Trial Outcomes & Findings for A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma (NCT NCT01584648)

Last Updated: 2021-02-17

Results Overview

PFS is defined as the interval between the date of randomization and the earliest date of PD or death due to any cause. PD was based on radiographic or photographic evidence, and assessments were made by the investigator according to RECIST, version 1.1. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm. The appearance of one or more new lesions, or the worsening of non-target lesions significant enough to require study treatment discontinuation, was also included as PD. Participants who received anti-cancer therapy prior to the date of documented events, were censored at the last adequate assessment prior to the initiation of therapy. If the participant did not have documented progression or death, PFS was censored at the date of the last adequate assessment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

423 participants

Primary outcome timeframe

From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)

Results posted on

2021-02-17

Participant Flow

This study was conducted in 103 centers in 14 countries worldwide: Argentina (1), Australia (6), Canada (5), France (8), Germany (25), Greece (3), Italy (8), Netherlands (3), Russia (4), Spain (7), Sweden (4), Ukraine (7), United Kingdom (10), and USA (12).

Approximately, 340 subjects were planned to be randomized in a 1:1 ratio (170 subjects each in combination therapy and monotherapy). A total of 423 subjects with unresectable or metastatic, BRAF V600E or V600K mutation-positive melanoma were randomized to dabrafenib and trametinib (n=211) or dabrafenib and placebo (n=212).

Participant milestones

Participant milestones
Measure	Dabrafenib + Trametinib Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.
Overall Study STARTED	211	212
Overall Study Safety Set	209	211
Overall Study Crossover Population	0	28
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	211	212

Reasons for withdrawal

Reasons for withdrawal
Measure	Dabrafenib + Trametinib Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.
Overall Study Death	136	146
Overall Study Lost to Follow-up	9	9
Overall Study Investigator discretion	3	2
Overall Study Withdrew consent	13	4
Overall Study Study closed/terminated	50	23
Overall Study Crossover to Dabrafenib + Trametinib	0	28

Baseline Characteristics

A Study Comparing Trametinib and Dabrafenib Combination Therapy to Dabrafenib Monotherapy in Subjects With BRAF-mutant Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabrafenib + Trametinib n=211 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=212 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Total n=423 Participants Total of all reporting groups
Age, Continuous	55.1 Years STANDARD_DEVIATION 13.33 • n=5 Participants	55.3 Years STANDARD_DEVIATION 13.75 • n=7 Participants	55.2 Years STANDARD_DEVIATION 13.52 • n=5 Participants
Sex: Female, Male Female	100 Participants n=5 Participants	98 Participants n=7 Participants	198 Participants n=5 Participants
Sex: Female, Male Male	111 Participants n=5 Participants	114 Participants n=7 Participants	225 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	211 Participants n=5 Participants	211 Participants n=7 Participants	422 Participants n=5 Participants

PRIMARY outcome

Timeframe: From randomization until the earliest date of disease progression (PD) or death due to any cause (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population was considered.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=211 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=212 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Progression-Free Survival (PFS) as Assessed by the Investigator	10.2 Months Interval 8.1 to 12.8	8.8 Months Interval 5.9 to 9.3	—

SECONDARY outcome

Timeframe: From the date of randomization until date of death due to any cause (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population was considered.

OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For the participants who did not die, overall survival was censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=211 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=212 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Overall Survival (OS)	25.8 Months Interval 19.2 to 38.2	18.7 Months Interval 15.2 to 23.1	—

SECONDARY outcome

Timeframe: From randomization until the first documented complete response or partial response (up to approximately 6 years)

Population: Intent-to-Treat (ITT) Population was considered. Only participants with measurable disease at Baseline per RECIST were analyzed.

ORR is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR). A participant was defined as a responder if he/she sustained a complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm). Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=210 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=210 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Objective Response Rate (ORR) as Assessed by the Investigator	146 Participants	113 Participants	—

SECONDARY outcome

Timeframe: From the time of the first documented response (CR or PR) until disease progression (up to approximately 6 years)

Population: ITT population. Only those participants with a confirmed CR or PR were analyzed (with or without measurabe disease at Baseline).

Duration of response is defined as the time from the first documented complete response (CR: the disappearance of all target lesions and any pathological lymph nodes must have a short axis of \<10 mm and the disappearance of all non-target lesions) or partial response (PR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters or the persistence of 1 or more non-target lesions or lymph nodes identified as a site of disease at Baseline with a short axis of ≥10mm) until disease progression (PD) or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters of target lesions with an absolute increase of at least 5mm or the appearance of one or more new lesions, or the worsening of non target lesions significant enough to require study treatment discontinuation. PD was based on the radiological evidence by investigator. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=146 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=114 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Duration of Response (DoR)	12.9 Months Interval 9.3 to 18.4	10.2 Months Interval 8.3 to 13.8	—

SECONDARY outcome

Timeframe: Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

Population: Pharmacokinetic (PK) Population: all participants included in the safety population for whom a PK sample was obtained and analyzed. Only participants with data available at the specified time points were analyzed.

