseline / >=10% increase from baseline; Low/high body temperature (degree Celsius [°C]): <=36°C / >= 37.5°C
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation. Here, "number analyzed" signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	114
Measure Type: Count of Participants; Unit of Measure: Participants
Sitting Pulse Rate - High	Number Analyzed	260 participants	106 participants
		4 1.5%	1 0.9%
Sitting Pulse Rate - Low	Number Analyzed	259 participants	105 participants
		3 1.2%	1 1.0%
Sitting systolic blood pressure - High	Number Analyzed	249 participants	102 participants
		43 17.3%	8 7.8%
Sitting systolic blood pressure -Low	Number Analyzed	260 participants	105 participants
		2 0.8%	4 3.8%
Sitting diastolic blood pressure - High	Number Analyzed	258 participants	104 participants
		28 10.9%	4 3.8%
Sitting diastolic blood pressure - Low	Number Analyzed	260 participants	105 participants
		2 0.8%	1 1.0%
Weight - High	Number Analyzed	261 participants	105 participants
		16 6.1%	1 1.0%
Weight - Low	Number Analyzed	261 participants	105 participants
		0 0.0%	0 0.0%
Body temperature - High	Number Analyzed	258 participants	105 participants
		15 5.8%	6 5.7%
Body temperature - Low	Number Analyzed	198 participants	79 participants
		90 45.5%	24 30.4%

11. Secondary Outcome

Title	Number of Participants With Notable Electrocardiogram (ECG) Values
Description	Criteria for notable ECG values were as follow: QT interval (in millisecond [msec]) new (newly occurring post-baseline value) greater than (>) 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Fredericia formula (QTcF) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; corrected QT interval by Bazett's formula (QTcB) in msec new (newly occurring post-baseline value) > 450, 480, 500, increase from baseline >30, increase from baseline >60; heart rate in bpm new (newly occurring post-baseline value) <60 and >100.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation. Here, "number analyzed" signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	114
Measure Type: Count of Participants; Unit of Measure: Participants
QT - New > 450 msec	Number Analyzed	249 participants	102 participants
		32 12.9%	8 7.8%
QT - New > 480 msec	Number Analyzed	259 participants	103 participants
		7 2.7%	1 1.0%
QT - New > 500 msec	Number Analyzed	260 participants	103 participants
		5 1.9%	0 0.0%
QT - Increase from baseline > 30 msec	Number Analyzed	261 participants	103 participants
		109 41.8%	33 32.0%
QT - Increase from baseline > 60 msec	Number Analyzed	261 participants	103 participants
		28 10.7%	5 4.9%
QTcF - New > 450 msec	Number Analyzed	243 participants	101 participants
		29 11.9%	15 14.9%
QTcF - New > 480 msec	Number Analyzed	261 participants	105 participants
		10 3.8%	1 1.0%
QTcF - New > 500 msec	Number Analyzed	262 participants	106 participants
		5 1.9%	1 0.9%
QTcF - Increase from baseline > 30 msec	Number Analyzed	262 participants	106 participants
		52 19.8%	25 23.6%
QTcF - Increase from baseline > 60 msec	Number Analyzed	262 participants	106 participants
		9 3.4%	5 4.7%
QTcB - New > 450 msec	Number Analyzed	217 participants	82 participants
		65 30.0%	26 31.7%
QTcB - New > 480 msec	Number Analyzed	250 participants	100 participants
		24 9.6%	8 8.0%
QTcB - New > 500 msec	Number Analyzed	253 participants	101 participants
		6 2.4%	6 5.9%
QTcB - Increase from baseline > 30 msec	Number Analyzed	255 participants	102 participants
		76 29.8%	36 35.3%
QTcB - Increase from baseline > 60 msec	Number Analyzed	255 participants	102 participants
		11 4.3%	9 8.8%
Heart rate - New < 60 bpm	Number Analyzed	219 participants	85 participants
		85 38.8%	13 15.3%
Heart rate - New > 100 bpm	Number Analyzed	255 participants	93 participants
		18 7.1%	16 17.2%

12. Secondary Outcome

Title	Number of Participants With Adverse Events of Special Interest: Cardiac Events
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Here, in this outcome measure data is reported for events falling in any of the grades.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	114
Measure Type: Count of Participants; Unit of Measure: Participants
	35 13.0%	2 1.8%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Findings in Physical Examination
Description	A complete physical examination included the examination of general appearance, skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems. If indicated based on medical history and/or symptoms, rectal, external genitalia, breast, and pelvic examinations were performed. Clinical significance in physical examination was reported as adverse events.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

No data was collected and analyzed for this outcome measure, any clinically significant physical examination findings were counted as adverse events and reported in safety section.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

14. Secondary Outcome

Title	Number of Participants With Adverse Events of Special Interest: Ocular Events
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Grade 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age appropriate instrumental ADL; Grade 3: Severe or medically significant but not immediately sight threatening; Hospitalization or prolongation of existing hospitalization indicated; disabling; limiting self-care ADL; Grade 4: Sight-threatening consequences; urgent intervention indicated; blindness (20/200 or worse) in the affected eye. Here, in this outcome measure data is reported for events falling in any of the grades.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	114
Measure Type: Count of Participants; Unit of Measure: Participants
	6 2.2%	0 0.0%

15. Secondary Outcome

Title	Plasma Concentration of Binimetinib
Description	[Not Specified]
Time Frame	Day 1 of Week 1: Pre-dose, 1, 1.5, 2, 10 hours post-dose; Day 1 of Weeks 4, 7: Pre-dose, 1.5 hours post-dose; Day 1 of Weeks 10, 13: Pre-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic analysis set (PAS) consisted of all participants who received at least one dose of binimetinib and had at least one evaluable post-baseline binimetinib concentration measurement. Here, "Overall Number of Participants Analyzed" = number of participants evaluable for this outcome measure. This outcome was planned to be evaluated only for binimetinib arm. Here, "number analyzed" signifies participants evaluable for this outcome measure for specified timeframes.

