Trial Outcomes & Findings for LGX818 for Patients With BRAFV600 Mutated Tumors (NCT NCT01981187)

NCT ID: NCT01981187

Last Updated: 2021-03-26

Results Overview

CBR for solid tumors was defined as percentage of participants with complete response (CR) or partial response (PR), or stable disease (SD) for greater than or equal to (\>=) 16 weeks. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Up to 13.3 months

Results posted on

2021-03-26

Participant Flow

Participant milestones

Participant milestones
Measure	LGX818 (Encorafenib) Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Overall Study STARTED	12
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	LGX818 (Encorafenib) Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Overall Study Participant/guardian decision	2
Overall Study Physician Decision	1
Overall Study Disease progression	2
Overall Study Adverse Event	7

Baseline Characteristics

LGX818 for Patients With BRAFV600 Mutated Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Age, Continuous	57.6 Years STANDARD_DEVIATION 11.17 • n=99 Participants
Sex: Female, Male Female	7 Participants n=99 Participants
Sex: Female, Male Male	5 Participants n=99 Participants

PRIMARY outcome

Timeframe: Up to 13.3 months

Population: The full analysis set included all participants who received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Clinical Benefit Rate (CBR) for Solid Tumors as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	25 percentage of participants Interval 5.5 to 57.2

SECONDARY outcome

Timeframe: From the first dose study treatment until the first documented CR or PR (maximum up to 13.3 months)

Population: The full analysis set included all participants who received at least one dose of study drug.

ORR for solid tumors was defined as the percentage of participants achieving an overall best response of CR or PR as assessed per RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Overall Response Rate (ORR) for Solid Tumors as Per RECIST Version 1.1	0 percentage of participants Interval 0.0 to 26.5

SECONDARY outcome

Timeframe: From the date of first dose until the first documentation of PD, relapse, censored date or death, whichever occurred first (maximum up to 13.3 months)

Population: The full analysis set included all participants who received at least one dose of study drug.

PFS for solid tumors was defined as the time from the date of first dose of study drug to the date of first documented disease progression (PD) or relapse or death due to any cause within 30 days of the last dose. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. Participants who had no event were censored at the date of last adequate tumor assessment.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Progression-Free Survival (PFS) for Solid Tumors as Per RECIST Version 1.1	NA months Interval 1.8 to Median and upper limit of 95% CI were not estimable due to low number of participants with an event.

SECONDARY outcome

Timeframe: From date of the first dose until the date of death, censored date (maximum up to 13.3 months)

Population: The full analysis set included all participants who received at least one dose of study drug.

OS for solid tumors was defined as the time from the date of first dose of study drug to the date of death due to any cause. For participants who were alive at the time of analysis, the data was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Overall Survival (OS) for Solid Tumors	13.3 months Interval 8.4 to 13.3

SECONDARY outcome

Timeframe: From first documentation of response to first documentation of PD or relapse or death (maximum up to 13.3 months)

Population: Data for this outcome measure was not analyzed due to low overall response rate among participants.

DOR for solid tumors was defined as the time from the first documented response (CR or PR) to the date of first documented PD or relapse or death due to any cause, whichever occurred first. As per RECIST v1.1, CR was defined as disappearance of all target and non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months)

Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.

Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, severity was graded as Grade 1: asymptomatic/mild symptoms, clinical/diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local/noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe/medically significant but not immediately life-threatening, hospitalization/prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated. TEAE was defined as event with onset dates occurring during the on-treatment period. CTCAE Grade 5 (death) was not used in this study.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 3	10 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 1	0 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 2	2 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Graded According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 4	0 Participants

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Population: The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment. Here 'number analyzed' signifies number of participants evaluable for each specified row.

