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Japan PhI/II of GSK2118436 and GSK1120212 Combination in Subjects With BRAF V600E/K Mutation Positive Advanced Solid Tumors (Phase I Part) or Cutaneous Melanoma (Phase II Part)

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ClinicalTrials.gov Identifier: NCT01928940
Recruitment Status : Completed
First Posted : August 27, 2013
Results First Posted : October 2, 2015
Last Update Posted : July 24, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Tumours
Interventions Drug: dabrafenib
Drug: trametinib
Enrollment 12
Recruitment Details  
Pre-assignment Details This study consisted of 2 parts: Phase I part included Japanese participants (par.) with BRAF V600E/K mutation-positive advanced solid tumors and the Phase II part included Japanese par. with BRAF V600E/K mutation-positive cutaneous melanoma.
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal. In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Period Title: Overall Study
Started 6 6
Completed 6 5
Not Completed 0 1
Reason Not Completed
Adverse Event             0             1
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg Total
Hide Arm/Group Description In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal. In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal. Total of all reporting groups
Overall Number of Baseline Participants 6 6 12
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 6 participants 12 participants
52.2  (19.83) 59.0  (10.99) 55.6  (15.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 6 participants 12 participants
Female
5
  83.3%
2
  33.3%
7
  58.3%
Male
1
  16.7%
4
  66.7%
5
  41.7%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Asian - Japanese Heritage Number Analyzed 6 participants 6 participants 12 participants
6 6 12
1.Primary Outcome
Title Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)
Hide Description An AE is defined as any untoward medical occurrence (MO) in a part. temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. SAE is defined as any untoward MO that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect and protocol-specific SAEs:ALT>=3xupper limit of normal(ULN) and bilirubin>=2xULN(>35% direct) (or ALT>=3xULN, international normalized ratio>1.5), any new primary cancers, treatment emergent malignancies except basal cell carcinoma, symptomatic or asymptomatic LVEF decrease, retinal pigment epithelial detachment or retinal vein occlusion, pyrexia with hypotension,or dehydration or renal insufficiency,or severe (>=G3) rigor/chills.
Time Frame From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 year)
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Hide Analysis Population Description
All Treated Subject (ATS) Population: all participants who received at least one dose of study medication.
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Any AEs 6
Any SAEs 1
2.Primary Outcome
Title Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)
Hide Description A DLT was defined as an event occurred during the first 21 days after the first dose of study drugs and met any of the following criteria, according to National Cancer Institutes (NCI) common terminology criteria for AE (CTCAE) grade (G) version 4.0: G4 hematological toxicity; G3 or G4 non-hematologic toxicity (including rash, nausea, vomiting and diarrhea only if uncontrolled with supportive therapy); rash >=G3 that required dose reduction despite supportive care; a G2 or greater non-hematological toxicity that in the judgment of the investigator and medical monitor; dose interruption of greater than 14 consecutive days due to unresolved toxicity; any new G2 or greater valvular heart disease and significant alteration in cardiac valve morphology from Baseline.
Time Frame From the start of study treatment until 21 days
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Hide Analysis Population Description
DLT assessment Population: all participants for whom DLT assessment was appropriately conducted
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 5
Measure Type: Number
Unit of Measure: Participants
0
3.Primary Outcome
Title Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs)
Hide Description CCPs were graded according to NCI CTCAE grade version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters (para) for which an increase to G3 or G4 from BL G occurred. CCPs that were not G according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those para for which the category decreased to Low or increased to High relative to the BL category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. CCPs included: albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, calcium, creatinine, glucose, potassium, magnesium, sodium, inorganic phosphorus, chloride, lactate dehydrogenase (LDH), total protein, urea/blood urea nitrogen (BUN) and uric acid.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
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Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Alkaline Phosphatase, G3 1
ALT, G3 1
Inorganic Phosphorous, G4 1
Chloride, Low 2
LDH, Low 1
LDH, High 3
Total Protein, Low 2
Urea/BUN, Low 1
Urea/BUN, High 2
Uric acid, Low 1
Uric acid, High 1
4.Primary Outcome
Title Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters
Hide Description Hematology parameters were summarized according to NCI CTCAE G, version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline G occurred. For hematology parameters that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Hematology parameters included: hemoglobin, lymphocytes, total neutrophils, platelet count, white blood cell (WBC) counts, basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes and red blood cell (RBC) count.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Lymphocytes, G3 1