Arm/Group Title		Binimetinib (MEK162)
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		264
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Nanogram per milliliter
Week 1 Day 1, Pre-dose	Number Analyzed	253 participants
		64.4; (1132.3%)
Week 1 Day 1, 1 hour (hr) Post-dose	Number Analyzed	223 participants
		182; (237.6%)
Week 1 Day 1, 1.5 hr Post-dose	Number Analyzed	217 participants
		313; (71.6%)
Week 1 Day 1, 2 hr Post-dose	Number Analyzed	26 participants
		321; (64.4%)
Week 1 Day 1, 10 hr Post-dose	Number Analyzed	245 participants
		153; (52.6%)
Week 4 Day 1, Pre-dose	Number Analyzed	161 participants
		101; (100.8%)
Week 4 Day 1, 1.5 hr Post-dose	Number Analyzed	155 participants
		418; (51.9%)
Week 7 Day 1, Pre-dose	Number Analyzed	133 participants
		101; (97.7%)
Week 7 Day 1, 1.5 hr Post-dose	Number Analyzed	134 participants
		372; (63.4%)
Week 10 Day 1, Pre-dose	Number Analyzed	80 participants
		92.9; (60.6%)
Week 13 Day 1, Pre-dose	Number Analyzed	53 participants
		93.9; (89.8%)

16. Secondary Outcome

Title	Time to Definitive 10% Deterioration in Global Health Status Score of European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30)
Description	The time to definitive 10% deterioration was defined as the time from the date of randomization to the date of event, which was defined as death due to any cause or at least 10% worsening of the corresponding scale score, relative to baseline, with no later improvement above this threshold observed during the course of the study or death due to any cause. If a participant had no event prior to analysis cut-off or start of another anticancer therapy, time to deterioration was censored at the date of the last adequate health related quality of life (HRQoL) evaluation. EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life.
Time Frame	From baseline up to 77 weeks in binimetinib arm; From baseline up to 61 weeks for dacarbazine arm

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	269	133
Median (95% Confidence Interval); Unit of Measure: Months
	2.79; (1.64 to 4.24)	4.27 [1]; (2.86 to NA)

[1]

95% CI upper limit was not estimable due to very less number of participants with event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.96 to 2.13
	Estimation Comments	[Not Specified]

17. Secondary Outcome

Title	Change From Baseline in Global Health Status Score of EORTC QLQ-C30 at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-Treatment Follow-up Visit 1, 2, 3, 4, 5 and 6
Description	EORTC QLQ-C30: 5 functional scales (physical, role, cognitive, emotional, and social), a h global health status scale, 3 symptom scales (nausea/vomiting, pain, fatigue) and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). All scales and single-item measures range =0 to 100. High score for global health status = high quality of life. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Time Frame	Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants. Here, "Number analyzed" signifies number of participants evaluable at specified time points.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	133
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline	Number Analyzed	257 participants	113 participants
		68.35 (23.463)	70.50 (21.823)
Week 4 Day 1	Number Analyzed	223 participants	83 participants
		-5.75 (22.285)	-1.81 (17.512)
Week 7 Day 1	Number Analyzed	200 participants	67 participants
		-8.63 (22.562)	0.00 (15.691)
Week 13 Day 1	Number Analyzed	146 participants	31 participants
		-8.28 (19.659)	-1.34 (16.955)
Week 19 Day 1	Number Analyzed	87 participants	23 participants
		-8.05 (21.053)	-3.26 (22.296)
Week 25 Day 1	Number Analyzed	52 participants	12 participants
		-10.58 (21.775)	-3.47 (13.036)
Week 34 Day 1	Number Analyzed	24 participants	7 participants
		-6.25 (18.755)	3.57 (20.893)
Week 43 Day 1	Number Analyzed	11 participants	6 participants
		-11.36 (20.841)	-6.94 (23.224)
Week 52 Day 1	Number Analyzed	11 participants	2 participants
		-1.52 (20.006)	-8.33 (11.785)
Week 61 Day 1	Number Analyzed	5 participants	0 participants
		-10.00 (18.066)
Week 70 Day 1	Number Analyzed	2 participants	0 participants
		-20.83 (5.893)
End of Treatment	Number Analyzed	209 participants	89 participants
		-12.20 (22.512)	-6.74 (21.536)
30-day safety follow-up	Number Analyzed	71 participants	13 participants
		-8.10 (21.361)	-9.62 (14.372)
Post treatment follow-up 1	Number Analyzed	21 participants	32 participants
		-5.95 (19.211)	-8.59 (21.218)
Post treatment follow-up 2	Number Analyzed	1 participants	0 participants
		0.00 [1] (NA)
Post treatment follow-up 3	Number Analyzed	1 participants	0 participants
		16.67 [1] (NA)
Post treatment follow-up 4	Number Analyzed	2 participants	0 participants
		25.00 (11.785)
Post treatment follow-up 5	Number Analyzed	2 participants	0 participants
		25.00 (11.785)
Post treatment follow-up 6	Number Analyzed	1 participants	0 participants
		33.33 [1] (NA)

[1]

SD was not estimable due to very less number of participants with event.

