Study of Selective BRAF Kinase Inhibitor Dabrafenib Monotherapy Twice Daily and in Combination With Dabrafenib Twice Daily and Trametinib Once Daily in Combination Therapy in Subjects With BRAF V600E Mutation Positive Metastatic (Stage IV) Non-small Cell Lung Cancer.

• ClinicalTrials.gov Identifier: NCT01336634
• Recruitment Status: Completed
• First Posted: April 18, 2011
• Results First Posted: December 7, 2017
• Last Update Posted: April 4, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Cancer
• Interventions: Drug: Dabrafenib; Drug: Trametinib
• Enrollment: 177

Participant Flow

Recruitment Details	The study was conducted in 50 sites across 11 countries: Netherlands(2), United States(15), Germany(4), Spain(7), France(8), Italy(3), Taiwan(2), South Korea(3), United Kingdom(3), Japan(2), Norway(1)
Pre-assignment Details

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Period Title: Overall Study
Started [1]	84	57	36 [2]
2nd Line Plus All Treated [3]	78	57	0
1st Line All Treated [4]	6	2	34
Crossover [5]	20	0	0
Completed [6]	70	49	27
Not Completed	14	8	9
Reason Not Completed
Study closed/terminated	5	6	6
Lost to Follow-up	2	1	1
Physician Decision	1	1	0
Withdrawal by Subject	6	0	2
[1] All participants who received at least one dose of study treatment were included in the All Treated Population (ATP); [2] includes 34 subjects from Cohort C and 2 subjects enrolled as protocol deviations from Cohort B.; [3] All Treated Population who had relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease.; [4] All Treated Population who had not received any prior anti-cancer therapy for metastatic disease.; [5] All Treated Population who were assigned to monotherapy cohort and elected to crossover to combination treatment following disease progression on monotherapy.; [6] Study ended when progression of disease had occurred in all patients in Cohorts B and C, a minimum of 70% of subjects had died in each cohort, or five years had passed since the last subject's first dose, whichever came first.

Baseline Characteristics

Arm/Group Title		Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Total
Arm/Group Description		Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Total of all reporting groups
Overall Number of Baseline Participants		84	57	36	177
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	84 participants	57 participants	36 participants	177 participants
		64.8 (10.51)	65.1 (10.14)	67.8 (11.00)	65.5 (10.50)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	84 participants	57 participants	36 participants	177 participants
	Female	44 52.4%	28 49.1%	22 61.1%	94 53.1%
	Male	40 47.6%	29 50.9%	14 38.9%	83 46.9%
Race/Ethnicity, Customized; Measure Type: Number; Unit of measure: Participants	Number Analyzed	84 participants	57 participants	36 participants	177 participants
White		64	49	30	143
Asian		18	4	3	25
African American Heritage		2	0	0	2
Native Hawaiian or other Pacific islander		0	0	1	1
Black or African American		0	2	1	3
Other		0	2	1	3
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	84 participants	57 participants	36 participants	177 participants
	Grade 0	20 23.8%	17 29.8%	13 36.1%	50 28.2%
	Grade 1	52 61.9%	35 61.4%	22 61.1%	109 61.6%
	Grade 2	12 14.3%	5 8.8%	1 2.8%	18 10.2%
		[1] Measure Description: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) score classifies participants according to their functional impairment, with scores ranging from 0 (fully active) to 5 (dead). ECOG PS: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2 = ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours

Outcome Measures

1. Primary Outcome

Title	Overall Response Rate (ORR)
Description	ORR was defined as the percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) by investigator assessment as per RECIST v1 .1 criteria. Specifically, ORR = (number of subjects with a confirmed best overall response of CR or PR) divided by the total number of subjects in the corresponding analysis population.
Time Frame	From study treatment start date until first documented complete response or partial response, assessed up to approximately 50 months

Outcome Measure Data

Analysis Population Description

All Treated Population (ATP).

Arm/Group Title	Cohort A (Dabrafenib Monotherapy)	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants who have relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
Overall Number of Participants Analyzed	78	57	36	20
Measure Type: Count of Participants; Unit of Measure: Participants
	27 34.6%	39 68.4%	23 63.9%	4 20.0%

2. Secondary Outcome

Title	Progression Free Survival (PFS) Based on Local Investigator Assessment
Description	Progression Free Survival (PFS) was defined as the time from study treatment start date to the date of first radiologically documented progression or death due to any cause. If a patient did not progress or die at the time of the analysis data cut-off or start of new antineoplastic therapy, PFS was censored at the date of the last adequate tumor assessment before the earliest of the cut-off date or the start date of additional anti-neoplastic therapy. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria RECIST v1.1, as 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 and/or unequivocal progression of the non-target lesions and/or appearance of a new lesion. In addition to the relative increase of 20%, the sum must demonstrate an absolute increase of at least 5 mm.
Time Frame	From study treatment start date until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 113 months

Outcome Measure Data

Analysis Population Description

All Treated Population (ATP). Only participants with an evaluable PFS events were included in the analysis.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy)	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants who have relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
Overall Number of Participants Analyzed	65	48	28	18
Median (95% Confidence Interval); Unit of Measure: Months
	5.4; (2.8 to 6.9)	10.2; (6.9 to 16.7)	10.8; (7.0 to 14.5)	11.0; (3.0 to 18.7)