Total Neutrophils, G3 1
Basophils, High 1
Eosinophils, High 1
Hematocrit, Low 3
MCHC, Low 1
MCH, Low 2
MCV, Low 1
Monocytes, Low 2
Monocytes, High 3
RBC count, Low 4
5.Primary Outcome
Title Phase I: Number of Participants With the Indicated Urinalysis Parameters
Hide Description Urine samples were collected for urine dipstick analysis at Baseline and at the post-treatment Visit. The number of participants with negative (absence) and positive (presence: trace, 1+, 2+, 3+, 4+ or 5+) results for urine occult blood (UOB), urine glucose (UGLU), urine ketones (UKET), urine protein (UP) and urine urobilinogen (UUBIL) were summarized. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
UOB, Baseline, Negative 6
UOB, Baseline, Positive 0
UOB, Post-Treatment, Negative 2
UOB, Post-Treatment, Positive 1
UGLU, Baseline, Negative 6
UGLU, Baseline, Positive 0
UGLU, Post-Treatment, Negative 3
UGLU, Post-Treatment, Positive 0
UKET, Baseline, Negative 6
UKET, Baseline, Positive 0
UKET, Post-Treatment, Negative 3
UKET, Post-Treatment, Positive 0
UP, Baseline, Negative 5
UP, Baseline, Positive 1
UP, Post-Treatment, Negative 2
UP, Post-Treatment, Positive 0
UUBIL, Baseline, Negative 0
UUBIL, Baseline, Positive 6
UUBIL, Post-Treatment, Negative 0
UUBIL, Post-Treatment, Positive 3
6.Primary Outcome
Title Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status
Hide Description The ECOG pef status 5-point scale is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the par. and to determine appropriate treatment and prognosis: G0, fully active, able to carry on all pre-disease pef without restriction. G1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, example, light house work, office work. G2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about >50 percent (%) of waking hrs. G3, capable of only limited selfcare; confined to bed or chair >50% of waking hrs. G4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. G5, dead. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Number of par. who improved, had no change, or deteriorated in pef status from BL is summarized.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Improved 1
No change 4
Deteriorated 1
7.Primary Outcome
Title Phase I: Number of Participants With Worst-case On-therapy Increase From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3
Hide Description Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were graded using (NCI CTCAE version 4.0). SBP was categorized as: G1 (Increase to >=120 to 140 millimeters of mercury [mmHg]), G2 (Increase to >=140 to <160 mmHg), and G3 (Increase to >=160 mmHg). DBP was categorized as: G1 (Increase to >=80 to <90 mmHg), G2 (Increase to >=90 to <100 mmHg), and G3 (Increase to >=100 mmHg). The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of G0.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
SBP, Increase to Grade 2 3
SBP, Increase to Grade 3 0
DBP, Increase to Grade 2 2
DBP, Increase to Grade 3 1
8.Primary Outcome
Title Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate
Hide Description Change from Baseline in heart rate is categorized as decrease to <60 beats per minute (bpm), change to normal or no change, and increase to >100 bpm relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant's heart rate value decreased to <60 bpm and increased to >100 bpm post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Decrease to <60 bpm 1
Change to normal or no change 3
Increase to >100 bpm 3
9.Primary Outcome
Title Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature
Hide Description Change from Baseline in temperature is categorized as a decrease to <=35 degrees celsius (C), change to normal or no change as 35-38 degrees C, and increase to >=38 degrees C relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant temperature value decreased to <=35 degrees C and increased to >=38 degrees C post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Decrease to <=35 degrees C 2
Change to normal or no change 2
Increase to >=38 degrees C 3
10.Primary Outcome
Title Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points
Hide Description Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen,that is called as blood oxygen saturation or SpO2. Change from Baseline was calculated as the individual post-Baseline value (Days 8,15; Weeks 3 to 136 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Percentage of oxygen in blood
Day 8, n=6 1.0  (0.89)
Day 15, n=6 0.8  (0.75)
Week 3, n=6 0.2  (0.75)
Week 8, n=6 0.7  (1.21)
Week 12, n=5 1.4  (1.67)
Week 16, n=6 1.2  (2.14)
Week 20, n=5 0.4  (1.14)
Week 24, n=5 0.8  (1.92)
Week 28, n=5 0.8  (1.92)
Week 32, n=5 0.6  (1.14)
Week 36, n=5 0.8  (1.30)
Week 40, n=4 0.5  (1.00)
Week 44, n=4 0.5  (2.38)
Week 48, n=4 0.5  (2.08)
Week 52, n=2 -0.5  (2.12)
Week 56, n=2 0.0  (0.00)
Week 60, n=2 -0.5  (0.71)
Week 64, n=2 0.0  (0.00)
Week 68, n=1 0.0 [1]   (NA)
Week 72, n=1 1.0 [1]   (NA)
Week 76, n=1 0.0 [1]   (NA)
Week 80, n=1 1.0 [1]   (NA)
Week 84, n=1 0.0 [1]   (NA)
Week 88, n=1 0.0 [1]   (NA)
Week 92, n=1 -2.0 [1]   (NA)
Week 96, n=1 0.0 [1]   (NA)
Week 100, n=1 0.0 [1]   (NA)
Week 104, n=1 0.0 [1]   (NA)
Week 108, n=1 -1.0 [1]   (NA)
Week 112, n=1 0.0 [1]   (NA)
Week 116, n=1 0.0 [1]   (NA)
Week 120, n=1 0.0 [1]   (NA)
Week 124, n=1 0.0 [1]   (NA)
Week 128, n=1 0.0 [1]   (NA)
Week 132, n=1 0.0 [1]   (NA)
Week 136, n=1 0.0 [1]   (NA)
Post-Treatment, n=4 0.8  (0.96)
[1]
There were too few participants to provide a dispersion value.
