Trial Outcomes & Findings for Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer (NCT NCT01723202)

Last Updated: 2025-08-24

Results Overview

The MR+PR+CR response rate will be estimated for each treatment arm. In determining this rate, the number of patients with RECIST-based MR, PR or CR will be divided by the number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true PR+CR response rate will be calculated.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

up to 24 weeks

Results posted on

2025-08-24

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A: Dabrafenib Alone Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)
Pre-crossover NOT COMPLETED	0	0
Pre-crossover STARTED	26	27
Pre-crossover COMPLETED	26	27
Post-Crossover of Arm A Patients STARTED	26	27
Post-Crossover of Arm A Patients Dabrafenib Alone	12	0
Post-Crossover of Arm A Patients Dabrafenib + Trametinib	14	27
Post-Crossover of Arm A Patients COMPLETED	26	27
Post-Crossover of Arm A Patients NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Dabrafenib With or Without Trametinib in Treating Patients With Advanced Differentiated Thyroid Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Total n=53 Participants Total of all reporting groups
Age, Continuous	60 years n=5 Participants	65 years n=7 Participants	62.5 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	20 Participants n=7 Participants	38 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	24 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	27 participants n=7 Participants	53 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 24 weeks

Population: Participants were analyzed for objective response rate prior to the crossover of Arm A patients to Dabrafenib + Trametinib.

Outcome measures

Outcome measures
Measure	Arm A: Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Cross-over to Dabrafenib + Trametinib Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Overall Objective Response Rate, Defined as the Proportion of Patients Who Have a Minor Response (MR), Partial Response (PR), or Complete Response(CR)Assessed According to RECIST.	42 percentage of participants Interval 23.0 to 63.0	48 percentage of participants Interval 29.0 to 68.0	—

SECONDARY outcome

Timeframe: Up to 4 years or from start of treatment to time of progression or death

Outcome measures

Outcome measures
Measure	Arm A: Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Cross-over to Dabrafenib + Trametinib n=14 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Progression-free Survival (PFS)	10.7 months Interval 3.8 to 34.7	15.1 months Interval 12.3 to 37.3	7.5 months Interval 2.8 to 38.5

SECONDARY outcome

Timeframe: up to 4 weeks after study treatment

The Kaplan-Meier method will be used to estimate overall survival. We will also evaluate the proportion of patients who are alive at one year.

Outcome measures

Outcome measures
Measure	Arm A: Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Cross-over to Dabrafenib + Trametinib n=14 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Overall Survival	37.9 months Interval 23.4 to Upper limit not reached due to insufficient number of participants with events	47.5 months Interval 27.9 to 57.8	36 months Interval 23.4 to Upper limit not reached due to insufficient number of participants with events

SECONDARY outcome

Timeframe: Every 2 weeks for the first 8 weeks, and then every 4-8 weeks thereafter up to 4 weeks after completion of study treatment, up to 1 year

Frequency and severity of adverse events in each of the treatment arms will be collected and summarized using descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described.

Outcome measures

Outcome measures
Measure	Arm A: Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Cross-over to Dabrafenib + Trametinib n=14 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Papulopustular rash	0 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Scalp pain	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Skin and subcutaneous tissue disorders - Other	17 number of events	9 number of events	2 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Flushing	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hot flashes	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypertension	2 number of events	4 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypotension	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Aortic valve disease	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Cardiac disorders - Other	0 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Blurred vision	0 number of events	4 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Floaters	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Retinal vascular disorder	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Colonic hemorrhage	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Duodenal hemorrhage	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Duodenal ulcer	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Gastroesophageal reflux disease	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Mucositis oral	0 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. General disorders and administration site conditions - Other	0 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Irritability	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Cholecysitis	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Fall	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Alanine aminotransferase increased	0 number of events	8 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Alkaline phosphatase increased	0 number of events	5 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Eye disorders - other	1 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Anemia	11 number of events	8 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Blood and lymphatic disorders- other	1 number of events	4 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Keratitis	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Sinus tachycardia	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypothyroidism	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dry Eye	1 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Photophobia	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Uveitis	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Abdominal distension	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Abdominal pain	3 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Constipation	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Diarrhea	4 number of events	7 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dry mouth	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dysphagia	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Gastric hemorrhage	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Gastric ulcer	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Gastrointestinal disorders - other	2 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Lower gastrointestinal hemorrhage	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Nausea	11 number of events	14 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Pancreatitis	2 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Vomiting	7 number of events	6 number of events	2 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Chills	11 number of events	14 number of events	4 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Edema limbs	3 number of events	5 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Fatigue	10 number of events	14 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Fever	13 number of events	16 number of events	6 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Flu like symptoms	2 number of events	4 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Non-cardiac chest pain	1 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Pain	2 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Rash acneiform	0 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Telangiectasia	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Thromboembolic even	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Thrombotic thrombocytopenic purpura	0 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Left ventricular systolic dysfunction	0 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Psychiatric disorders - Other	0 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Neutrophil count decreased	0 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypercalcemia	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypocalcemia	0 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Chest wall pain	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Depressed level of consciousness	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Memory impairment	0 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Paresthesia	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Peripheral sensory neuropathy	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Seizure	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Spasticity	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Urinary incontinence	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dysmenorrhea	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Epistaxis	0 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Erythema multiforme	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Urticaria	0 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hepatobiliary disorders - other	1 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Infections and infestations - other	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dermatitis radiation	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Aspartate aminotransferase increased	2 number of events	10 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Blood bilirubin increased	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Creatinine increased	1 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Ejection fraction decreased	3 number of events	1 number of events	2 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Electrocardiogram QT corrected interval prolonged	1 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Investigations - other	2 number of events	4 number of events	2 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Lipase increased	2 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Lymphocyte count decreased	5 number of events	4 number of events	3 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Platelet count decreased	3 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Weight loss	7 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. White blood cell decreased	2 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Anorexia	6 number of events	9 number of events	3 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hyperglycemia	12 number of events	5 number of events	5 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hyperkalemia	2 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypertriglyceridemia	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypoalbuminemia	2 number of events	2 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypokalemia	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hyponatremia	2 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hypophosphatemia	9 number of events	11 number of events	3 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Metabolism and nutrition disorders - other	1 number of events	3 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Arthralgia	6 number of events	3 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Arthritis	2 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Back pain	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Bone pain	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Generalized muscle weakness	1 number of events	5 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Muscle weakness upper limb	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Musculoskeletal and connective tissue disorder - Other	1 number of events	2 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Myalgia	5 number of events	6 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Neck pain	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Pain in extremity	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other	3 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Concentration impairment	1 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dizziness	3 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dysgeusia	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Encephalopathy	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Headache	5 number of events	3 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Nervous system disorders - Other	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Anxiety	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Confusion	1 number of events	1 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Urinary frequency	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Reproductive system and breast disorders - Other	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Cough	2 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dyspnea	1 number of events	2 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Hoarseness	2 number of events	1 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Productive cough	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Sore throat	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Alopecia	11 number of events	2 number of events	3 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Dry skin	1 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Nail ridging	1 number of events	0 number of events	1 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Palmar-plantar erythrodysesthesia syndrome	11 number of events	6 number of events	4 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Photosensitivity	1 number of events	0 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Pruritus	6 number of events	3 number of events	0 number of events
Number of Adverse Events Related to Treatment With GSK2118436 (BRAFi) as a Single Agent and Adverse Events Related to Treatment With GSK2118436 (BRAFi) and GSK1120212 (MEKi) in Combination. Rash maculo-papular	7 number of events	4 number of events	2 number of events