Change from baseline in systolic and diastolic blood pressure in millimeter of mercury (mmHg) in sitting position was reported.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Baseline	129.4 mmHg Standard Deviation 17.33
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 2, Day 1	2.4 mmHg Standard Deviation 4.34
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 3, Day 1	4.0 mmHg Standard Deviation 23.56
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 4, Day 1	-0.3 mmHg Standard Deviation 14.52
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 5, Day 1	7.8 mmHg Standard Deviation 11.32
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 6, Day 1	-5.3 mmHg Standard Deviation 18.01
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 7, Day 1	0.0 mmHg Standard Deviation 12.49
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 8, Day 1	1.5 mmHg Standard Deviation 4.95
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 9, Day 1	2.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 10, Day 1	9.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 11, Day 1	10.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at Cycle 12, Day 1	15.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Systolic Blood Pressure: Change at End of Treatment	8.7 mmHg Standard Deviation 18.95
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Baseline	78.1 mmHg Standard Deviation 9.33
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 2, Day 1	-0.1 mmHg Standard Deviation 8.46
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 3, Day 1	1.4 mmHg Standard Deviation 11.26
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 4, Day 1	-1.3 mmHg Standard Deviation 5.62
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 5, Day 1	-0.5 mmHg Standard Deviation 4.12
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 6, Day 1	-0.7 mmHg Standard Deviation 8.33
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 7, Day 1	1.7 mmHg Standard Deviation 9.71
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 8, Day 1	1.0 mmHg Standard Deviation 4.24
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 9, Day 1	0.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 10, Day 1	9.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 11, Day 1	5.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at Cycle 12, Day 1	0.0 mmHg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Systolic and Diastolic Blood Pressure Diastolic Blood Pressure: Change at End of Treatment	4.7 mmHg Standard Deviation 12.12

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in pulse rate in beats per minute (bpm) in sitting position was reported.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Sitting Pulse Rate Baseline	84.8 bpm Standard Deviation 18.17
Change From Baseline in Sitting Pulse Rate Change at Cycle 2, Day 1	4.9 bpm Standard Deviation 8.18
Change From Baseline in Sitting Pulse Rate Change at Cycle 3, Day 1	-1.2 bpm Standard Deviation 18.67
Change From Baseline in Sitting Pulse Rate Change at Cycle 4, Day 1	-19.0 bpm Standard Deviation 23.86
Change From Baseline in Sitting Pulse Rate Change at Cycle 5, Day 1	-5.0 bpm Standard Deviation 4.24
Change From Baseline in Sitting Pulse Rate Change at Cycle 6, Day 1	-10.3 bpm Standard Deviation 8.33
Change From Baseline in Sitting Pulse Rate Change at Cycle 7, Day 1	-4.3 bpm Standard Deviation 16.86
Change From Baseline in Sitting Pulse Rate Change at Cycle 8, Day 1	-1.0 bpm Standard Deviation 42.43
Change From Baseline in Sitting Pulse Rate Change at Cycle 9, Day 1	-24.0 bpm Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Sitting Pulse Rate Change at Cycle 10, Day 1	-25.0 bpm Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Sitting Pulse Rate Change at Cycle 11, Day 1	-19.0 bpm Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Sitting Pulse Rate Change at Cycle 12, Day 1	-23.0 bpm Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Sitting Pulse Rate Change at End of Treatment	-2.7 bpm Standard Deviation 9.33

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in body temperature in degree Celsius was reported.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Body Temperature Baseline	36.7 degree Celsius Standard Deviation 0.30
Change From Baseline in Body Temperature Change at Cycle 2, Day 1	-0.1 degree Celsius Standard Deviation 0.32
Change From Baseline in Body Temperature Change at Cycle 3, Day 1	0.0 degree Celsius Standard Deviation 0.25
Change From Baseline in Body Temperature Change at Cycle 4, Day 1	-0.3 degree Celsius Standard Deviation 0.13
Change From Baseline in Body Temperature Change at Cycle 5, Day 1	0.0 degree Celsius Standard Deviation 0.13
Change From Baseline in Body Temperature Change at Cycle 6, Day 1	-0.4 degree Celsius Standard Deviation 0.36
Change From Baseline in Body Temperature Change at Cycle 7, Day 1	-0.4 degree Celsius Standard Deviation 0.42
Change From Baseline in Body Temperature Change at Cycle 8, Day 1	-0.4 degree Celsius Standard Deviation 0.42
Change From Baseline in Body Temperature Change at Cycle 9, Day 1	-0.5 degree Celsius Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Temperature Change at Cycle 10, Day 1	-0.5 degree Celsius Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Temperature Change at Cycle 11, Day 1	-0.8 degree Celsius Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Temperature Change at Cycle 12, Day 1	-0.4 degree Celsius Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Temperature Change at End of Treatment	-0.1 degree Celsius Standard Deviation 0.38