11.Primary Outcome
Title Phase I: Change From Baseline in Weight at the Indicated Time Points
Hide Description Mean change in body weight from Baseline was determined. Change from Baseline was calculated as the individual post-Baseline value (Weeks 3 to 136 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit ( average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Kilogram (Kg)
Week 3, n=6 -4.87  (6.046)
Week 8, n=6 -4.43  (6.274)
Week 12, n=6 -4.13  (6.436)
Week 16, n=6 -4.00  (6.801)
Week 20, n=5 -0.62  (2.295)
Week 24, n=5 -0.70  (1.402)
Week 28, n=5 -0.36  (1.850)
Week 32, n=5 -0.38  (1.809)
Week 36, n=5 -0.78  (1.821)
Week 40, n=4 -1.43  (1.305)
Week 44, n=4 -0.68  (1.759)
Week 48, n=4 -1.03  (2.081)
Week 52, n=2 0.15  (2.475)
Week 56, n=2 -0.30  (1.556)
Week 60, n=2 -0.35  (2.475)
Week 64, n=2 -0.05  (2.475)
Week 68, n=1 -2.60 [1]   (NA)
Week 72, n=1 -2.10 [1]   (NA)
Week 76, n=1 -1.20 [1]   (NA)
Week 80, n=1 -0.70 [1]   (NA)
Week 84, n=1 -0.70 [1]   (NA)
Week 88, n=1 -1.20 [1]   (NA)
Week 92, n=1 -0.80 [1]   (NA)
Week 96, n=1 -0.80 [1]   (NA)
Week 100, n=1 -0.80 [1]   (NA)
Week 104, n=1 -0.50 [1]   (NA)
Week 108, n=1 -1.00 [1]   (NA)
Week 112, n=1 -1.00 [1]   (NA)
Week 116, n=1 -0.50 [1]   (NA)
Week 120, n=1 -0.60 [1]   (NA)
Week 124, n=1 -0.70 [1]   (NA)
Week 128, n=1 -0.60 [1]   (NA)
Week 132, n=1 -0.80 [1]   (NA)
Week 136, n=1 -0.50 [1]   (NA)
Post-Treatment, n=4 -0.05  (1.457)
[1]
There were too few participants to provide a dispersion value.
12.Primary Outcome
Title Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points
Hide Description Single twelve (12)-lead ECGs were perfomred at Baseline, Weeks 3 to 132 and post-treatment Visit. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 year)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Baseline, Normal, n=6 4
Baseline, Abnormal-NCS, n=6 2
Baseline, Abnormal-CS, n=6 0
Week 3, Normal, n=6 5
Week 3, Abnormal-NCS, n=6 1
Week 3, Abnormal-CS, n=6 0
Week 12, Normal, n=6 5
Week 12, Abnormal-NCS, n=6 1
Week 12, Abnormal-CS, n=6 0
Week 24, Normal, n=5 4
Week 24, Abnormal-NCS, n=5 1
Week 24, Abnormal-CS, n=5 0
Week 36, Normal, n=5 4
Week 36, Abnormal-NCS, n=5 1
Week 36, Abnormal-CS, n=5 0
Week 48, Normal, n=4 2
Week 48, Abnormal-NCS, n=4 2
Week 48, Abnormal-CS, n=4 0
Week 60, Normal, n=2 2
Week 60, Abnormal-NCS, n=2 0
Week 60, Abnormal-CS, n=2 0
Week 72, Normal, n=1 1
Week 72, Abnormal-NCS, n=1 0
Week 72, Abnormal-CS, n=1 0
Week 84, Normal, n=1 1
Week 84, Abnormal-NCS, n=1 0
Week 84, Abnormal-CS, n=1 0
Week 96, Normal, n=1 1
Week 96, Abnormal-NCS, n=1 0
Week 96, Abnormal-CS, n=1 0
Week 108, Normal, n=1 1
Week 108, Abnormal-NCS, n=1 0
Week 108, Abnormal-CS, n=1 0
Week 120, Normal, n=1 1
Week 120, Abnormal-NCS, n=1 0
Week 120, Abnormal-CS, n=1 0
Week 132, Normal, n=1 1
Week 132, Abnormal-NCS, n=1 0
Week 132, Abnormal-CS, n=1 0
Post-Treatment, Normal, n=3 3
Post-Treatment, Abnormal-NCS, n=3 0
Post-Treatment, Abnormal-CS, n=3 0
13.Primary Outcome
Title Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO)
Hide Description Absolute change from Baseline in LVEF were summarized at each scheduled assessment time and in the worst-case post Baseline. Only the post Baseline assessments that used the same method (ECHO or Multi Gated Acquisition Scan [MUGA]) as the Baseline assessments were used to derive the change from Baseline. The change from Baseline was categorized as: any increase; no change; 0-<10 Decrease, 10-19 Decrease, >=20 Decrease, >=10 Decrease and >= lower limit of normal (LLN), >=10 Decrease and below LLN, >=20 Decrease and >=LLN and >=20 Decrease and below LLN. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 milligrams (mg) (a combination of 75 mg capsules) orally twice daily (BID) and GSK1120212 2 mg tablet orally once daily (QD) until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hours (hr) after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial pharmacokinetic (PK) blood sampling. Study drugs were taken with approximately 200 milliliters (mL) of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Any Increase 0
No change 0
0-<10 Decrease 5
10-19 Decrease 1
>=20 Decrease 0
>=10 Decrease and >=LLN 1
>=10 Decrease and below LLN 0
>=20 Decrease and >=LLN 0
>=20 Decrease and below LLN 0
14.Primary Outcome
Title Phase II: Number of Participant With Confirmed Overall Response
Hide Description Confirmed overall response (ORR) is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). ORR was assessed by investigator and blinded independent central review (BICR).
Time Frame Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed 5
BICR-Assessed 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments For Investigator Assessed ORR
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments BICR Assessed ORR
15.Secondary Outcome
Title Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose
Hide Description Blood samples were collected from each par. at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr post-dose on Day 21 (repeat dose) for PK analysis. GSK2118436 metabolites included GSK2285403, GSK2298683, and GSK2167542. AUC from time zero to last quantifiable concentration (concn) (AUC[0-t]) was determined using the linear trapezoidal rule for increasing concn and the logarithmic trapezoidal rule for decreasing. The AUC from time zero extrapolated to infinity (AUC[0-inf] was calculated, where data permit, as the sum of AUC(0-t) and Ct/z, where Ct is the observed plasma concn obtained from the log-linear regression analysis of the last quantifiable time-point and z is the terminal phase rate constant. Area under the concentration-time curve over 12 hr and 24 hr dosing interval is called AUC[0-12] and AUC[0-24]. AUC(0-inf) was calculated only at Day 1.