18. Secondary Outcome

Title	Change From Baseline in EuroQoL-5 Dimensions- 5 Levels (EQ-5D-5L) Index Score at Weeks 4, 7, 13, 19, 25, 34, 43, 52, 61, 70, End of Treatment, Safety Follow-up Visit, Post-treatment Follow-up Visit 1, 2, 3, 4, 5 and 6
Description	EQ-5D-5L, is a standardized measure of health utility that provides a single index value for one's health status. EQ-5D-5L contained 1 item for each of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Index score: participant responses to the 5 dimensions reflected a specific health state that corresponded to a population preference weight for that state on a continuous scale of 0 (death) to 1 (perfect health). Higher index scores = better health state. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Time Frame	Both arms: Baseline, Day 1 Treatment Week (TW) 4,7,13,19,25,34,43,52; Post-treatment follow-up Visit (FUV) 1 to 6; Binimetinib: Day 1 TW61,70; End of treatment (EOT= TW73); Safety FUV=30 days post TW73; Dacarbazine: EOT=TW 57;Safety FUV=30 days post TW57

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants. Here, "Number analyzed" signifies number of participants evaluable at specified time points.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	133
Mean (Standard Deviation); Unit of Measure: Units on a scale
Baseline	Number Analyzed	257 participants	112 participants
		0.7780 (0.22464)	0.7657 (0.23003)
Week 4 Day 1	Number Analyzed	221 participants	83 participants
		-0.0422 (0.18291)	0.0110 (0.12135)
Week 7 Day 1	Number Analyzed	201 participants	67 participants
		-0.0397 (0.19154)	0.0132 (0.14084)
Week 13 Day 1	Number Analyzed	145 participants	32 participants
		-0.0773 (0.17543)	0.0198 (0.15236)
Week 19 Day 1	Number Analyzed	90 participants	23 participants
		-0.0576 (0.22503)	0.0257 (0.18052)
Week 25 Day 1	Number Analyzed	55 participants	12 participants
		-0.1563 (0.32142)	0.0657 (0.16052)
Week 34 Day 1	Number Analyzed	25 participants	6 participants
		-0.0801 (0.11141)	0.0617 (0.15254)
Week 43 Day 1	Number Analyzed	12 participants	6 participants
		-0.0170 (0.22978)	0.1060 (0.15033)
Week 52 Day 1	Number Analyzed	11 participants	2 participants
		-0.0389 (0.24609)	0.0000 (0.00000)
Week 61 Day 1	Number Analyzed	5 participants	0 participants
		0.0690 (0.21080)
Week 70 Day 1	Number Analyzed	2 participants	0 participants
		0.0120 (0.14001)
End of Treatment	Number Analyzed	210 participants	90 participants
		-0.0978 (0.23931)	-0.0540 (0.19164)
30-day safety follow-up	Number Analyzed	71 participants	13 participants
		-0.1165 (0.24410)	-0.0740 (0.17682)
Post treatment follow-up 1	Number Analyzed	22 participants	32 participants
		-0.0820 (0.11993)	-0.0438 (0.25374)
Post treatment follow-up 2	Number Analyzed	1 participants	0 participants
		-0.2480 [1] (NA)
Post treatment follow-up 3	Number Analyzed	1 participants	0 participants
		-0.1210 [1] (NA)
Post treatment follow-up 4	Number Analyzed	2 participants	0 participants
		0.1115 (0.15768)
Post treatment follow-up 5	Number Analyzed	2 participants	0 participants
		0.1730 (0.24466)
Post treatment follow-up 6	Number Analyzed	1 participants	0 participants
		0.2230 [1] (NA)

[1]

SD was not estimable due to very less number of participants with event.

19. Secondary Outcome

Title	Time to Definitive 1 Point Deterioration in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Description	ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 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, 3= capable of only limited self-care, confined to bed or chair more than 50% of waking hours, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair and 5= dead. Definitive deterioration is defined as on treatment death due to any cause or decrease in ECOG PS by at least one category from baseline score.
Time Frame	From baseline up to 73 weeks 3 days for binimetinib arm; From baseline up to 57 weeks 3 days for dacarbazine arm

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation. Here, "Overall Number of Participants Analyzed" = number of participants evaluable for this outcome measure.

Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed	262	105
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (5.62 to NA)	NA [2]; (NA to NA)

[1]

Median and upper limit of 95% CI, was not estimable due to very less number of participants with event.

[2]

Data was not estimable due to very less number of participants with event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Binimetinib (MEK162), Dacarbazine
	Comments	Log-rank test and Cox PH model were stratified by American joint committee on cancer stage, prior line immunotherapy and ECOG performance status. P-value was one tailed and was based on the log-rank score test. Hazard ratio and 95% CI was based on a Wald test from Cox model.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.995
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.20
	Confidence Interval	(2-Sided) 95%; 1.19 to 4.06
	Estimation Comments	[Not Specified]

20. Secondary Outcome

Title	Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Description	ECOG PS was used to assess the physical health of participants, and ranged from 0 (most active) to 5 (dead). ECOG PS grades: 0= fully active, able to carry on all pre-disease performance without restriction, 1= restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work, 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, 3= capable of only limited self-care, 4=completely disabled. cannot carry on any selfcare. Totally confined to bed or chair confined to bed or chair more than 50% of waking hours and 5= dead. Post-treatment tumor assessments follow up visits occurred at every 9 weeks if participants started new anticancer therapy.
Time Frame	For both arms: Baseline, Weeks 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, 37, 40, 43, 46, 49, 52, 55 and 30-day Follow-up For binimetinib only: Weeks 58, 61, 64, 67, 70, 73