3. Secondary Outcome

Title	Duration of Response (DoR) Based on Local Investigator Assessment
Description	Duration of Response (DoR) was defined as the time from the first documented occurrence of response (PR or CR) until the date of the first documented progression based on RECIST v1.1 or death.
Time Frame	From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 113 months

Outcome Measure Data

Analysis Population Description

All Treated Population (ATP). Only responders (PR or CR) were included in the analysis.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy)	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants who have relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
Overall Number of Participants Analyzed	27	39	23	4
Median (95% Confidence Interval); Unit of Measure: Months
	11.8; (5.4 to 23.5)	9.8; (6.9 to 18.3)	10.2; (8.3 to 15.2)	13.4; (7.6 to 19.3)

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall Survival (OS) was defined as the time from first dose until death due to any cause. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact.
Time Frame	From study treatment start date until date of of death from any cause, assessed up to approximately 113 months

Outcome Measure Data

Analysis Population Description

All Treated Population (ATP). No separate OS analysis was conducted for cross over patient, as they were included in Cohort A (Dabrafenib Monotherapy Second-Line Plus).

Arm/Group Title	Cohort A (Dabrafenib Monotherapy)	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants who have relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Overall Number of Participants Analyzed	67	49	27
Median (95% Confidence Interval); Unit of Measure: Months
	12.7; (7.3 to 16.3)	18.2; (14.3 to 28.6)	17.3; (12.3 to 40.2)

5. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events
Description	The distribution of adverse events (AE) was done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Time Frame	From study treatment start date till 30 days safety follow-up, assessed up to approximately 81 months

Outcome Measure Data

Analysis Population Description

All Treated Population (ATP)

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
Overall Number of Participants Analyzed	84	57	36	20
Measure Type: Count of Participants; Unit of Measure: Participants
Treatment Emergent Adverse Events (TAEs)	82 97.6%	54 94.7%	36 100.0%	20 100.0%
Treatment Emergent Serious Adverse Events (TESAEs)	37 44.0%	38 66.7%	24 66.7%	9 45.0%
Deaths due to AE causally related to treatment	2 2.4%	0 0.0%	0 0.0%	0 0.0%

6. Secondary Outcome

Title	Apparent Clearance (CL/F) of Dabrafenib
Description	Blood samples from participants were collected for population pharmacokinetic analysis including the apparent base clearance (CL/F) following oral dosing of dabrafenib. Concentrations of dabrafenib was determined in plasma samples using the currently approved analytical methodology.
Time Frame	Week 3, Week 6, Week 12 and Week 18

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of dabrafenib in the Cohort A (Dabrafenib Monotherapy) and in the doublets combination (Dabrafenib + Trametinib) Cohort B and C and provided an evaluable PK profile.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Overall Number of Participants Analyzed	76	53	30
Geometric Mean (95% Confidence Interval); Unit of Measure: Liter/hour (L/hr)
	30.5; (29.1 to 32.0)	21.4; (19.37 to 23.70)	23.9; (22.02 to 25.87)

7. Secondary Outcome

Title	Oral Volume of Distribution (V/F) of Dabrafenib
Description	Blood samples from participants were collected for population pharmacokinetic analysis including the oral volume of distribution (V/F) following oral dosing of dabrafenib. Blood samples from participants were collected for population pharmacokinetic analysis including the apparent base clearance (CL/F) following oral dosing of dabrafenib. Concentrations of dabrafenib was determined in plasma samples using the currently approved analytical methodology.
Time Frame	Week 3, Week 6, Week 12 and Week 18

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of dabrafenib in the Cohort A (Dabrafenib Monotherapy) and in the doublets combination (Dabrafenib + Trametinib) Cohort B and C and provided an evaluable PK profile.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Overall Number of Participants Analyzed	76	53	30
Geometric Mean (95% Confidence Interval); Unit of Measure: Liter (L)
	50.6; (47.4 to 54.0)	38.1; (30.93 to 46.97)	48.1; (42.15 to 54.95)

8. Secondary Outcome

Title	Apparent Clearance (CL/F) of Trametinib
Description	Blood samples from participants were collected for population pharmacokinetic analysis including the apparent base clearance (CL/F) following oral dosing of trametinib. Blood samples from participants were collected for population pharmacokinetic analysis including the apparent base clearance (CL/F) following oral dosing of dabrafenib. Concentrations of trametinib was determined in plasma samples using the currently approved analytical methodology.
Time Frame	Week 3, Week 6, Week 12 and Week 18

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of trametinib in the doublets combination (Dabrafenib + Trametinib) Cohort B and C and provided an evaluable PK profile.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Overall Number of Participants Analyzed	0	54	30
Geometric Mean (95% Confidence Interval); Unit of Measure: Liter/hour (L/hr)
		4.9; (4.62 to 5.19)	5.03; (4.64 to 5.46)

9. Secondary Outcome

Title	Oral Volume of Distribution (V/F) of Trametinib
Description	Blood samples from participants were collected for population pharmacokinetic analysis including the oral volume of distribution (V/F) following oral dosing of trametinib. Concentrations of trametinib was determined in plasma samples using the currently approved analytical methodology.
Time Frame	Week 3, Week 6, Week 12 and Week 18