Time Frame At pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr on Day 21 (repeat dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population: all par. included in the ATS population for whom a PK sample was obtained and analyzed. Only those par. available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hr*nanogram (ng)/mL
GSK2118436, AUC[0-t], Day 1, n=6
12850.5346
(37.3%)
GSK2118436, AUC[0-t], Day 21, n=6
10075.3530
(32.4%)
GSK2118436, AUC[0-12], Day 1, n=6
11414.9211
(41.3%)
GSK2118436, AUC[0-12], Day 21, n=6
10138.0887
(33.1%)
GSK2118436, AUC[0-inf], Day 1, n=6
13485.6357
(36.9%)
GSK2285403, AUC[0-t], Day 1, n=6
10530.0297
(39.4%)
GSK2285403, AUC[0-t], Day 21, n=6
7199.9862
(29.9%)
GSK2285403, AUC[0-12], Day 1, n=6
7929.4506
(64.3%)
GSK2285403, AUC[0-12], Day 21, n=6
7273.0445
(30.6%)
GSK2285403, AUC[0-inf], Day 1, n=6
13903.4979
(67.9%)
GSK2298683, AUC[0-t], day 1, n=6
50834.2106
(106.0%)
GSK2298683, AUC[0-t], Day 21, n=6
108578.495
(36.1%)
GSK2298683, AUC[0-12], Day 1, n=6
18963.4767
(255.7%)
GSK2298683, AUC[0-12], Day 21, n=6
113205.044
(36.8%)
GSK2298683, AUC[0-inf], Day 1, n=5
125748.810
(41.8%)
GSK2167542, AUC[0-t], Day 1, n=6
571.5619
(170.4%)
GSK2167542, AUC[0-t], Day 21, n=6
2503.0667
(92.7%)
GSK2167542, AUC[0-12], Day 1, n=6
116.1860
(269.6%)
GSK2167542, AUC[0-12], Day 21, n=4
2755.2522
(122.0%)
GSK2167542, AUC[0-inf], Day 1, n=1
4628.4351 [1] 
(NA%)
GSK1120212, AUC[0-t], Day 1, n=6
69.3090
(50.2%)
GSK1120212, AUC[0-t], Day 21, n=6
261.2787
(20.9%)
GSK1120212, AUC[0-24], Day 1, n=5
82.5215
(23.1%)
GSK1120212, AUC[0-24], Day 21, n=6
447.9452
(25.5%)
GSK1120212, AUC[0-inf], Day 1, n=5
375.5275
(23.1%)
[1]
There were too few participants to provide a dispersion value
16.Secondary Outcome
Title Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose
Hide Description Blood samples were collected from each participant at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr post-dose on Day 21 (repeat dose) for PK analysis. GSK2118436 metabolites included GSK2285403, GSK2298683 and GSK2167542. Cmax was determined from the raw concentration-time data.
Time Frame At pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr on Day 21 (repeat dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
GSK2118436, Day 1
2497.383
(69.7%)
GSK2118436, Day 21
3431.280
(12.0%)
GSK2285403, Day 1
1336.296
(70.1%)
GSK2285403, Day 21
1995.847
(14.8%)
GSK2298683, Day 1
3689.039
(75.5%)
GSK2298683, Day 21
12303.403
(32.5%)
GSK2167542, Day 1
50.405
(149.7%)
GSK2167542, Day 21
323.863
(82.4%)
GSK1120212, Day 1
7.824
(112.1%)
GSK1120212, Day 21
32.522
(20.2%)
17.Secondary Outcome
Title Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose
Hide Description Trough concentration is the lowest level that a drug is present in the body. Pre-dose (trough) blood samples were collected on Day 8, Day 15, Weeks 3, 8, 16 and 24 for estimating plasma trough concentration. GSK2118436 metabolites included GSK2285403, GSK2298683, and GSK2167542. Ctau was determined from the raw concentration-time data.
Time Frame At pre-dose on Day 8, Day 15, Weeks 3, 8, 16 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
GSK2118436, Day 8, n=6
118.36
(188.3%)
GSK2118436, Day 15, n=6
84.25
(136.2%)
GSK2118436, Week 3, n=6
78.14
(149.3%)
GSK2118436, Week 8, n=6
78.29
(591.4%)
GSK2118436, Week 16, n=6
105.05
(206.4%)
GSK2118436, Week 24, n=5
121.85
(183.9%)
GSK2285403, Day 8, n=6
149.61
(111.9%)
GSK2285403, Day 15, n=6
106.09
(72.8%)
GSK2285403, Week 3, n=6
93.87
(82.0%)
GSK2285403, Week 8, n=6
89.12
(239.4%)
GSK2285403, Week 16, n=6
100.10
(121.8%)
GSK2285403, Week 24, n=5
117.93
(121.4%)
GSK2298683, Day 8, n=6
6011.00
(39.8%)
GSK2298683, Day 15, n=6
5141.38
(39.5%)
GSK2298683, Week 3, n=6
6210.90
(51.8%)
GSK2298683, Week 8, n=6
4408.24
(65.0%)
GSK2298683, Week 16, n=6
4022.93
(39.4%)
GSK2298683, Week 24, n=5
4294.86
(51.9%)
GSK2167542, Day 8, n=6
217.73
(46.7%)
GSK2167542, Day 15, n=6
161.11
(107.5%)
GSK2167542, Week 3, n=6
224.32
(83.6%)
GSK2167542, Week 8, n=6
220.93
(52.2%)
GSK2167542, Week 16, n=6
270.15
(107.5%)
GSK2167542, Week 24, n=5
227.75
(101.5%)
GSK1120212, Day 8, n=6
11.36
(43.0%)
GSK1120212, Day 15, n=6
12.47
(22.4%)
GSK1120212, Week 3, n=6
13.80
(25.6%)
GSK1120212, Week 8, n=6
14.52
(65.0%)
GSK1120212, Week 16, n=6
13.47
(39.4%)
GSK1120212, Week 24, n=5
13.72
(41.3%)
18.Secondary Outcome
Title Phase I: Time of Occurrence of Cmax (Tmax) and Terminal Phase Half Life (t1/2) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose
Hide Description Blood samples were collected from each participant at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr post-dose on Day 21 (repeat dose) for PK analysis. GSK2118436 metabolites included GSK2285403, GSK2298683, and GSK2167542. Tmax is defined as the time of occurrence of Cmax. Tmax was determined directly from the raw concentration-time data. The apparent terminal elimination half-life (t1/2) obtained as the ratio of ln2/lamdaz, where lamdaz is the terminal phase rate constant estimated by linear regression analysis of the log transformed concentration-time data. . T1/2 was calculated only at Day 1.