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in respiratory rate in breaths per minute was reported.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Respiratory Rate Baseline	17.6 breaths per minute Standard Deviation 1.31
Change From Baseline in Respiratory Rate Change at Cycle 2, Day 1	0.0 breaths per minute Standard Deviation 1.41
Change From Baseline in Respiratory Rate Change at Cycle 3, Day 1	2.0 breaths per minute Standard Deviation 4.47
Change From Baseline in Respiratory Rate Change at Cycle 4, Day 1	-1.0 breaths per minute Standard Deviation 1.15
Change From Baseline in Respiratory Rate Change at Cycle 5, Day 1	-0.5 breaths per minute Standard Deviation 1.00
Change From Baseline in Respiratory Rate Change at Cycle 6, Day 1	0.0 breaths per minute Standard Deviation 2.00
Change From Baseline in Respiratory Rate Change at Cycle 7, Day 1	0.7 breaths per minute Standard Deviation 1.15
Change From Baseline in Respiratory Rate Change at Cycle 8, Day 1	-1.0 breaths per minute Standard Deviation 1.41
Change From Baseline in Respiratory Rate Change at Cycle 9, Day 1	0.0 breaths per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Respiratory Rate Change at Cycle 10, Day 1	0.0 breaths per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Respiratory Rate Change at Cycle 11, Day 1	0.0 breaths per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Respiratory Rate Change at Cycle 12, Day 1	1.0 breaths per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Respiratory Rate Change at End of Treatment	-0.1 breaths per minute Standard Deviation 1.76

SECONDARY outcome

Timeframe: Baseline, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in body weight in kilogram (Kg) was reported

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Body Weight Change at Cycle 3, Day 1	-3.4 Kg Standard Deviation 2.77
Change From Baseline in Body Weight Change at Cycle 4, Day 1	-6.5 Kg Standard Deviation 3.85
Change From Baseline in Body Weight Baseline	87.0 Kg Standard Deviation 21.77
Change From Baseline in Body Weight Change at Cycle 2, Day 1	-3.4 Kg Standard Deviation 2.48
Change From Baseline in Body Weight Change at Cycle 5, Day 1	-5.8 Kg Standard Deviation 3.96
Change From Baseline in Body Weight Change at Cycle 6, Day 1	-6.0 Kg Standard Deviation 4.57
Change From Baseline in Body Weight Change at Cycle 7, Day 1	-6.8 Kg Standard Deviation 5.96
Change From Baseline in Body Weight Change at Cycle 8, Day 1	-6.4 Kg Standard Deviation 4.81
Change From Baseline in Body Weight Change at Cycle 9, Day 1	-12.5 Kg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Weight Change at Cycle 10, Day 1	-10.3 Kg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Weight Change at Cycle 11, Day 1	-9.4 Kg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Weight Change at Cycle 12, Day 1	-9.0 Kg Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Body Weight Change at End of Treatment	-3.7 Kg Standard Deviation 3.43

SECONDARY outcome

Timeframe: Baseline up to maximum of 30 days after the last dose of study treatment (up to 13.3 months)