Outcome Measure Data

Analysis Population Description

All subjects who received at least one dose of trametinib in the doublets combination (Dabrafenib + Trametinib) Cohort B and C and provided an evaluable PK profile.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.
Overall Number of Participants Analyzed	0	54	30
Geometric Mean (95% Confidence Interval); Unit of Measure: Liter (L)
		91.98; (78.58 to 107.66)	103.48; (84.58 to 126.59)

10. Post-Hoc Outcome

Title	All Collected Deaths
Description	On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration with dabrafenib and trametinib of 81 months (study treatment with dabrafenib and trametinib ranged from 0.3 to 80.0 months). Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 9 years. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.
Time Frame	up to 81 months (study treatment with dabrafenib and trametinib), up to approximately 9 years (study duration)

Outcome Measure Data

Analysis Population Description

Clinical database population; all treated patients.

Arm/Group Title	Cohort A (Dabrafenib Monotherapy)	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description:	Participants who have relapsed or progressed after receiving at least one line of prior anti-cancer therapy for metastatic disease received dabrafenib 150 mg BID. It was continued until disease progression or death or unacceptable AEs or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
Overall Number of Participants Analyzed	84	57	36	20
Measure Type: Count of Participants; Unit of Measure: Participants
On-treatment deaths	15 17.9%	12 21.1%	5 13.9%	4 20.0%
Post-treatment deaths	38 45.2%	38 66.7%	21 58.3%	13 65.0%
All deaths	53 63.1%	50 87.7%	26 72.2%	17 85.0%