Blood samples were collected for Pharmacokinetic (PK) analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=203 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=194 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Trametinib Pharmacokinetic Concentrations Week 8, pre-dose	9.9209 Nanogram per Milliliter (ng/mL) Standard Deviation 3.86587	0.0000 Nanogram per Milliliter (ng/mL) Standard Deviation 0.00000	—
Trametinib Pharmacokinetic Concentrations Week 8, 1-3 hours	19.0382 Nanogram per Milliliter (ng/mL) Standard Deviation 6.86542	0.0261 Nanogram per Milliliter (ng/mL) Standard Deviation 0.34598	—
Trametinib Pharmacokinetic Concentrations Week 8, 4-6 hours	16.7496 Nanogram per Milliliter (ng/mL) Standard Deviation 5.64363	0.0000 Nanogram per Milliliter (ng/mL) Standard Deviation 0.00000	—
Trametinib Pharmacokinetic Concentrations Week 16 pre-dose	11.0385 Nanogram per Milliliter (ng/mL) Standard Deviation 4.79185	0.0039 Nanogram per Milliliter (ng/mL) Standard Deviation 0.03548	—
Trametinib Pharmacokinetic Concentrations Week 24 pre-dose	11.5167 Nanogram per Milliliter (ng/mL) Standard Deviation 5.19171	0.0548 Nanogram per Milliliter (ng/mL) Standard Deviation 0.62447	—

SECONDARY outcome

Timeframe: Week 8 (0, 1-3, 4-6 hours post dose), Weeks 16 and 24 (0 hour pre-dose)

Population: PK Population.

Blood samples were collected for PK analysis in all participants. Three blood samples were collected at Week 8: pre-dose, 1-3 hours post dose, and 4-6 hours post dose. One pre-dose blood sample was obtained at Weeks 16 and 24. Plasma concentrations of Dabrafenib (GSK2118436) and its metabolites (Hydroxy-Dabrafenib (GSK2285403), Carboxy-Dabrafenib (GSK2298683), and Desmethyl-Dabrafenib (GSK2167542)) were determined using the currently approved analytical methodology. Only descriptive analysis performed.

Outcome measures

SECONDARY outcome

Timeframe: From the time the first dose of study treatment administered until 30 days after discontinuation of study treatment (up to approximately 6 years).

Population: Safety Population: all randomized participants who received at least one dose of study medication and were based on the actual treatment received if this differed from that to which the participant was randomized.

Analysis of absolute and relative frequencies for Adverse Event (AE) and Serious Adverse Event (SAE) by primary System Organ Class (SOC) to characterize the safety of dabrafenib and trametinib combination therapy through the monitoring of relevant clinical and laboratory safety parameters. In addition, new malignancies and AEs possibly related to study treatment were collected even if they occurred more than 30 days post-treatment. Only descriptive analysis performed.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=209 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=211 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib n=28 Participants Crossover Dabrafenib + Trametinib
Number of Participants With Adverse Events and Serious Adverse Events Adverse Event (AEs)	203 Participants	205 Participants	24 Participants
Number of Participants With Adverse Events and Serious Adverse Events Serious Adverse Event (SAEs)	100 Participants	80 Participants	8 Participants

POST_HOC outcome

Timeframe: up to 28 days before Day 1 (Screening), up to 77.4 months (on-treatment), up to approximately 6 years (study duration)

Population: Clinical database population; all treated patients and patients who died during screening.

Pre-treatment deaths were collected from screening visit up to the first day of treatment, for a maximum duration of 28 days. Patients who died during the screening period are considered as screen failure. On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 77.4 months (treatment duration ranged from 0.1 to 76.4 months). Deaths post treatment survival follow up were collected after the on- treatment period, up to approximately 6 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.

Outcome measures

Outcome measures
Measure	Dabrafenib + Trametinib n=210 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=211 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib n=28 Participants Crossover Dabrafenib + Trametinib
All Collected Deaths Post-treatment deaths	106 Participants	121 Participants	5 Participants
All Collected Deaths Pre-treatment deaths	1 Participants	0 Participants	0 Participants
All Collected Deaths On-treatment deaths	29 Participants	25 Participants	0 Participants
All Collected Deaths All deaths	136 Participants	146 Participants	5 Participants