Number of participants with shifts from baseline in hematology and serum chemistry laboratory parameters, were graded and reported as low, normal and high as assessed by Common terminology criteria for adverse events (CTCAE) v4.03. 'Low' refers to participants with values that were below lower limit of normal with no observation above the upper limit of normal; 'High' refers to participants with values that were above the upper limit of normal with no observation below the lower limit of normal; 'Low and High' refers to participants with values that were below the lower limit of normal and values that were above the upper limit of normal.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T4, Normal	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Red Blood Cell Count, Normal	6 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Red Blood Cell Count, Low	5 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Red Blood Cell Count, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Hematocrit, Low	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Hematocrit, Normal	4 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Hematocrit, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Eosinophils, Low	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Eosinophils, Normal	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Eosinophils, High	3 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Basophils, Low	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Basophils, Normal	9 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Basophils, High	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Monocytes, Low	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Monocytes, Normal	3 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Monocytes, High	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Neutrophils, Low	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Neutrophils, Normal	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Neutrophils, High	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lymphocytes, Low	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lymphocytes, Normal	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lymphocytes, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Blood Urea Nitrogen, Low	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Blood Urea Nitrogen, Normal	8 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Blood Urea Nitrogen, High	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Bicarbonate, Low	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Bicarbonate, Normal	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Bicarbonate, High	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lactate Dehydrogenase, Low	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lactate Dehydrogenase, Normal	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Lactate Dehydrogenase, High	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Serum Total Protein, Low	3 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Serum Total Protein, Normal	8 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Serum Total Protein, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Low-Density Lipoprotein, Low	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Low-Density Lipoprotein, Normal	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Low-Density Lipoprotein, High	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities High-Density Lipoprotein, Low	6 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities High-Density Lipoprotein, Normal	4 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities High-Density Lipoprotein, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Thyroid-Stimulating Hormone, Low	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Thyroid-Stimulating Hormone, Normal	6 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities Thyroid-Stimulating Hormone, High	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T3, Low	2 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T3, Normal	7 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T3, High	0 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T4, Low	1 Participants
Number of Participants With Shifts From Baseline in Hematology and Serum Chemistry Laboratory Abnormalities T4, High	1 Participants

SECONDARY outcome

Timeframe: Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in QTcF, QT, QRS, and PR duration were reported. QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QRS interval is the time from electrocardiogram Q wave to the end of the S wave, corresponding to ventricle depolarization. PR interval is the time between the beginning of the P wave and the start of the QRS interval, corresponding to the end of atrial depolarization and onset of ventricular depolarization.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 2, Day 1	-7.4 milliseconds Standard Deviation 26.50
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Baseline	423.9 milliseconds Standard Deviation 24.84
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 1, Day 15	0.6 milliseconds Standard Deviation 16.11
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 2, Day 1	3.1 milliseconds Standard Deviation 28.33
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 2, Day 15	-62.0 milliseconds Standard Deviation 99.90
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 3, Day 1	7.0 milliseconds Standard Deviation 14.30
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 4, Day 1	1.3 milliseconds Standard Deviation 11.50
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 5, Day 1	0.7 milliseconds Standard Deviation 1.53
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 6, Day 1	-6.0 milliseconds Standard Deviation 9.17
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 7, Day 1	-18.5 milliseconds Standard Deviation 6.36
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 8, Day 1	-28.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 9, Day 1	-36.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at Cycle 10, Day 1	-26.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QTcF: Change at End of Treatment	4.5 milliseconds Standard Deviation 25.69
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Baseline	394.2 milliseconds Standard Deviation 36.19
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 1, Day 15	-4.3 milliseconds Standard Deviation 18.27
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 2, Day 1	-2.4 milliseconds Standard Deviation 29.47
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 2, Day 15	-47.0 milliseconds Standard Deviation 79.97
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 3, Day 1	6.6 milliseconds Standard Deviation 30.59
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 4, Day 1	-6.7 milliseconds Standard Deviation 25.40
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 5, Day 1	5.3 milliseconds Standard Deviation 11.02
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 6, Day 1	-6.7 milliseconds Standard Deviation 24.68
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 7, Day 1	-33.0 milliseconds Standard Deviation 29.70
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 8, Day 1	-78.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 9, Day 1	-29.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at Cycle 10, Day 1	-18.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QT: Change at End of Treatment	-0.3 milliseconds Standard Deviation 20.04
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Baseline	93.9 milliseconds Standard Deviation 12.75
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 1, Day 15	-2.3 milliseconds Standard Deviation 4.68
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 2, Day 1	-1.1 milliseconds Standard Deviation 13.50
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 2, Day 15	0.6 milliseconds Standard Deviation 6.31
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 3, Day 1	-2.4 milliseconds Standard Deviation 2.61
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 4, Day 1	-5.0 milliseconds Standard Deviation 3.61
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 5, Day 1	-3.3 milliseconds Standard Deviation 3.06
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 6, Day 1	0.0 milliseconds Standard Deviation 4.00
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 7, Day 1	-5.0 milliseconds Standard Deviation 1.41
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 8, Day 1	-8.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 9, Day 1	5.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at Cycle 10, Day 1	6.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration QRS: Change at End of Treatment	-6.1 milliseconds Standard Deviation 6.01
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Baseline	145.8 milliseconds Standard Deviation 25.13
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 1, Day 15	-7.3 milliseconds Standard Deviation 19.60
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 2, Day 15	1.2 milliseconds Standard Deviation 11.37
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 3, Day 1	-0.6 milliseconds Standard Deviation 19.59
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 4, Day 1	-6.0 milliseconds Standard Deviation 2.00
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 5, Day 1	7.3 milliseconds Standard Deviation 16.29
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 6, Day 1	2.7 milliseconds Standard Deviation 21.39
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 7, Day 1	10.0 milliseconds Standard Deviation 22.63
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 8, Day 1	-14.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 9, Day 1	-13.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at Cycle 10, Day 1	-8.0 milliseconds Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in QT Interval Corrected According to the Formula of Fridericia (QTcF), QT, QRS, and PR Duration PR: Change at End of Treatment	-6.9 milliseconds Standard Deviation 21.96