Outcome Measure Data

Analysis Population Description

The safety set consisted all participants who received at least one dose of the study drug and had at least one valid post-baseline safety evaluation. Here, "Number Analyzed" signifies number of participants evaluable for specified rows.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	114
Measure Type: Count of Participants; Unit of Measure: Participants
Baseline : Grade 0	Number Analyzed	269 participants	114 participants
		193 71.7%	82 71.9%
Baseline: Grade 1	Number Analyzed	269 participants	114 participants
		76 28.3%	31 27.2%
Baseline : Grade 2	Number Analyzed	269 participants	114 participants
		0 0.0%	1 0.9%
Week 4 Day 1: Grade 0	Number Analyzed	256 participants	97 participants
		146 57.0%	66 68.0%
Week 4 Day 1: Grade 1	Number Analyzed	256 participants	97 participants
		101 39.5%	27 27.8%
Week 4 Day 1: Grade 2	Number Analyzed	256 participants	97 participants
		6 2.3%	4 4.1%
Week 4 Day 1: Grade 3	Number Analyzed	256 participants	97 participants
		3 1.2%	0 0.0%
Week 7 Day 1: Grade 0	Number Analyzed	236 participants	80 participants
		138 58.5%	51 63.7%
Week 7 Day 1: Grade 1	Number Analyzed	236 participants	80 participants
		84 35.6%	26 32.5%
Week 7 Day 1: Grade 2	Number Analyzed	236 participants	80 participants
		10 4.2%	3 3.8%
Week 7 Day 1: Grade 3	Number Analyzed	236 participants	80 participants
		3 1.3%	0 0.0%
Week 7 Day 1: Grade 4	Number Analyzed	236 participants	80 participants
		1 0.4%	0 0.0%
Week 10 Day 1: Grade 0	Number Analyzed	201 participants	51 participants
		118 58.7%	34 66.7%
Week 10 Day 1: Grade 1	Number Analyzed	201 participants	51 participants
		72 35.8%	15 29.4%
Week 10 Day 1: Grade 2	Number Analyzed	201 participants	51 participants
		8 4.0%	2 3.9%
Week 10 Day 1: Grade 3	Number Analyzed	201 participants	51 participants
		3 1.5%	0 0.0%
Week 13 Day 1: Grade 0	Number Analyzed	167 participants	43 participants
		93 55.7%	29 67.4%
Week 13 Day 1: Grade 1	Number Analyzed	167 participants	43 participants
		62 37.1%	14 32.6%
Week 13 Day 1: Grade 2	Number Analyzed	167 participants	43 participants
		11 6.6%	0 0.0%
Week 13 Day 1: Grade 3	Number Analyzed	167 participants	43 participants
		1 0.6%	0 0.0%
Week 16 Day 1: Grade 0	Number Analyzed	124 participants	30 participants
		70 56.5%	24 80.0%
Week 16 Day 1: Grade 1	Number Analyzed	124 participants	30 participants
		48 38.7%	5 16.7%
Week 16 Day 1: Grade 2	Number Analyzed	124 participants	30 participants
		5 4.0%	1 3.3%
Week 16 Day 1: Grade 4	Number Analyzed	124 participants	30 participants
		1 0.8%	0 0.0%
Week 19 Day 1: Grade 0	Number Analyzed	100 participants	28 participants
		53 53.0%	19 67.9%
Week 19 Day 1: Grade 1	Number Analyzed	100 participants	28 participants
		43 43.0%	7 25.0%
Week 19 Day 1:Grade 2	Number Analyzed	100 participants	28 participants
		4 4.0%	2 7.1%
Week 22 Day 1: Grade 0	Number Analyzed	72 participants	22 participants
		42 58.3%	17 77.3%
Week 22 Day 1: Grade 1	Number Analyzed	72 participants	22 participants
		26 36.1%	5 22.7%
Week 22 Day 1: Grade 2	Number Analyzed	72 participants	22 participants
		3 4.2%	0 0.0%
Week 22 Day 1: Grade 3	Number Analyzed	72 participants	22 participants
		1 1.4%	0 0.0%
Week 25 Day 1: Grade 0	Number Analyzed	58 participants	19 participants
		37 63.8%	13 68.4%
Week 25 Day 1: Grade 1	Number Analyzed	58 participants	19 participants
		19 32.8%	6 31.6%
Week 25 Day 1: Grade 2	Number Analyzed	58 participants	19 participants
		1 1.7%	0 0.0%
Week 25 Day 1: Grade 3	Number Analyzed	58 participants	19 participants
		1 1.7%	0 0.0%
Week 28 Day 1: Grade 0	Number Analyzed	46 participants	11 participants
		28 60.9%	9 81.8%
Week 28 Day 1: Grade 1	Number Analyzed	46 participants	11 participants
		15 32.6%	2 18.2%
Week 28 Day 1: Grade 2	Number Analyzed	46 participants	11 participants
		2 4.3%	0 0.0%
Week 28 Day 1: Grade 5	Number Analyzed	46 participants	11 participants
		1 2.2%	0 0.0%
Week 31 Day 1: Grade 0	Number Analyzed	34 participants	9 participants
		22 64.7%	7 77.8%
Week 31 Day 1: Grade 1	Number Analyzed	34 participants	9 participants
		11 32.4%	2 22.2%
Week 31 Day 1: Grade 2	Number Analyzed	34 participants	9 participants
		1 2.9%	0 0.0%
Week 34 Day 1: Grade 0	Number Analyzed	29 participants	10 participants
		20 69.0%	9 90.0%
Week 34 Day 1: Grade 1	Number Analyzed	29 participants	10 participants
		7 24.1%	1 10.0%
Week 34 Day 1: Grade 2	Number Analyzed	29 participants	10 participants
		2 6.9%	0 0.0%
Week 37 Day 1: Grade 0	Number Analyzed	20 participants	8 participants
		16 80.0%	7 87.5%
Week 37 Day 1: Grade 1	Number Analyzed	20 participants	8 participants
		4 20.0%	1 12.5%
Week 40 Day 1: Grade 0	Number Analyzed	15 participants	7 participants
		15 100.0%	6 85.7%
Week 40 Day 1: Grade 1	Number Analyzed	15 participants	7 participants
		0 0.0%	1 14.3%
Week 43 Day 1: Grade 0	Number Analyzed	14 participants	5 participants
		12 85.7%	5 100.0%
Week 43 Day 1: Grade 1	Number Analyzed	14 participants	5 participants
		1 7.1%	0 0.0%
Week 43 Day 1: Grade 2	Number Analyzed	14 participants	5 participants
		1 7.1%	0 0.0%
Week 46 Day 1: Grade 0	Number Analyzed	14 participants	4 participants
		11 78.6%	4 100.0%
Week 46 Day 1: Grade 1	Number Analyzed	14 participants	4 participants
		2 14.3%	0 0.0%
Week 46 Day 1: Grade 2	Number Analyzed	14 participants	4 participants
		1 7.1%	0 0.0%
Week 49 Day 1: Grade 0	Number Analyzed	11 participants	1 participants
		9 81.8%	1 100.0%
Week 49 Day 1: Grade 1	Number Analyzed	11 participants	1 participants
		2 18.2%	0 0.0%
Week 52 Day 1: Grade 0	Number Analyzed	11 participants	3 participants
		10 90.9%	2 66.7%
Week 52 Day 1: Grade 1	Number Analyzed	11 participants	3 participants
		1 9.1%	1 33.3%
Week 55 Day 1: Grade 0	Number Analyzed	10 participants	2 participants
		9 90.0%	1 50.0%
Week 55 Day 1: Grade 1	Number Analyzed	10 participants	2 participants
		1 10.0%	1 50.0%
Week 58 Day 1: Grade 0	Number Analyzed	8 participants	0 participants
		7 87.5%
Week 58 Day 1: Grade 1	Number Analyzed	8 participants	0 participants
		1 12.5%
Week 61 Day 1: Grade 0	Number Analyzed	5 participants	0 participants
		5 100.0%
Week 64 Day 1: Grade 0	Number Analyzed	4 participants	0 participants
		4 100.0%
Week 67 Day 1: Grade 0	Number Analyzed	3 participants	0 participants
		3 100.0%
Week 70 Day 1: Grade 0	Number Analyzed	2 participants	0 participants
		2 100.0%
Week 73 Day 1: Grade 0	Number Analyzed	1 participants	0 participants
		1 100.0%
Safety Follow up Visit: Grade 0	Number Analyzed	105 participants	44 participants
		42 40.0%	24 54.5%
Safety Follow up Visit: Grade 1	Number Analyzed	105 participants	44 participants
		41 39.0%	16 36.4%
Safety Follow up Visit: Grade 2	Number Analyzed	105 participants	44 participants
		14 13.3%	4 9.1%
Safety Follow up Visit: Grade 3	Number Analyzed	105 participants	44 participants
		4 3.8%	0 0.0%
Safety Follow up Visit: Grade 4	Number Analyzed	105 participants	44 participants
		4 3.8%	0 0.0%