Adverse Events

Time Frame	Adverse events were reported from first dose of study treatment until end of study treatment plus 30 days, up to approximately 81 months (study treatment with dabrafenib and trametinib ranged from 0.3 to 80.0 months).
Adverse Event Reporting Description	Any sign or symptom that occurs during the treatment period plus 30 days post-treatment.
Arm/Group Title	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
Arm/Group Description	Participants with or without prior systemic anti-cancer therapy received Dabrafenib 150 mg BID until disease progression, death, or unacceptable adverse event(s) (AEs) or investigator discretion to discontinue or decision to crossover from monotherapy to combination therapy.	Participants who had received 1-3 prior lines of systemic anti-cancer therapies for advanced stage/metastatic disease received Dabrafenib 150 mg BID and Trametinib 2 mg once daily (OD). Treatment continued until disease progression, death, or unacceptable AEs or investigator discretion to discontinue.	Participants who had not received any prior systemic anti-cancer for metastatic disease therapies were given Dabrafenib 150 mg BID and Trametinib 2 mg OD. Treatment continued until disease progression, death, or unacceptable AEs or at investigator discretion to discontinue.	Crossover - Double Combination (Dabrafenib+Trametinib): Participants received Dabrafenib 150 mg BID in combination with Trametinib 2 mg once daily and continued treatment until disease progression, death, or unacceptable adverse event.
All-Cause Mortality
	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	15/84 (17.86%)	12/57 (21.05%)	5/36 (13.89%)	4/20 (20.00%)
Serious Adverse Events
	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	37/84 (44.05%)	38/57 (66.67%)	24/36 (66.67%)	9/20 (45.00%)
Blood and lymphatic system disorders
Anaemia † 1	0/84 (0.00%)	3/57 (5.26%)	1/36 (2.78%)	0/20 (0.00%)
Febrile neutropenia † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Lymphopenia † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Neutropenia † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pancytopenia † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Splenic thrombosis † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Cardiac disorders
Arrhythmia † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Atrial fibrillation † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Cardiac arrest † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Cardiopulmonary failure † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pericardial effusion † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Sinus bradycardia † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Tachycardia † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Ventricular fibrillation † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Vertigo positional † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Eye disorders
Detachment of retinal pigment epithelium † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Macular hole † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Macular oedema † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Retinal dystrophy † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Uveitis † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Gastrointestinal disorders
Abdominal pain † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	1/20 (5.00%)
Abdominal pain upper † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Ascites † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Colitis † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Colitis ischaemic † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Constipation † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	1/20 (5.00%)
Diarrhoea † 1	0/84 (0.00%)	1/57 (1.75%)	1/36 (2.78%)	1/20 (5.00%)
Diverticulum intestinal haemorrhagic † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Duodenal ulcer haemorrhage † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Enterovesical fistula † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Gastric haemorrhage † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Gastritis † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Gastrointestinal pain † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Gastrointestinal toxicity † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Haematemesis † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Ileus † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Intestinal mass † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Intestinal obstruction † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Large intestinal obstruction † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Melaena † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Nausea † 1	1/84 (1.19%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Oesophageal stenosis † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Pancreatic duct stenosis † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pancreatitis acute † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Retroperitoneal haemorrhage † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Toothache † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Vomiting † 1	1/84 (1.19%)	2/57 (3.51%)	2/36 (5.56%)	0/20 (0.00%)
General disorders
Asthenia † 1	1/84 (1.19%)	2/57 (3.51%)	1/36 (2.78%)	0/20 (0.00%)
Chest discomfort † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Chest pain † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Chills † 1	1/84 (1.19%)	1/57 (1.75%)	1/36 (2.78%)	0/20 (0.00%)
Fatigue † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
General physical health deterioration † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Inflammation † 1	1/84 (1.19%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Malaise † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pyrexia † 1	5/84 (5.95%)	10/57 (17.54%)	4/36 (11.11%)	1/20 (5.00%)
Systemic inflammatory response syndrome † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Hepatobiliary disorders
Cholecystitis acute † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Hepatocellular injury † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Malignant biliary obstruction † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Infections and infestations