SECONDARY outcome

Timeframe: Baseline, Day 15 of Cycle 1, 2, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 (each cycle of 28 days), and End of treatment (up to 7 days after study treatment discontinuation)

Change from baseline in heart rate in terms of beats per minute was reported.

Outcome measures

Outcome measures
Measure	LGX818 (Encorafenib) n=12 Participants Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Change From Baseline in Heart Rate Change at Cycle 10, Day 1	-4.0 beats per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Heart Rate Change at End of Treatment	2.0 beats per minute Standard Deviation 10.68
Change From Baseline in Heart Rate Baseline	77.3 beats per minute Standard Deviation 15.79
Change From Baseline in Heart Rate Change at Cycle 1, Day 15	2.9 beats per minute Standard Deviation 9.01
Change From Baseline in Heart Rate Change at Cycle 2, Day 1	4.1 beats per minute Standard Deviation 12.31
Change From Baseline in Heart Rate Change at Cycle 2, Day 15	-1.0 beats per minute Standard Deviation 9.30
Change From Baseline in Heart Rate Change at Cycle 3, Day 1	-0.4 beats per minute Standard Deviation 12.66
Change From Baseline in Heart Rate Change at Cycle 4, Day 1	7.3 beats per minute Standard Deviation 14.74
Change From Baseline in Heart Rate Change at Cycle 5, Day 1	-3.0 beats per minute Standard Deviation 5.29
Change From Baseline in Heart Rate Change at Cycle 6, Day 1	-0.7 beats per minute Standard Deviation 7.77
Change From Baseline in Heart Rate Change at Cycle 7, Day 1	7.0 beats per minute Standard Deviation 11.31
Change From Baseline in Heart Rate Change at Cycle 8, Day 1	27.0 beats per minute Standard Deviation NA Standard deviation was not estimated due to single participant.
Change From Baseline in Heart Rate Change at Cycle 9, Day 1	-2.0 beats per minute Standard Deviation NA Standard deviation was not estimated due to single participant.

Adverse Events

LGX818 (Encorafenib)

Serious events: 4 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LGX818 (Encorafenib) n=12 participants at risk Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Acute kidney injury	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Fatigue	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.