21. Secondary Outcome

Title	Number of Participants With Neuroblastoma RAS Viral (V-ras) Oncogene Homolog (NRAS) Mutation Status at Baseline
Description	Number of participants with NRAS mutation status at baseline were reported.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

FAS consisted of all randomized participants. Here, "number analyzed" signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title		Binimetinib (MEK162)	Dacarbazine
Arm/Group Description:		Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
Overall Number of Participants Analyzed		269	133
Measure Type: Count of Participants; Unit of Measure: Participants
Wild Type	Number Analyzed	269 participants	133 participants
		0 0.0%	1 0.8%
Mutant: Q61K	Number Analyzed	269 participants	132 participants
		100 37.2%	51 38.6%
Mutant: Q61L	Number Analyzed	269 participants	132 participants
		32 11.9%	17 12.9%
Mutant: Q61R	Number Analyzed	269 participants	132 participants
		137 50.9%	64 48.5%

Adverse Events

Time Frame	From baseline up to 219.4 weeks for binimetinib arm; From baseline up to 123.9 weeks for dacarbazine arm
Adverse Event Reporting Description	Same event may appear as AE and serious AE, what is presented are distinct events. 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 study. Safety analysis set population included all participants who have received at least one dose of the study drug and had at least one valid post-baseline safety assessment.
Arm/Group Title	Binimetinib (MEK162)	Dacarbazine
Arm/Group Description	Participants received oral binimetinib 45 milligram (mg) (3*15 mg tablets) twice daily, until disease progression (PD), unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of binimetinib treatment exposure in the study was 215.4 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per Blinded Independent Review Committee (BIRC), withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.	Participants received intravenous (IV) dacarbazine 1000 mg per square meter (mg/m^2) once every 3 weeks until PD, unacceptable toxicity, death, physician decision, study termination or discontinuation due to any other reason (e.g., withdrawal of consent, lost to follow-up, start of a new anti-cancer therapy). Maximum duration of dacarbazine treatment exposure in the study was 119.9 weeks and participants were followed up to 30 days after last dose of study treatment. Participants who discontinued study treatment due to start of a new anti-cancer therapy, were followed up at every 9 weeks until documented progression per BIRC, withdrawal of consent, lost to follow-up, study closure or death whichever occurred first.
All-Cause Mortality
	Binimetinib (MEK162)	Dacarbazine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Binimetinib (MEK162)	Dacarbazine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	95/269 (35.32%)	26/114 (22.81%)
Blood and lymphatic system disorders
ANAEMIA * 1	2/269 (0.74%)	0/114 (0.00%)
FEBRILE NEUTROPENIA * 1	0/269 (0.00%)	1/114 (0.88%)
NEUTROPENIA * 1	0/269 (0.00%)	1/114 (0.88%)
PANCYTOPENIA * 1	0/269 (0.00%)	2/114 (1.75%)
THROMBOCYTOPENIA * 1	1/269 (0.37%)	0/114 (0.00%)
IRON DEFICIENCY ANAEMIA * 1	0/269 (0.00%)	1/114 (0.88%)
Cardiac disorders
ATRIAL FIBRILLATION * 1	1/269 (0.37%)	0/114 (0.00%)
TACHYARRHYTHMIA * 1	1/269 (0.37%)	1/114 (0.88%)
ANGINA PECTORIS * 1	1/269 (0.37%)	0/114 (0.00%)
ATRIAL FLUTTER * 1	1/269 (0.37%)	0/114 (0.00%)
ATRIOVENTRICULAR BLOCK * 1	1/269 (0.37%)	0/114 (0.00%)
ATRIOVENTRICULAR BLOCK FIRST DEGREE * 1	1/269 (0.37%)	0/114 (0.00%)
MITRAL VALVE DISEASE * 1	1/269 (0.37%)	0/114 (0.00%)