Bacterial infection † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Bronchitis † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Cystitis † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Device related infection † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Furuncle † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Gastritis viral † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Gastroenteritis viral † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Influenza † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Legionella infection † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pneumonia † 1	2/84 (2.38%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Pyelonephritis † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Respiratory tract infection † 1	3/84 (3.57%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Respiratory tract infection bacterial † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Sepsis † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Septic shock † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Urinary tract infection † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Viral infection † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Injury, poisoning and procedural complications
Incisional hernia † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Multiple injuries † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Stoma site haemorrhage † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Toxicity to various agents † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Investigations
Alanine aminotransferase increased † 1	1/84 (1.19%)	1/57 (1.75%)	5/36 (13.89%)	0/20 (0.00%)
Aspartate aminotransferase increased † 1	0/84 (0.00%)	1/57 (1.75%)	3/36 (8.33%)	0/20 (0.00%)
Blood alkaline phosphatase increased † 1	0/84 (0.00%)	1/57 (1.75%)	1/36 (2.78%)	0/20 (0.00%)
Blood creatinine increased † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	1/20 (5.00%)
C-reactive protein increased † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Ejection fraction decreased † 1	2/84 (2.38%)	4/57 (7.02%)	3/36 (8.33%)	1/20 (5.00%)
Gamma-glutamyltransferase increased † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Lymphocyte count decreased † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
White blood cell count decreased † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Metabolism and nutrition disorders
Decreased appetite † 1	1/84 (1.19%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Dehydration † 1	0/84 (0.00%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Diabetes mellitus † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Hypercalcaemia † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Hyperglycaemia † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Hyperkalaemia † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Hyponatraemia † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Hypophosphataemia † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Malnutrition † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain † 1	0/84 (0.00%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Lumbar spinal stenosis † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Myalgia † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma † 1	4/84 (4.76%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Bowen's disease † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Colon adenoma † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Endometrial adenocarcinoma † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Hepatocellular carcinoma † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Keratoacanthoma † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Lip squamous cell carcinoma † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Lung neoplasm malignant † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Neoplasm progression † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Squamous cell carcinoma † 1	1/84 (1.19%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Squamous cell carcinoma of skin † 1	7/84 (8.33%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Nervous system disorders
Cerebral haemorrhage † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Cerebrovascular accident † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Dizziness † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Encephalopathy † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Facial paresis † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Haemorrhage intracranial † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Headache † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Hemiparesis † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Neurological decompensation † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Neuropathy peripheral † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Peripheral sensory neuropathy † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Seizure † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Subarachnoid haemorrhage † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Transient ischaemic attack † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Psychiatric disorders
Anxiety † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Confusional state † 1	1/84 (1.19%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Disorientation † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Renal and urinary disorders
Haematuria † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Renal artery thrombosis † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Renal failure † 1	0/84 (0.00%)	3/57 (5.26%)	0/36 (0.00%)	1/20 (5.00%)
Tubulointerstitial nephritis † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Urinary bladder haemorrhage † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Urinary retention † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Cough † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Dyspnoea † 1	1/84 (1.19%)	2/57 (3.51%)	1/36 (2.78%)	1/20 (5.00%)
Haemoptysis † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Pleural effusion † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pneumonia aspiration † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Pneumonitis † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Pneumothorax † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pneumothorax spontaneous † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Pulmonary embolism † 1	0/84 (0.00%)	1/57 (1.75%)	2/36 (5.56%)	1/20 (5.00%)