Time Frame At pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr on Day 21 (repeat dose)
Hide Outcome Measure Data
Hide Analysis Population Description
PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: hr
GSK2118436, t1/2, Day 1, n=6
4.5398
(2.776 to 9.645)
GSK2118436, tmax, Day 1, n=6
2.425
(1.43 to 3.85)
GSK2118436, tmax, Day 21, n=6
1.685
(0.97 to 1.97)
GSK2285403, t1/2, Day 1, n=6
4.2086
(3.574 to 55.294)
GSK2285403, tmax, Day 1, n=6
3.410
(2.93 to 11.93)
GSK2285403, tmax, Day 21, n=6
1.950
(1.47 to 2.93)
GSK2298683, t1/2, Day 1, n=5
15.5414
(11.652 to 21.159)
GSK2298683, tmax, Day 1, n=6
9.840
(7.92 to 23.82)
GSK2298683, tmax, Day 21, n=6
4.955
(2.75 to 5.98)
GSK2167542, t1/2, Day 1, n=1
55.8643
(55.8643 to 55.8643)
GSK2167542, tmax, Day 1, n=6
23.885
(11.65 to 24.28)
GSK2167542, tmax, Day 21, n=6
4.505
(1.97 to 9.92)
GSK1120212, t1/2, Day 1, n=5
89.5954
(39.029 to 126.331)
GSK1120212, tmax, Day 1, n=6
0.965
(0.92 to 23.82)
GSK1120212, tmax, Day 21, n=6
1.210
(0.92 to 5.93)
19.Secondary Outcome
Title Phase I: Number of Participants With Confirmed Overall Response Rate
Hide Description Confirmed ORR is defined as the percentage of participants with a confirmed CR or PR according to RECIST, version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). ORR was assessed by investigator and BICR.
Time Frame Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed 5
BICR-Assessed 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments For Investigator Assessed ORR
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0158
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 50
Confidence Interval (2-Sided) 95%
11.8 to 82.2
Estimation Comments BICR Assessed ORR
20.Secondary Outcome
Title Phase I: Number of Participants With Unconfirmed Overall Response Rate
Hide Description ORR is defined as the percentage of participants with an unconfirmed CR or PR according to RECIST version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. CR is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). Unconfirmed ORR was assessed by investigator and BICR.
Time Frame Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed 5
BICR-Assessed 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments For Investigator Assessed ORR
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0158
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 50
Confidence Interval (2-Sided) 95%
11.8 to 88.2
Estimation Comments BICR Assessed ORR
21.Secondary Outcome
Title Phase I: Progression Free Survival (PFS)
Hide Description PFS is defined as the time from the first dose of study treatment to the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or disease progression minus the date of first dose plus one day. The date of documented disease progression is defined as the date of disease progression based on radiologic evidence. Participants with documented date of disease progresssion or death and who had not received subsequent anticancer treatment prior to the date of documented disease progression or death were included in the analysis of PFS. PFS was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.
Time Frame From start of the treatment until disease progression or death (average of 1.38 years)
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Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ATS population.
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: Weeks
Investigator-Assessed, n=6
NA [1] 
(16 to 65.1)
BICR-Assessed, n=6
NA [1] 
(9 to 65.1)
[1]
The median values were not planned to calculate in the study analysis plan because lack of events had been estimated at the time of this primary analysis of the ORR.
22.Secondary Outcome
Title Phase I: Duration of Response
Hide Description Duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause among participants with confirmed CR or PR. The participant who showed a CR or PR was included in the analysis of duration of response. Duration of response was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.
Time Frame From start of the treatment until disease progression or death (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ATS population.
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: Weeks
Investigator-Assessed, n=5
NA [1] 
(17.4 to 57.1)
BICR-Assessed, n=3
NA [1] 
(32.1 to 57.1)
[1]
The median values were not planned to calculate in the study analysis plan because lack of events had been estimated at the time of this primary analysis of the ORR.
23.Secondary Outcome
Title Phase II: Number of Participants With Unconfirmed Overall Response
Hide Description ORR is defined as the percentage of participants with an unconfirmed CR or PR according to RECIST version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment. CR is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). Unconfirmed ORR was assessed by investigator and BICR.