Eye disorders
RETINAL VEIN OCCLUSION * 1	4/269 (1.49%)	0/114 (0.00%)
RETINAL DETACHMENT * 1	1/269 (0.37%)	0/114 (0.00%)
RETINAL VEIN THROMBOSIS * 1	2/269 (0.74%)	0/114 (0.00%)
Gastrointestinal disorders
DIARRHOEA * 1	2/269 (0.74%)	0/114 (0.00%)
VOMITING * 1	3/269 (1.12%)	0/114 (0.00%)
MOUTH ULCERATION * 1	1/269 (0.37%)	0/114 (0.00%)
CONSTIPATION * 1	2/269 (0.74%)	0/114 (0.00%)
NAUSEA * 1	2/269 (0.74%)	0/114 (0.00%)
ABDOMINAL PAIN * 1	1/269 (0.37%)	1/114 (0.88%)
ABDOMINAL PAIN LOWER * 1	1/269 (0.37%)	0/114 (0.00%)
ABDOMINAL PAIN UPPER * 1	1/269 (0.37%)	0/114 (0.00%)
ASCITES * 1	1/269 (0.37%)	0/114 (0.00%)
AUTOIMMUNE PANCREATITIS * 1	1/269 (0.37%)	0/114 (0.00%)
COLITIS ISCHAEMIC * 1	1/269 (0.37%)	0/114 (0.00%)
DUODENAL PERFORATION * 1	1/269 (0.37%)	0/114 (0.00%)
HAEMORRHOIDS * 1	1/269 (0.37%)	0/114 (0.00%)
INTESTINAL PERFORATION * 1	1/269 (0.37%)	0/114 (0.00%)
INTUSSUSCEPTION * 1	1/269 (0.37%)	0/114 (0.00%)
LARGE INTESTINAL OBSTRUCTION * 1	1/269 (0.37%)	0/114 (0.00%)
MESENTERIC VEIN THROMBOSIS * 1	1/269 (0.37%)	0/114 (0.00%)
SUBILEUS * 1	1/269 (0.37%)	0/114 (0.00%)
General disorders
MALAISE * 1	0/269 (0.00%)	1/114 (0.88%)
PYREXIA * 1	1/269 (0.37%)	3/114 (2.63%)
GENERAL PHYSICAL HEALTH DETERIORATION * 1	10/269 (3.72%)	0/114 (0.00%)
AXILLARY PAIN * 1	1/269 (0.37%)	0/114 (0.00%)
FATIGUE * 1	1/269 (0.37%)	0/114 (0.00%)
MULTIPLE ORGAN DYSFUNCTION SYNDROME * 1	1/269 (0.37%)	0/114 (0.00%)
OEDEMA PERIPHERAL * 1	1/269 (0.37%)	0/114 (0.00%)
Hepatobiliary disorders
HEPATIC FAILURE * 1	1/269 (0.37%)	0/114 (0.00%)
CHOLECYSTITIS * 1	1/269 (0.37%)	0/114 (0.00%)
CHOLESTASIS * 1	0/269 (0.00%)	1/114 (0.88%)
Infections and infestations
SEPTIC SHOCK * 1	1/269 (0.37%)	0/114 (0.00%)
SKIN INFECTION * 1	3/269 (1.12%)	0/114 (0.00%)
LOWER RESPIRATORY TRACT INFECTION * 1	0/269 (0.00%)	1/114 (0.88%)
CELLULITIS * 1	2/269 (0.74%)	0/114 (0.00%)
ERYSIPELAS * 1	2/269 (0.74%)	0/114 (0.00%)
PYELONEPHRITIS ACUTE * 1	2/269 (0.74%)	0/114 (0.00%)
SEPSIS * 1	2/269 (0.74%)	2/114 (1.75%)
SOFT TISSUE INFECTION * 1	2/269 (0.74%)	0/114 (0.00%)
UROSEPSIS * 1	2/269 (0.74%)	0/114 (0.00%)
ABSCESS LIMB * 1	1/269 (0.37%)	0/114 (0.00%)
DERMO-HYPODERMITIS * 1	1/269 (0.37%)	0/114 (0.00%)
HERPES ZOSTER * 1	1/269 (0.37%)	0/114 (0.00%)
OSTEOMYELITIS * 1	1/269 (0.37%)	0/114 (0.00%)
PNEUMOCOCCAL SEPSIS * 1	1/269 (0.37%)	0/114 (0.00%)
PNEUMONIA * 1	1/269 (0.37%)	1/114 (0.88%)
VIRAL INFECTION * 1	1/269 (0.37%)	0/114 (0.00%)
LUNG INFECTION * 1	0/269 (0.00%)	1/114 (0.88%)
PERINEAL ABSCESS * 1	0/269 (0.00%)	1/114 (0.88%)
Injury, poisoning and procedural complications
MUSCLE INJURY * 1	1/269 (0.37%)	0/114 (0.00%)
FEMORAL NECK FRACTURE * 1	1/269 (0.37%)	0/114 (0.00%)
SUBDURAL HAEMATOMA * 1	1/269 (0.37%)	0/114 (0.00%)
TIBIA FRACTURE * 1	1/269 (0.37%)	0/114 (0.00%)
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED * 1	3/269 (1.12%)	0/114 (0.00%)
ALANINE AMINOTRANSFERASE INCREASED * 1	1/269 (0.37%)	0/114 (0.00%)
ASPARTATE AMINOTRANSFERASE INCREASED * 1	1/269 (0.37%)	0/114 (0.00%)
EJECTION FRACTION DECREASED * 1	1/269 (0.37%)	0/114 (0.00%)
ELECTROCARDIOGRAM QT PROLONGED * 1	1/269 (0.37%)	0/114 (0.00%)
HAEMOGLOBIN DECREASED * 1	1/269 (0.37%)	0/114 (0.00%)
INTRAOCULAR PRESSURE INCREASED * 1	1/269 (0.37%)	0/114 (0.00%)
BLOOD PRESSURE INCREASED * 1	1/269 (0.37%)	0/114 (0.00%)
EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS WORSENED * 1	1/269 (0.37%)	0/114 (0.00%)
GENERAL PHYSICAL CONDITION ABNORMAL * 1	1/269 (0.37%)	0/114 (0.00%)
Metabolism and nutrition disorders
DIABETIC METABOLIC DECOMPENSATION * 1	1/269 (0.37%)	0/114 (0.00%)
DECREASED APPETITE * 1	2/269 (0.74%)	0/114 (0.00%)