Respiratory arrest † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Respiratory distress † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	0/20 (0.00%)
Respiratory failure † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Blister † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Rash † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	1/20 (5.00%)
Rash maculo-papular † 1	0/84 (0.00%)	0/57 (0.00%)	1/36 (2.78%)	0/20 (0.00%)
Transient acantholytic dermatosis † 1	1/84 (1.19%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Vascular disorders
Circulatory collapse † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Hypotension † 1	0/84 (0.00%)	2/57 (3.51%)	2/36 (5.56%)	0/20 (0.00%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cohort A (Dabrafenib Monotherapy): Dabrafenib Monotherapy 150mg BID	Cohort B - Double Combination (Dabrafenib+Trametinib) mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Cohort C - Double Combination (Dabrafenib+Trametinib) Naive mBRAF V600E: DAB 150MG BID, TRA 2mG QD	Crossover - Double Combination (Dabrafenib+Trametinib): DAB 150MG BID, TRA 2mG QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	82/84 (97.62%)	54/57 (94.74%)	36/36 (100.00%)	20/20 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	11/84 (13.10%)	8/57 (14.04%)	7/36 (19.44%)	1/20 (5.00%)
Leukopenia † 1	4/84 (4.76%)	5/57 (8.77%)	2/36 (5.56%)	0/20 (0.00%)
Lymphopenia † 1	6/84 (7.14%)	2/57 (3.51%)	2/36 (5.56%)	2/20 (10.00%)
Neutropenia † 1	2/84 (2.38%)	11/57 (19.30%)	1/36 (2.78%)	3/20 (15.00%)
Thrombocytopenia † 1	5/84 (5.95%)	5/57 (8.77%)	0/36 (0.00%)	2/20 (10.00%)
Cardiac disorders
Atrial fibrillation † 1	1/84 (1.19%)	4/57 (7.02%)	1/36 (2.78%)	0/20 (0.00%)
Atrioventricular block † 1	1/84 (1.19%)	0/57 (0.00%)	1/36 (2.78%)	2/20 (10.00%)
Bradycardia † 1	0/84 (0.00%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Sinus bradycardia † 1	0/84 (0.00%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Tachycardia † 1	2/84 (2.38%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Ear and labyrinth disorders
Vertigo † 1	1/84 (1.19%)	5/57 (8.77%)	1/36 (2.78%)	3/20 (15.00%)
Eye disorders
Cataract † 1	2/84 (2.38%)	2/57 (3.51%)	1/36 (2.78%)	2/20 (10.00%)
Dry eye † 1	4/84 (4.76%)	6/57 (10.53%)	3/36 (8.33%)	0/20 (0.00%)
Eye pain † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Periorbital oedema † 1	0/84 (0.00%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Photopsia † 1	0/84 (0.00%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Vision blurred † 1	5/84 (5.95%)	2/57 (3.51%)	3/36 (8.33%)	0/20 (0.00%)
Visual acuity reduced † 1	3/84 (3.57%)	5/57 (8.77%)	0/36 (0.00%)	0/20 (0.00%)
Visual impairment † 1	3/84 (3.57%)	4/57 (7.02%)	2/36 (5.56%)	1/20 (5.00%)
Gastrointestinal disorders
Abdominal distension † 1	1/84 (1.19%)	1/57 (1.75%)	0/36 (0.00%)	2/20 (10.00%)
Abdominal pain † 1	9/84 (10.71%)	6/57 (10.53%)	6/36 (16.67%)	2/20 (10.00%)
Abdominal pain upper † 1	4/84 (4.76%)	8/57 (14.04%)	0/36 (0.00%)	1/20 (5.00%)
Anal incontinence † 1	1/84 (1.19%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Constipation † 1	10/84 (11.90%)	11/57 (19.30%)	6/36 (16.67%)	6/20 (30.00%)
Diarrhoea † 1	17/84 (20.24%)	18/57 (31.58%)	15/36 (41.67%)	5/20 (25.00%)
Dry mouth † 1	2/84 (2.38%)	4/57 (7.02%)	3/36 (8.33%)	2/20 (10.00%)
Dyspepsia † 1	3/84 (3.57%)	5/57 (8.77%)	3/36 (8.33%)	0/20 (0.00%)
Dysphagia † 1	3/84 (3.57%)	3/57 (5.26%)	2/36 (5.56%)	0/20 (0.00%)
Gastritis † 1	2/84 (2.38%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Gastrooesophageal reflux disease † 1	4/84 (4.76%)	3/57 (5.26%)	0/36 (0.00%)	2/20 (10.00%)
Nausea † 1	24/84 (28.57%)	24/57 (42.11%)	21/36 (58.33%)	9/20 (45.00%)
Toothache † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	2/20 (10.00%)
Vomiting † 1	18/84 (21.43%)	24/57 (42.11%)	11/36 (30.56%)	6/20 (30.00%)
General disorders
Asthenia † 1	25/84 (29.76%)	21/57 (36.84%)	4/36 (11.11%)	3/20 (15.00%)
Chest pain † 1	4/84 (4.76%)	5/57 (8.77%)	0/36 (0.00%)	1/20 (5.00%)
Chills † 1	12/84 (14.29%)	15/57 (26.32%)	10/36 (27.78%)	3/20 (15.00%)
Fatigue † 1	24/84 (28.57%)	11/57 (19.30%)	15/36 (41.67%)	2/20 (10.00%)
Feeling cold † 1	1/84 (1.19%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Gait disturbance † 1	1/84 (1.19%)	0/57 (0.00%)	2/36 (5.56%)	1/20 (5.00%)
Hyperthermia † 1	0/84 (0.00%)	3/57 (5.26%)	1/36 (2.78%)	0/20 (0.00%)
Influenza like illness † 1	2/84 (2.38%)	4/57 (7.02%)	5/36 (13.89%)	0/20 (0.00%)
Malaise † 1	5/84 (5.95%)	3/57 (5.26%)	4/36 (11.11%)	1/20 (5.00%)
Mucosal inflammation † 1	6/84 (7.14%)	6/57 (10.53%)	2/36 (5.56%)	1/20 (5.00%)
Non-cardiac chest pain † 1	5/84 (5.95%)	0/57 (0.00%)	1/36 (2.78%)	1/20 (5.00%)
Oedema peripheral † 1	3/84 (3.57%)	22/57 (38.60%)	13/36 (36.11%)	5/20 (25.00%)
Pain † 1	2/84 (2.38%)	0/57 (0.00%)	4/36 (11.11%)	1/20 (5.00%)
Pyrexia † 1	31/84 (36.90%)	25/57 (43.86%)	22/36 (61.11%)	9/20 (45.00%)
Infections and infestations
Bronchitis † 1	6/84 (7.14%)	6/57 (10.53%)	0/36 (0.00%)	3/20 (15.00%)
Conjunctivitis † 1	2/84 (2.38%)	3/57 (5.26%)	1/36 (2.78%)	1/20 (5.00%)
Folliculitis † 1	4/84 (4.76%)	4/57 (7.02%)	0/36 (0.00%)	1/20 (5.00%)
Gastroenteritis † 1	2/84 (2.38%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Influenza † 1	1/84 (1.19%)	2/57 (3.51%)	2/36 (5.56%)	0/20 (0.00%)
Laryngitis † 1	0/84 (0.00%)	2/57 (3.51%)	0/36 (0.00%)	2/20 (10.00%)
Nasopharyngitis † 1	8/84 (9.52%)	7/57 (12.28%)	7/36 (19.44%)	3/20 (15.00%)
Pneumonia † 1	2/84 (2.38%)	6/57 (10.53%)	5/36 (13.89%)	0/20 (0.00%)
Rhinitis † 1	5/84 (5.95%)	7/57 (12.28%)	3/36 (8.33%)	0/20 (0.00%)
Upper respiratory tract infection † 1	8/84 (9.52%)	1/57 (1.75%)	1/36 (2.78%)	0/20 (0.00%)
Urinary tract infection † 1	5/84 (5.95%)	5/57 (8.77%)	7/36 (19.44%)	2/20 (10.00%)
Injury, poisoning and procedural complications
Contusion † 1	2/84 (2.38%)	1/57 (1.75%)	3/36 (8.33%)	0/20 (0.00%)
Fall † 1	2/84 (2.38%)	2/57 (3.51%)	1/36 (2.78%)	2/20 (10.00%)
Limb injury † 1	0/84 (0.00%)	0/57 (0.00%)	3/36 (8.33%)	1/20 (5.00%)
Thermal burn † 1	0/84 (0.00%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Investigations
Alanine aminotransferase increased † 1	4/84 (4.76%)	5/57 (8.77%)	2/36 (5.56%)	0/20 (0.00%)
Amylase increased † 1	0/84 (0.00%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Aspartate aminotransferase increased † 1	3/84 (3.57%)	6/57 (10.53%)	3/36 (8.33%)	2/20 (10.00%)