Other adverse events

Other adverse events
Measure	LGX818 (Encorafenib) n=12 participants at risk Participants received an oral dose of 300 mg of LGX818 (Encorafenib) capsules (3 capsules of 100 mg) once daily in each cycle (1 cycle = 28 days) until disease progression, unacceptable toxicity, death or discontinuation from study treatment for any other reason. Maximum study treatment exposure was approximately of 12 months and participants were followed up to 13.3 months approximately.
Blood and lymphatic system disorders Anaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Blood and lymphatic system disorders Lymphadenopathy	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Cardiac disorders Palpitations	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Ear and labyrinth disorders Ear pain	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Conjunctival disorder	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Dry eye	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Eye irritation	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Eye pruritus	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Lacrimation increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Photophobia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Eye disorders Vision blurred	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Nausea	75.0% 9/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Vomiting	58.3% 7/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Constipation	33.3% 4/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Abdominal pain	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Diarrhoea	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Gastric fistula	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Gastrooesophageal reflux disease	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Haematochezia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Pancreatitis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Gastrointestinal disorders Retching	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Fatigue	58.3% 7/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Asthenia	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Influenza like illness	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Mucosal inflammation	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Oedema peripheral	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Axillary pain	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Chills	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Face oedema	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Nodule	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
General disorders Pyrexia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Infections and infestations Oral candidiasis	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Infections and infestations Urinary tract infection	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Infections and infestations Candida infection	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Infections and infestations Folliculitis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Infections and infestations Gastrointestinal infection	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Electrocardiogram QT prolonged	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Weight decreased	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Blood creatine phosphokinase increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Blood creatinine decreased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Blood creatinine increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Blood urea increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Gamma-glutamyltransferase increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations International normalised ratio increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Lipase increased	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Prothrombin time prolonged	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Investigations Urine leukocyte esterase	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Decreased appetite	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperglycaemia	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Dehydration	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperlipidaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperphosphataemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyperuricaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hypocalcaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hypokalaemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Metabolism and nutrition disorders Hyponatraemia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Back pain	41.7% 5/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 4/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in extremity	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Myalgia	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Arthritis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Bone pain	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Muscle spasms	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Neck pain	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Musculoskeletal and connective tissue disorders Pain in jaw	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm skin	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Dysplastic naevus	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Dizziness	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Headache	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Paraesthesia	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Dysaesthesia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Narcolepsy	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Neuropathy peripheral	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Nervous system disorders Somnolence	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Psychiatric disorders Depression	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Psychiatric disorders Anxiety	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Psychiatric disorders Insomnia	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Acute kidney injury	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Glycosuria	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Haematuria	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Micturition urgency	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Renal and urinary disorders Proteinuria	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Reproductive system and breast disorders Scrotal oedema	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Atelectasis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Respiratory, thoracic and mediastinal disorders Haemoptysis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Rash	50.0% 6/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Pruritus	41.7% 5/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	33.3% 4/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Erythema	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin exfoliation	25.0% 3/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Alopecia	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Dry skin	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Keratosis pilaris	16.7% 2/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Acne	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Dermatitis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Eczema	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Hyperkeratosis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Lentigo	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Pain of skin	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Papule	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Pigmentation disorder	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Pruritus generalised	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Rash follicular	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Rash maculo-papular	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin burning sensation	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin discolouration	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin fissures	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin hypopigmentation	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin lesion	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Skin and subcutaneous tissue disorders Skin tightness	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Vascular disorders Deep vein thrombosis	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Vascular disorders Hypertension	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.
Vascular disorders Orthostatic hypotension	8.3% 1/12 • From screening up to 30 days after the last dose of study treatment (maximum up to 13.3 months) Same event may appear as both AE and SAE. An event may be categorized as serious in 1 participant and non-serious in other, or participant may have experienced both SAE and non-SAE. The safety set included all participants who received at least one dose of study treatment and had at least one post-baseline safety assessment.

Additional Information

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Results disclosure agreements

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

Restriction type: OTHER