Musculoskeletal and connective tissue disorders
MUSCULAR WEAKNESS * 1	2/269 (0.74%)	0/114 (0.00%)
RHABDOMYOLYSIS * 1	1/269 (0.37%)	0/114 (0.00%)
INTERVERTEBRAL DISC PROTRUSION * 1	2/269 (0.74%)	0/114 (0.00%)
INTERVERTEBRAL DISC COMPRESSION * 1	1/269 (0.37%)	0/114 (0.00%)
OSTEONECROSIS * 1	1/269 (0.37%)	0/114 (0.00%)
PATHOLOGICAL FRACTURE * 1	1/269 (0.37%)	0/114 (0.00%)
BACK PAIN * 1	0/269 (0.00%)	2/114 (1.75%)
FLANK PAIN * 1	0/269 (0.00%)	1/114 (0.88%)
PAIN IN EXTREMITY * 1	0/269 (0.00%)	1/114 (0.88%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
TUMOUR HAEMORRHAGE * 1	0/269 (0.00%)	1/114 (0.88%)
CANCER PAIN * 1	1/269 (0.37%)	0/114 (0.00%)
MALIGNANT ASCITES * 1	1/269 (0.37%)	0/114 (0.00%)
Nervous system disorders
MYASTHENIC SYNDROME * 1	1/269 (0.37%)	0/114 (0.00%)
PERIPHERAL SENSORIMOTOR NEUROPATHY * 1	1/269 (0.37%)	0/114 (0.00%)
LETHARGY * 1	0/269 (0.00%)	1/114 (0.88%)
SPINAL CORD COMPRESSION * 1	2/269 (0.74%)	0/114 (0.00%)
CEREBRAL HAEMORRHAGE * 1	1/269 (0.37%)	0/114 (0.00%)
DROPPED HEAD SYNDROME * 1	1/269 (0.37%)	0/114 (0.00%)
HAEMORRHAGE INTRACRANIAL * 1	1/269 (0.37%)	0/114 (0.00%)
MOTOR DYSFUNCTION * 1	1/269 (0.37%)	0/114 (0.00%)
SCIATICA * 1	1/269 (0.37%)	0/114 (0.00%)
SUBARACHNOID HAEMORRHAGE * 1	1/269 (0.37%)	1/114 (0.88%)
TRANSIENT ISCHAEMIC ATTACK * 1	1/269 (0.37%)	0/114 (0.00%)
BRAIN OEDEMA * 1	0/269 (0.00%)	1/114 (0.88%)
CEREBROVASCULAR ACCIDENT * 1	0/269 (0.00%)	1/114 (0.88%)
DEMENTIA * 1	0/269 (0.00%)	1/114 (0.88%)
ENCEPHALOPATHY * 1	0/269 (0.00%)	1/114 (0.88%)
PROGRESSIVE SUPRANUCLEAR PALSY * 1	0/269 (0.00%)	1/114 (0.88%)
Psychiatric disorders
CONFUSIONAL STATE * 1	2/269 (0.74%)	0/114 (0.00%)
ABNORMAL BEHAVIOUR * 1	1/269 (0.37%)	0/114 (0.00%)
Renal and urinary disorders
ACUTE KIDNEY INJURY * 1	1/269 (0.37%)	0/114 (0.00%)
RENAL FAILURE * 1	2/269 (0.74%)	0/114 (0.00%)
NEPHROLITHIASIS * 1	1/269 (0.37%)	0/114 (0.00%)
Respiratory, thoracic and mediastinal disorders
PNEUMONITIS * 1	2/269 (0.74%)	0/114 (0.00%)
PULMONARY EMBOLISM * 1	4/269 (1.49%)	0/114 (0.00%)
DYSPNOEA * 1	3/269 (1.12%)	2/114 (1.75%)
LUNG DISORDER * 1	1/269 (0.37%)	0/114 (0.00%)
ASPIRATION * 1	1/269 (0.37%)	0/114 (0.00%)
HAEMOPTYSIS * 1	1/269 (0.37%)	0/114 (0.00%)
PLEURAL EFFUSION * 1	1/269 (0.37%)	0/114 (0.00%)
RESPIRATORY ARREST * 1	1/269 (0.37%)	0/114 (0.00%)
PNEUMOTHORAX * 1	0/269 (0.00%)	1/114 (0.88%)
Skin and subcutaneous tissue disorders
HYPERHIDROSIS * 1	0/269 (0.00%)	1/114 (0.88%)
DERMATITIS ACNEIFORM * 1	1/269 (0.37%)	0/114 (0.00%)
PSORIASIS * 1	1/269 (0.37%)	0/114 (0.00%)
RASH MACULO-PAPULAR * 1	1/269 (0.37%)	0/114 (0.00%)
Vascular disorders
HYPERTENSIVE CRISIS * 1	2/269 (0.74%)	0/114 (0.00%)
HAEMORRHAGE * 1	2/269 (0.74%)	0/114 (0.00%)
AORTIC DILATATION * 1	1/269 (0.37%)	0/114 (0.00%)
DEEP VEIN THROMBOSIS * 1	1/269 (0.37%)	0/114 (0.00%)
EMBOLISM * 1	1/269 (0.37%)	0/114 (0.00%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA v 19.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Binimetinib (MEK162)	Dacarbazine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	266/269 (98.88%)	100/114 (87.72%)
Blood and lymphatic system disorders
ANAEMIA * 1	19/269 (7.06%)	11/114 (9.65%)
LYMPHOPENIA * 1	7/269 (2.60%)	7/114 (6.14%)
NEUTROPENIA * 1	4/269 (1.49%)	21/114 (18.42%)
THROMBOCYTOPENIA * 1	2/269 (0.74%)	17/114 (14.91%)
LEUKOPENIA * 1	0/269 (0.00%)	8/114 (7.02%)
Eye disorders
RETINAL DETACHMENT * 1	35/269 (13.01%)	0/114 (0.00%)
EYELID OEDEMA * 1	28/269 (10.41%)	0/114 (0.00%)
VISION BLURRED * 1	20/269 (7.43%)	1/114 (0.88%)
SUBRETINAL FLUID * 1	19/269 (7.06%)	0/114 (0.00%)
MACULAR OEDEMA * 1	17/269 (6.32%)	0/114 (0.00%)