Adverse Events

Dabrafenib + Trametinib

Serious events: 100 serious events

Other events: 194 other events

Deaths: 135 deaths

Dabrafenib + Placebo

Serious events: 80 serious events

Other events: 200 other events

Deaths: 146 deaths

Crossover Dabrafenib + Trametinib

Serious events: 8 serious events

Other events: 23 other events

Deaths: 5 deaths

All Patients

Serious events: 183 serious events

Other events: 394 other events

Deaths: 286 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Dabrafenib + Trametinib n=203 Participants Participants received dabrafenib 150 milligram (mg) HPMC capsules orally twice daily (BID), once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib 2 mg once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent.	Dabrafenib + Placebo n=194 Participants Participants received dabrafenib 150 mg HPMC capsules orally BID, once in the morning and a second dose approximately 12 hours after the morning dose, and trametinib placebo once daily in the morning. Treatment was continued until disease progression, death, unacceptable toxicity, or withdrawal of consent. Crossover to the combination therapy arm was allowed for subjects still receiving study treatment on the dabrafenib monotherapy arm after the positive result for the final OS analysis.	Crossover Dabrafenib + Trametinib Crossover Dabrafenib + Trametinib
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2118436, Week 8, pre-dose	92.1 Nanogram per Milliliter (ng/mL) Standard Deviation 204.85	64.4 Nanogram per Milliliter (ng/mL) Standard Deviation 96.98	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2118436, Week 8, 1-3 hours	1309.6 Nanogram per Milliliter (ng/mL) Standard Deviation 982.25	1362.3 Nanogram per Milliliter (ng/mL) Standard Deviation 992.97	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2118436, Week 8, 4-6 hours	458.9 Nanogram per Milliliter (ng/mL) Standard Deviation 318.59	539.7 Nanogram per Milliliter (ng/mL) Standard Deviation 553.09	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2118436, Week 16 pre-dose	151.6 Nanogram per Milliliter (ng/mL) Standard Deviation 261.31	151.02 Nanogram per Milliliter (ng/mL) Standard Deviation 381.32	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2118436, Week 24 pre-dose	167.0 Nanogram per Milliliter (ng/mL) Standard Deviation 346.97	156.5 Nanogram per Milliliter (ng/mL) Standard Deviation 357.50	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2285403, Week 8, pre-dose	346.6 Nanogram per Milliliter (ng/mL) Standard Deviation 261.73	308.9 Nanogram per Milliliter (ng/mL) Standard Deviation 224.56	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2285403, Week 8, 1-3 hours	361.7 Nanogram per Milliliter (ng/mL) Standard Deviation 245.92	341.8 Nanogram per Milliliter (ng/mL) Standard Deviation 240.96	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2285403, Week 8, 4-6 hours	316.9 Nanogram per Milliliter (ng/mL) Standard Deviation 208.51	328.1 Nanogram per Milliliter (ng/mL) Standard Deviation 234.95	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2285403, Week 16 pre-dose	335.0 Nanogram per Milliliter (ng/mL) Standard Deviation 228.26	331.0 Nanogram per Milliliter (ng/mL) Standard Deviation 250.04	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2285403, Week 24 pre-dose	306.2 Nanogram per Milliliter (ng/mL) Standard Deviation 203.77	312.8 Nanogram per Milliliter (ng/mL) Standard Deviation 250.28	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2298683, Week 8, pre-dose	82.0 Nanogram per Milliliter (ng/mL) Standard Deviation 123.93	76.7 Nanogram per Milliliter (ng/mL) Standard Deviation 109.09	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2298683,Week 8, 1-3 hours	648.5 Nanogram per Milliliter (ng/mL) Standard Deviation 459.01	672.7 Nanogram per Milliliter (ng/mL) Standard Deviation 519.45	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2298683, Week 8, 4-6 hours	391.3 Nanogram per Milliliter (ng/mL) Standard Deviation 206.70	502.2 Nanogram per Milliliter (ng/mL) Standard Deviation 356.72	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2298683, Week 16 pre-dose	128.7 Nanogram per Milliliter (ng/mL) Standard Deviation 174.26	121.1 Nanogram per Milliliter (ng/mL) Standard Deviation 195.15	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2298683,Week 24 pre-dose	126.1 Nanogram per Milliliter (ng/mL) Standard Deviation 219.82	145.7 Nanogram per Milliliter (ng/mL) Standard Deviation 265.57	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2167542, Week 8, pre-dose	3237.2 Nanogram per Milliliter (ng/mL) Standard Deviation 1694.66	3469.4 Nanogram per Milliliter (ng/mL) Standard Deviation 1854.02	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2167542, Week 8, 1-3 hours	4286.3 Nanogram per Milliliter (ng/mL) Standard Deviation 2514.50	4456.6 Nanogram per Milliliter (ng/mL) Standard Deviation 2687.32	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2167542, Week 8, 4-6 hours	6238.3 Nanogram per Milliliter (ng/mL) Standard Deviation 2716.05	6891.6 Nanogram per Milliliter (ng/mL) Standard Deviation 2739.07	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2167542, Week 16 pre-dose	3842.4 Nanogram per Milliliter (ng/mL) Standard Deviation 2428.74	4114.1 Nanogram per Milliliter (ng/mL) Standard Deviation 2432.72	—
Dabrafenib and Dabrafenib Metabolites (Hydroxy-, Carboxy- and Desmethyl-Dabrafenib) Concentrations GSK2167542, Week 24 pre-dose	3617.9 Nanogram per Milliliter (ng/mL) Standard Deviation 2645.51	4193.2 Nanogram per Milliliter (ng/mL) Standard Deviation 2730.78	—