Blood alkaline phosphatase increased † 1	5/84 (5.95%)	11/57 (19.30%)	1/36 (2.78%)	0/20 (0.00%)
Blood creatine phosphokinase increased † 1	0/84 (0.00%)	6/57 (10.53%)	1/36 (2.78%)	2/20 (10.00%)
Blood creatinine increased † 1	3/84 (3.57%)	6/57 (10.53%)	1/36 (2.78%)	0/20 (0.00%)
C-reactive protein increased † 1	1/84 (1.19%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Lipase increased † 1	2/84 (2.38%)	4/57 (7.02%)	0/36 (0.00%)	1/20 (5.00%)
Weight decreased † 1	15/84 (17.86%)	9/57 (15.79%)	9/36 (25.00%)	2/20 (10.00%)
Weight increased † 1	0/84 (0.00%)	8/57 (14.04%)	3/36 (8.33%)	0/20 (0.00%)
Metabolism and nutrition disorders
Cell death † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	2/20 (10.00%)
Decreased appetite † 1	25/84 (29.76%)	17/57 (29.82%)	12/36 (33.33%)	6/20 (30.00%)
Dehydration † 1	5/84 (5.95%)	3/57 (5.26%)	2/36 (5.56%)	0/20 (0.00%)
Hyperglycaemia † 1	7/84 (8.33%)	4/57 (7.02%)	2/36 (5.56%)	2/20 (10.00%)
Hypoalbuminaemia † 1	3/84 (3.57%)	5/57 (8.77%)	1/36 (2.78%)	0/20 (0.00%)
Hypokalaemia † 1	5/84 (5.95%)	5/57 (8.77%)	3/36 (8.33%)	0/20 (0.00%)
Hypomagnesaemia † 1	3/84 (3.57%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Hyponatraemia † 1	3/84 (3.57%)	9/57 (15.79%)	4/36 (11.11%)	0/20 (0.00%)
Hypophosphataemia † 1	6/84 (7.14%)	5/57 (8.77%)	2/36 (5.56%)	1/20 (5.00%)
Vitamin D deficiency † 1	0/84 (0.00%)	1/57 (1.75%)	0/36 (0.00%)	2/20 (10.00%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	21/84 (25.00%)	17/57 (29.82%)	8/36 (22.22%)	8/20 (40.00%)
Back pain † 1	11/84 (13.10%)	6/57 (10.53%)	9/36 (25.00%)	3/20 (15.00%)
Groin pain † 1	0/84 (0.00%)	1/57 (1.75%)	1/36 (2.78%)	2/20 (10.00%)
Joint stiffness † 1	1/84 (1.19%)	0/57 (0.00%)	2/36 (5.56%)	0/20 (0.00%)
Muscle spasms † 1	2/84 (2.38%)	7/57 (12.28%)	5/36 (13.89%)	3/20 (15.00%)
Muscular weakness † 1	7/84 (8.33%)	1/57 (1.75%)	2/36 (5.56%)	1/20 (5.00%)
Musculoskeletal chest pain † 1	6/84 (7.14%)	4/57 (7.02%)	4/36 (11.11%)	2/20 (10.00%)
Myalgia † 1	10/84 (11.90%)	6/57 (10.53%)	4/36 (11.11%)	3/20 (15.00%)
Neck pain † 1	4/84 (4.76%)	3/57 (5.26%)	2/36 (5.56%)	3/20 (15.00%)
Pain in extremity † 1	17/84 (20.24%)	6/57 (10.53%)	4/36 (11.11%)	2/20 (10.00%)
Spinal osteoarthritis † 1	0/84 (0.00%)	0/57 (0.00%)	0/36 (0.00%)	2/20 (10.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acrochordon † 1	6/84 (7.14%)	1/57 (1.75%)	0/36 (0.00%)	0/20 (0.00%)
Basal cell carcinoma † 1	2/84 (2.38%)	2/57 (3.51%)	3/36 (8.33%)	0/20 (0.00%)
Keratoacanthoma † 1	6/84 (7.14%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Melanocytic naevus † 1	11/84 (13.10%)	2/57 (3.51%)	0/36 (0.00%)	1/20 (5.00%)
Seborrhoeic keratosis † 1	11/84 (13.10%)	1/57 (1.75%)	2/36 (5.56%)	2/20 (10.00%)
Skin papilloma † 1	26/84 (30.95%)	2/57 (3.51%)	1/36 (2.78%)	0/20 (0.00%)
Nervous system disorders
Dizziness † 1	8/84 (9.52%)	7/57 (12.28%)	9/36 (25.00%)	1/20 (5.00%)
Dysgeusia † 1	3/84 (3.57%)	5/57 (8.77%)	0/36 (0.00%)	0/20 (0.00%)
Headache † 1	17/84 (20.24%)	11/57 (19.30%)	8/36 (22.22%)	3/20 (15.00%)
Memory impairment † 1	2/84 (2.38%)	2/57 (3.51%)	1/36 (2.78%)	2/20 (10.00%)
Paraesthesia † 1	4/84 (4.76%)	3/57 (5.26%)	2/36 (5.56%)	0/20 (0.00%)
Sciatica † 1	0/84 (0.00%)	3/57 (5.26%)	1/36 (2.78%)	2/20 (10.00%)
Taste disorder † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Psychiatric disorders
Anxiety † 1	3/84 (3.57%)	2/57 (3.51%)	1/36 (2.78%)	3/20 (15.00%)
Confusional state † 1	2/84 (2.38%)	4/57 (7.02%)	1/36 (2.78%)	1/20 (5.00%)
Depression † 1	3/84 (3.57%)	3/57 (5.26%)	2/36 (5.56%)	2/20 (10.00%)
Insomnia † 1	7/84 (8.33%)	4/57 (7.02%)	5/36 (13.89%)	0/20 (0.00%)
Renal and urinary disorders
Urinary incontinence † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	27/84 (32.14%)	18/57 (31.58%)	10/36 (27.78%)	5/20 (25.00%)
Dysphonia † 1	9/84 (10.71%)	3/57 (5.26%)	5/36 (13.89%)	3/20 (15.00%)
Dyspnoea † 1	18/84 (21.43%)	15/57 (26.32%)	9/36 (25.00%)	3/20 (15.00%)
Epistaxis † 1	1/84 (1.19%)	4/57 (7.02%)	1/36 (2.78%)	0/20 (0.00%)
Haemoptysis † 1	8/84 (9.52%)	3/57 (5.26%)	2/36 (5.56%)	1/20 (5.00%)
Nasal congestion † 1	3/84 (3.57%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Oropharyngeal pain † 1	3/84 (3.57%)	3/57 (5.26%)	2/36 (5.56%)	1/20 (5.00%)
Pleural effusion † 1	0/84 (0.00%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Productive cough † 1	6/84 (7.14%)	7/57 (12.28%)	1/36 (2.78%)	1/20 (5.00%)
Pulmonary embolism † 1	0/84 (0.00%)	3/57 (5.26%)	3/36 (8.33%)	0/20 (0.00%)
Skin and subcutaneous tissue disorders
Acne † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	1/20 (5.00%)
Actinic keratosis † 1	11/84 (13.10%)	2/57 (3.51%)	3/36 (8.33%)	3/20 (15.00%)
Alopecia † 1	18/84 (21.43%)	6/57 (10.53%)	1/36 (2.78%)	0/20 (0.00%)
Dermal cyst † 1	3/84 (3.57%)	1/57 (1.75%)	3/36 (8.33%)	0/20 (0.00%)
Dry skin † 1	26/84 (30.95%)	22/57 (38.60%)	14/36 (38.89%)	2/20 (10.00%)
Eczema † 1	2/84 (2.38%)	3/57 (5.26%)	1/36 (2.78%)	2/20 (10.00%)
Erythema † 1	2/84 (2.38%)	7/57 (12.28%)	5/36 (13.89%)	4/20 (20.00%)
Erythema nodosum † 1	0/84 (0.00%)	3/57 (5.26%)	1/36 (2.78%)	1/20 (5.00%)
Hair texture abnormal † 1	7/84 (8.33%)	3/57 (5.26%)	0/36 (0.00%)	0/20 (0.00%)
Hyperhidrosis † 1	3/84 (3.57%)	4/57 (7.02%)	1/36 (2.78%)	1/20 (5.00%)
Hyperkeratosis † 1	26/84 (30.95%)	7/57 (12.28%)	1/36 (2.78%)	2/20 (10.00%)
Madarosis † 1	5/84 (5.95%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Palmar-plantar erythrodysaesthesia syndrome † 1	20/84 (23.81%)	2/57 (3.51%)	1/36 (2.78%)	0/20 (0.00%)
Papule † 1	11/84 (13.10%)	1/57 (1.75%)	1/36 (2.78%)	0/20 (0.00%)
Pruritus † 1	14/84 (16.67%)	9/57 (15.79%)	6/36 (16.67%)	2/20 (10.00%)
Rash † 1	15/84 (17.86%)	16/57 (28.07%)	11/36 (30.56%)	3/20 (15.00%)
Rash macular † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	0/20 (0.00%)
Rash maculo-papular † 1	5/84 (5.95%)	0/57 (0.00%)	0/36 (0.00%)	0/20 (0.00%)
Rash papular † 1	4/84 (4.76%)	2/57 (3.51%)	3/36 (8.33%)	0/20 (0.00%)
Seborrhoeic dermatitis † 1	0/84 (0.00%)	2/57 (3.51%)	2/36 (5.56%)	1/20 (5.00%)
Skin lesion † 1	4/84 (4.76%)	1/57 (1.75%)	4/36 (11.11%)	0/20 (0.00%)
Urticaria † 1	3/84 (3.57%)	3/57 (5.26%)	3/36 (8.33%)	0/20 (0.00%)
Vascular disorders
Haematoma † 1	1/84 (1.19%)	1/57 (1.75%)	2/36 (5.56%)	1/20 (5.00%)
Hypertension † 1	4/84 (4.76%)	6/57 (10.53%)	4/36 (11.11%)	4/20 (20.00%)
Hypotension † 1	6/84 (7.14%)	6/57 (10.53%)	5/36 (13.89%)	0/20 (0.00%)
Orthostatic hypotension † 1	0/84 (0.00%)	0/57 (0.00%)	2/36 (5.56%)	1/20 (5.00%)
1 Term from vocabulary, MedDRA (23.1); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