SECONDARY outcome

Timeframe: Every 2 weeks for the first 8 weeks, and then every 4-8 weeks thereafter up to 4 weeks after completion of study treatment, up to 1 year

Tolerability of the regimen in each of the treatment arms will be collected and summarized using descriptive statistics. We will also capture the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial. These tolerability measures will be assessed within each of the treatment arms and we will explore differences in these measures between the arms.

Outcome measures

Outcome measures
Measure	Arm A: Dabrafenib Alone n=26 Participants Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Cross-over to Dabrafenib + Trametinib n=14 Participants Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Tolerability of the Regimens in Terms of the Number of Patients Who Required Dose Modifications and/or Dose Delays. Dose Reductions	6 Participants	15 Participants	4 Participants
Tolerability of the Regimens in Terms of the Number of Patients Who Required Dose Modifications and/or Dose Delays. Permanent Discontinuations	5 Participants	6 Participants	2 Participants

Adverse Events

Arm A: Dabrafenib Alone

Serious events: 6 serious events

Other events: 26 other events

Deaths: 9 deaths

Arm B: Dabrafenib + Trametinib

Serious events: 6 serious events

Other events: 27 other events

Deaths: 8 deaths

Crossover to Dabrafenib + Trametinib

Serious events: 0 serious events

Other events: 14 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Dr. Bhavana Konda

The Ohio State University Comprehensive Cancer Center

Phone: 614-366-5068

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Arm A: Dabrafenib Alone n=26 participants at risk Patients receive dabrafenib orally 2 twice a day on days 1-28. Patients with disease progression may cross over to arm II. dabrafenib: 150 mg orally twice daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Arm B: Dabrafenib + Trametinib n=27 participants at risk Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally Correlative Studies: 1. Signaling inhibition studies in tumor biopsies (10 pts in each arm; 5 pts per center) 2. BRAF mutation studies in circulating plasma DNA (all study patients) 3. Mechanisms of drug resistance in tumor biopsies or tumor blocks (5 pts in each arm) 4. Assess predictors of response (Archival tumor block/unstained slides in all study patients) 5. Pharmacokinetic studies (First 10 pts enrolled on each arm) 6. Pharmacogenomics studies (All study patients)	Crossover to Dabrafenib + Trametinib n=14 participants at risk Patients receive dabrafenib orally twice a day and trametinib orally once a day on days 1-28. dabrafenib: 150 mg orally twice daily given orally trametinib: 150 mg orally twice daily and GSK1120212 (MEKi) 2 mg orally once daily given orally
Blood and lymphatic system disorders Anemia	7.7% 2/26 • Number of events 2 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Nervous system disorders Dysphagia	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Gastric hemorrhage	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Gastric Ulcer	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Pancreatitis	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
General disorders Fatigue	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Papillary urothelial carcinoma of the bladder	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Nervous system disorders Encephalopathy	3.8% 1/26 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/27 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
General disorders Fever	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	14.8% 4/27 • Number of events 6 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Cardiac disorders Cardiac disorders - Other	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Eye disorders Retinal vascular disorder	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Colonic hemorrhage	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Diarrhea	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Duodenal hemorrhage	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Duodenal ulcer	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Nausea	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Gastrointestinal disorders Vomiting	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
General disorders Chills	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Hepatobiliary disorders Cholecystitis	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Investigations Alanine aminotransferase increased	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Nervous system disorders Depressed level of consciousness	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Nervous system disorders Seizure	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.
Psychiatric disorders Confusion	0.00% 0/26 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	3.7% 1/27 • Number of events 1 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.	0.00% 0/14 • The severity of adverse events will be graded utilizing the National Cancer Institutes Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) up to 1 year. All-Cause Mortality was assessed up to 5 years.