Time Frame Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)
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ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Investigator-Assessed 5
BICR-Assessed 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments For Investigator Assessed ORR
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Exact binomial test
Comments [Not Specified]
Method of Estimation Estimation Parameter Percentage
Estimated Value 83
Confidence Interval (2-Sided) 95%
35.9 to 99.6
Estimation Comments BICR Assessed ORR
24.Secondary Outcome
Title Phase II: Progression Free Survival (PFS)
Hide Description PFS is defined as the time from the first dose of study treatment to the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or disease progression minus the date of first dose plus one day. The date of documented disease progression is defined as the date of disease progression based on radiologic evidence. Participants with documented date of disease progresssion or death and who had not received subsequent anticancer treatment prior to the date of documented disease progression or death were included in the analysis of PFS. PFS was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.
Time Frame From start of the treatment until disease progression or death (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ATS population.
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: Weeks
Investigator-Assessed, n=6
NA [1] 
(19.0 to 128.4)
BICR-Assessed, n=6
NA [1] 
(19.0 to 128.4)
[1]
The median values were not planned to calculate in the study analysis plan because lack of events had been estimated at the time of this primary analysis of the ORR.
25.Secondary Outcome
Title Phase II: Duration of Response
Hide Description Duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause among participants with confirmed CR or PR. The participant who showed a CR or PR was included in the analysis of duration of response. Duration of response was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.
Time Frame From start of the treatment until disease progression or death (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ATS population.
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Median (Full Range)
Unit of Measure: Weeks
Investigator-Assessed, n=5
NA [1] 
(16 to 120.1)
BICR-Assessed, n=5
NA [1] 
(11.1 to 120.1)
[1]
There were too few participants to provide a median PFS
26.Secondary Outcome
Title Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event
Hide Description An AE is defined as any untoward MO in a part. temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. SAE is defined as any untoward MO that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect and protocol-specific SAEs:ALT>=3xULN and bilirubin>=2xULN(>35% direct) (or ALT>=3xULN, international normalized ratio>1.5), any new primary cancers, treatment emergent malignancies except basal cell carcinoma, symptomatic or asymptomatic LVEF decrease, retinal pigment epithelial detachment or retinal vein occlusion, pyrexia with hypotension,or dehydration or renal insufficiency,or severe (>=G3) rigor/chills.
Time Frame From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 years)
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Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Any AE 6
Any SAE 0
27.Secondary Outcome
Title Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters
Hide Description CCPs were graded according to NCI CTCAE garde version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline grade occurred. CCPs that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. CCPs included: albumin, alkaline phosphatase, ALT, AST, total bilirubin, calcium, creatinine, glucose, potassium, magnesium, sodium, inorganic phosphorus, chloride, LDH, total protein, urea/BUN and uric acid.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Inorganic Phosphorous, G3 2
Chloride, High 2
LDH, High 5
Total Protein, Low 2
Urea/BUN, High 1
Uric acid, Low 1
28.Secondary Outcome
Title Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters
Hide Description Hematology parameters were summarized according to NCI CTCAE G, version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline G occurred. For hematology parameters that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Hematology parameters included: hemoglobin, lymphocytes, total neutrophils, platelet count, WBC counts, basophils, eosinophils, hematocrit, MCHC, MCH, MCV, monocytes and RBC count.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Total Neutrophils, G3 1
Eosinophils, High 1
Hematocrit, Low 2
MCHC, Low 1
MCH, Low 1
MCV, Low 1
MCV, High 1
Monocytes, Low 3
Monocytes, High 4
RBC count, Low 1
RBC count, High 1
29.Secondary Outcome
Title Phase II: Number of Participants With the Indicated Urinalysis Results
Hide Description Urine samples were collected for urine dipstick analysis at Baseline and at the post-treatment Visit. The number of participants with negative (absence) and positive (presence: trace, 1+, 2+, 3+, 4+ or 5+) results for UOB, UGLU, UKET, UP and UUBIL were summarized. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
UOB, Baseline, Negative 6
UOB, Baseline, Positive 0
UOB, Post-Treatment, Negative 3
UOB, Post-Treatment, Positive 0
UGLU, Baseline, Negative 6
UGLU, Baseline, Positive 0
UGLU, Post-Treatment, Negative 2
UGLU, Post-Treatment, Positive 1
UKET, Baseline, Negative 5
UKET, Baseline, Positive 1
UKET, Post-Treatment, Negative 2
UKET, Post-Treatment, Positive 1
UP, Baseline, Negative 6