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

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.

Results Point of Contact

• Name/Title: Study Director
• Organization: Novartis Pharmaceuticals
• Phone: 862-778-8300
• EMail: Novartis.email@novartis.com

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

Schadendorf D, Robert C, Dummer R, Flaherty KT, Tawbi HA, Menzies AM, Banerjee H, Lau M, Long GV. Pyrexia in patients treated with dabrafenib plus trametinib across clinical trials in BRAF-mutant cancers. Eur J Cancer. 2021 Aug;153:234-241. doi: 10.1016/j.ejca.2021.05.005. Epub 2021 Jul 2.

Li J, Sasane M, Zhang J, Zhao J, Ricculli ML, Yao Z, Redhu S, Signorovitch J. Is time to progression associated with post-progression survival in previously treated metastatic non-small cell lung cancer with BRAF V600E mutation? A secondary analysis of phase II clinical trial data. BMJ Open. 2018 Aug 17;8(8):e021642. doi: 10.1136/bmjopen-2018-021642.

Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland A, Giannone V, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1307-1316. doi: 10.1016/S1470-2045(17)30679-4. Epub 2017 Sep 11.

Planchard D, Besse B, Groen HJM, Souquet PJ, Quoix E, Baik CS, Barlesi F, Kim TM, Mazieres J, Novello S, Rigas JR, Upalawanna A, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016 Jul;17(7):984-993. doi: 10.1016/S1470-2045(16)30146-2. Epub 2016 Jun 6.

Planchard D, Kim TM, Mazieres J, Quoix E, Riely G, Barlesi F, Souquet PJ, Smit EF, Groen HJ, Kelly RJ, Cho BC, Socinski MA, Pandite L, Nase C, Ma B, D'Amelio A Jr, Mookerjee B, Curtis CM Jr, Johnson BE. Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016 May;17(5):642-50. doi: 10.1016/S1470-2045(16)00077-2. Epub 2016 Apr 11.

• Responsible Party: Novartis ( Novartis Pharmaceuticals )
• ClinicalTrials.gov Identifier: NCT01336634
• Other Study ID Numbers: 113928; 2011-001161-41 ( EudraCT Number ); CDRB436E2201 ( Other Identifier: Novartis )
• First Submitted: April 7, 2011
• First Posted: April 18, 2011
• Results First Submitted: October 5, 2016
• Results First Posted: December 7, 2017
• Last Update Posted: April 4, 2022