PERIORBITAL OEDEMA * 1	14/269 (5.20%)	0/114 (0.00%)
Gastrointestinal disorders
DIARRHOEA * 1	109/269 (40.52%)	15/114 (13.16%)
NAUSEA * 1	85/269 (31.60%)	35/114 (30.70%)
VOMITING * 1	58/269 (21.56%)	15/114 (13.16%)
CONSTIPATION * 1	39/269 (14.50%)	22/114 (19.30%)
ABDOMINAL PAIN * 1	24/269 (8.92%)	8/114 (7.02%)
DRY MOUTH * 1	22/269 (8.18%)	1/114 (0.88%)
ABDOMINAL PAIN UPPER * 1	16/269 (5.95%)	3/114 (2.63%)
General disorders
OEDEMA PERIPHERAL * 1	97/269 (36.06%)	5/114 (4.39%)
FATIGUE * 1	68/269 (25.28%)	38/114 (33.33%)
ASTHENIA * 1	44/269 (16.36%)	19/114 (16.67%)
PYREXIA * 1	34/269 (12.64%)	16/114 (14.04%)
PERIPHERAL SWELLING * 1	15/269 (5.58%)	2/114 (1.75%)
FACE OEDEMA * 1	14/269 (5.20%)	0/114 (0.00%)
Infections and infestations
RASH PUSTULAR * 1	18/269 (6.69%)	0/114 (0.00%)
NASOPHARYNGITIS * 1	17/269 (6.32%)	5/114 (4.39%)
ERYSIPELAS * 1	15/269 (5.58%)	0/114 (0.00%)
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED * 1	119/269 (44.24%)	3/114 (2.63%)
ASPARTATE AMINOTRANSFERASE INCREASED * 1	39/269 (14.50%)	5/114 (4.39%)
EJECTION FRACTION DECREASED * 1	35/269 (13.01%)	2/114 (1.75%)
ALANINE AMINOTRANSFERASE INCREASED * 1	23/269 (8.55%)	8/114 (7.02%)
INTRAOCULAR PRESSURE INCREASED * 1	19/269 (7.06%)	0/114 (0.00%)
WEIGHT DECREASED * 1	13/269 (4.83%)	6/114 (5.26%)
GAMMA-GLUTAMYLTRANSFERASE INCREASED * 1	8/269 (2.97%)	7/114 (6.14%)
PLATELET COUNT DECREASED * 1	2/269 (0.74%)	11/114 (9.65%)
NEUTROPHIL COUNT DECREASED * 1	1/269 (0.37%)	8/114 (7.02%)
Metabolism and nutrition disorders
DECREASED APPETITE * 1	34/269 (12.64%)	19/114 (16.67%)
Musculoskeletal and connective tissue disorders
MYALGIA * 1	28/269 (10.41%)	3/114 (2.63%)
BACK PAIN * 1	19/269 (7.06%)	6/114 (5.26%)
ARTHRALGIA * 1	18/269 (6.69%)	3/114 (2.63%)
NECK PAIN * 1	17/269 (6.32%)	2/114 (1.75%)
MUSCULAR WEAKNESS * 1	16/269 (5.95%)	0/114 (0.00%)
PAIN IN EXTREMITY * 1	11/269 (4.09%)	6/114 (5.26%)
Nervous system disorders
DYSGEUSIA * 1	21/269 (7.81%)	2/114 (1.75%)
HEADACHE * 1	18/269 (6.69%)	9/114 (7.89%)
DIZZINESS * 1	17/269 (6.32%)	3/114 (2.63%)
Psychiatric disorders
INSOMNIA * 1	17/269 (6.32%)	8/114 (7.02%)
Respiratory, thoracic and mediastinal disorders
DYSPNOEA * 1	27/269 (10.04%)	5/114 (4.39%)
COUGH * 1	20/269 (7.43%)	10/114 (8.77%)
Skin and subcutaneous tissue disorders
DERMATITIS ACNEIFORM * 1	106/269 (39.41%)	1/114 (0.88%)
RASH * 1	96/269 (35.69%)	2/114 (1.75%)
DRY SKIN * 1	37/269 (13.75%)	2/114 (1.75%)
PRURITUS * 1	27/269 (10.04%)	2/114 (1.75%)
SKIN FISSURES * 1	26/269 (9.67%)	0/114 (0.00%)
ALOPECIA * 1	24/269 (8.92%)	3/114 (2.63%)
RASH MACULO-PAPULAR * 1	23/269 (8.55%)	0/114 (0.00%)
ERYTHEMA * 1	17/269 (6.32%)	2/114 (1.75%)
Vascular disorders
HYPERTENSION * 1	36/269 (13.38%)	4/114 (3.51%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA v 19.0

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):

Dummer R, Schadendorf D, Ascierto PA, Arance A, Dutriaux C, Di Giacomo AM, Rutkowski P, Del Vecchio M, Gutzmer R, Mandala M, Thomas L, Demidov L, Garbe C, Hogg D, Liszkay G, Queirolo P, Wasserman E, Ford J, Weill M, Sirulnik LA, Jehl V, Bozon V, Long GV, Flaherty K. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017 Apr;18(4):435-445. doi: 10.1016/S1470-2045(17)30180-8. Epub 2017 Mar 9.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01763164
• Other Study ID Numbers: CMEK162A2301; C4211002 ( Other Identifier: Alias Study Number ); 2012-003593-51 ( EudraCT Number )
• First Submitted: January 4, 2013
• First Posted: January 8, 2013
• Results First Submitted: February 11, 2021
• Results First Posted: March 22, 2021
• Last Update Posted: March 22, 2021