UP, Baseline, Positive 0
UP, Post-Treatment, Negative 2
UP, Post-Treatment, Positive 1
UUBIL, Baseline, Negative 0
UUBIL, Baseline, Positive 6
UUBIL, Post-Treatment, Negative 0
UUBIL, Post-Treatment, Positive 3
30.Secondary Outcome
Title Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status
Hide Description The ECOG pef status 5-point scale is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the par. and to determine appropriate treatment and prognosis: G0, fully active, able to carry on all pre-disease pef without restriction. G1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, example, light house work, office work. G2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about >50% of waking hrs. G3, capable of only limited selfcare; confined to bed or chair >50% of waking hrs. G4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. G5, dead. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Number of par. who improved, had no change, or deteriorated in pef status from BL is summarized.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Improved 0
No change 4
Deteriorated 2
31.Secondary Outcome
Title Phase II: Number of Participants With Worst-case On-therapy Increase From Baseline in Systolic and Diastolic Blood Pressure to Grade 2 or Grade 3
Hide Description SBP and DBP values were graded using (NCI CTCAE version 4.0). SBP was categorized as: G1 (Increase to >=120 to 140 mmHg), G2 (Increase to >=140 to <160 mmHg), and G3 (Increase to >=160 mmHg). DBP was categorized as: G1 (Increase to >=80 to <90 mmHg), G2 (Increase to >=90 to <100 mmHg), and G3 (Increase to >=100 mmHg). The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of G0.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
SBP, Increase to Grade 2 3
SBP, Increase to Grade 3 0
DBP, Increase to Grade 2 5
DBP, Increase to Grade 3 0
32.Secondary Outcome
Title Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate
Hide Description Change from Baseline in heart rate is categorized as decrease to <60 bpm, change to normal or no change, and increase to >100 bpm relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant's heart rate value decreased to <60 bpm and increased to >100 bpm post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Decrease to <60 bpm 1
Change to normal or no change 4
Increase to >100 bpm 1
33.Secondary Outcome
Title Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature
Hide Description Change from Baseline in temperature is categorized as a decrease to <=35 degrees C, change to normal or no change as 35-38 degrees C, and increase to >=38 degrees C relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant temperature value decreased to <=35 degrees C and increased to >=38 degrees C post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Decrease to <=35 degrees C 2
Change to normal or no change 4
Increase to >=38 degrees C 0
34.Secondary Outcome
Title Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points
Hide Description Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation, or SpO2. Change from Baseline was calculated as the individual post-Baseline value (Days 8 and 15; Weeks 3 to 132 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Percentage of oxygen in blood
Day 8, n=6 -0.2  (0.98)
Day 15, n=6 0.3  (1.51)
Week 3, n=6 0.5  (0.84)
Week 8, n=6 0.5  (1.05)
Week 12, n=6 -0.2  (0.98)
Week 16, n=6 0.3  (1.51)
Week 20, n=5 -1.0  (1.58)
Week 24, n=5 0.2  (1.64)
Week 28, n=5 -0.2  (0.84)
Week 32, n=5 -0.6  (1.14)
Week 36, n=5 -0.4  (1.34)
Week 40, n=5 0.0  (1.58)
Week 44, n=4 -1.3  (2.22)
Week 48, n=4 1.0  (1.41)
Week 52, n=3 1.0  (1.73)
Week 56, n=3 -0.7  (0.58)
Week 60, n=3 -0.3  (1.15)
Week 64, n=3 -0.3  (0.58)
Week 68, n=3 0.0  (1.00)
Week 72, n=3 -0.7  (1.53)
Week 76, n=3 -1.0  (0.00)
Week 80, n=3 0.0  (1.00)
Week 84, n=3 -0.3  (1.53)
Week 88, n=3 -0.3  (1.53)
Week 92, n=3 0.3  (0.58)
Week 96, n=3 -0.3  (0.58)
Week 100, n=3 -0.7  (1.15)
Week 104, n=3 -0.3  (1.53)
Week 108, n=3 0.0  (1.00)
Week 112, n=3 0.0  (1.00)
Week 116, n=3 -0.7  (0.58)
Week 120, n=2 -0.5  (0.71)
Week 124, n=1 -2.0 [1]   (NA)
Week 128, n=1 1.0 [1]   (NA)
Week 132, n=1 -2.0 [1]   (NA)
Post-Treatment, n=3 1.3  (0.58)
[1]
There were too few participants to provide a dispersion value.
35.Secondary Outcome
Title Phase II: Change From Baseline in Weight at the Indicated Time Points
Hide Description Mean change in body weight from baseline was determined. Change from Baseline was calculated as the individual post-Baseline value (Weeks 3 to 132 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: Kg
Week 3, n=6 -0.68  (0.538)
Week 8, n=6 -0.22  (0.553)
Week 12, n=6 -0.30  (1.273)
Week 16, n=6 0.05  (1.947)
Week 20, n=5 -0.32  (2.318)
Week 24, n=5 0.06  (2.243)
Week 28, n=5 0.18  (2.500)
Week 32, n=5 0.42  (2.607)
Week 36, n=5 0.98  (3.016)
Week 40, n=5 0.62  (2.734)
Week 44, n=4 0.80  (3.790)
Week 48, n=4 0.68  (3.527)
Week 52, n=3 1.27  (3.993)
Week 56, n=3 2.23  (3.932)
Week 60, n=3 2.83  (3.879)
Week 64, n=3 2.70  (4.246)
Week 68, n=3 2.87  (4.143)
Week 72, n=3 2.87  (4.165)
Week 76, n=3 3.63  (2.793)
Week 80, n=3 3.43  (4.007)
Week 84, n=3 4.37  (4.008)
Week 88, n=3 3.80  (3.905)
Week 92, n=3 4.13  (3.496)
Week 96, n=3 4.13  (3.630)
Week 100, n=3 3.53  (3.219)
Week 104, n=3 4.00  (4.557)
Week 108, n=3 3.93  (4.800)
Week 112, n=3 3.60  (4.649)
Week 116, n=3 4.20  (4.859)
Week 120, n=2 5.95  (2.192)
Week 124, n=1 7.50 [1]   (NA)
Week 128, n=1 5.80 [1]   (NA)
Week 132, n=1 5.30 [1]   (NA)
Post-Treatment, n=3 0.13  (2.155)
[1]
There were too few participants to provide a dispersion value.
36.Secondary Outcome
Title Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points
Hide Description Single 12-lead ECGs were performed at Baseline, Weeks 3 to 132 and post-treatment Visit. ECG findings were categorized as: normal, abnormal - CS, or abnormal - NCS, as determined by the investigator.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Baseline, Normal, n=6 5
Baseline, Abnormal-NCS, n=6 1
Baseline, Abnormal-CS, n=6 0
Week 3, Normal, n=6 4
Week 3, Abnormal-NCS, n=6 2
Week 3, Abnormal-CS, n=6 0
Week 12, Normal, n=6 4
Week 12, Abnormal-NCS, n=6 2
Week 12, Abnormal-CS, n=6 0
Week 24, Normal, n=5 3
Week 24, Abnormal-NCS, n=5 2
Week 24, Abnormal-CS, n=5 0
Week 36, Normal, n=5 2
Week 36, Abnormal-NCS, n=5 3
Week 36, Abnormal-CS, n=5 0
Week 48, Normal, n=4 3
Week 48, Abnormal-NCS, n=4 1
Week 48, Abnormal-CS, n=4 0
Week 60, Normal, n=3 2
Week 60, Abnormal-NCS, n=3 1
Week 60, Abnormal-CS, n=3 0
Week 72, Normal, n=3 2
Week 72, Abnormal-NCS, n=3 1
Week 72, Abnormal-CS, n=3 0
Week 84, Normal, n=3 1
Week 84, Abnormal-NCS, n=3 2
Week 84, Abnormal-CS, n=3 0
Week 96, Normal, n=3 1
Week 96, Abnormal-NCS, n=3 2
Week 96, Abnormal-CS, n=3 0
Week 108, Normal, n=3 1
Week 108, Abnormal-NCS, n=3 2
Week 108, Abnormal-CS, n=3 0
Week 120, Normal, n=2 1
Week 120, Abnormal-NCS, n=2 1
Week 120, Abnormal-CS, n=2 0
Week 132, Normal, n=1 0
Week 132, Abnormal-NCS, n=1 1
Week 132, Abnormal-CS, n=1 0
Post-Treatment, Normal, n=3 3
Post-Treatment, Abnormal-NCS, n=3 0
Post-Treatment, Abnormal-CS, n=3 0
37.Secondary Outcome
Title Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram
Hide Description Absolute change from Baseline in LVEF were summarized at each scheduled assessment time and in the worst-case post Baseline. Only the post Baseline assessments that used the same method (ECHO or MUGA) as the Baseline assessments were used to derive the change from Baseline. The change from Baseline was categorized as: any increase; no change; 0-<10 Decrease, 10-19 Decrease, >=20 Decrease, >=10 Decrease and >= LLN, >=10 Decrease and below LLN, >=20 Decrease and >=LLN and >=20 Decrease and below LLN. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.
Time Frame From Baseline until the post-treatment Visit (average of 1.38 years)
Hide Outcome Measure Data
Hide Analysis Population Description
ATS Population
Arm/Group Title Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description:
In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
Overall Number of Participants Analyzed 6
Measure Type: Number
Unit of Measure: Participants
Any Increase 1
No change 0
0-<10 Decrease 3
10-19 Decrease 2
>=20 Decrease 0
>=10 Decrease and >=LLN 2
>=10 Decrease and below LLN 0
>=20 Decrease and >=LLN 0
>=20 Decrease and below LLN 0
Time Frame On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product (IP) until 30 days after the last dose of IP (average of 1.38 years).
Adverse Event Reporting Description SAEs and non-serious AEs were reported for members of the All Treated Subjects (ATS) population, comprised of all participants who had received at least one dose of IP.
 
Arm/Group Title Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Hide Arm/Group Description In the Phase I part, participants with BRAF V600E/K mutation-positive advanced solid tumors received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. The second dose of GSK2118436 was not administered on Day 1 for the 24 hr serial PK blood sampling. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal. In the Phase II part, participants with BRAF V600E/K mutation-positive cutaneous melanoma received the combination therapy of GSK2118436 150 mg (a combination of 75 mg capsules) orally BID and GSK1120212 2 mg tablet orally QD until disease progression, death or an unacceptable adverse event. GSK2118436 and GSK1120212 were administered in the morning at approximately the same time. The second dose of GSK2118436 was taken in the evening approximately 12 hr after the morning dose. Study drugs were taken with approximately 200 mL of water under fasting conditions, either 1 hr before or 2 hr after a meal.
All-Cause Mortality
Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   1/6 (16.67%)   0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonitis  1  1/6 (16.67%)  0/6 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase I: GSK2118436 150 mg + GSK1120212 2 mg Phase II: GSK2118436 150 mg + GSK1120212 2 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   6/6 (100.00%)   6/6 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  0/6 (0.00%)  2/6 (33.33%) 
Neutropenia  1  0/6 (0.00%)  3/6 (50.00%) 
Leukopenia  1  0/6 (0.00%)  1/6 (16.67%) 
Cardiac disorders     
Mitral valve incompetence  1  0/6 (0.00%)  1/6 (16.67%) 
Ear and labyrinth disorders     
Deafness neurosensory  1  0/6 (0.00%)  1/6 (16.67%) 
Eye disorders     
Retinal detachment  1  0/6 (0.00%)  1/6 (16.67%) 
Uveitis  1  0/6 (0.00%)  1/6 (16.67%) 
Visual impairment  1  1/6 (16.67%)  0/6 (0.00%) 
Retinal vascular disorder  1  0/6 (0.00%)  1/6 (16.67%) 
Gastrointestinal disorders     
Stomatitis  1  2/6 (33.33%)  3/6 (50.00%) 
Constipation  1  1/6 (16.67%)  2/6 (33.33%) 
Nausea  1  2/6 (33.33%)  1/6 (16.67%) 
Vomiting  1  2/6 (33.33%)  1/6 (16.67%) 
Cheilitis  1  1/6 (16.67%)  0/6 (0.00%) 
Dental caries  1  0/6 (0.00%)  1/6 (16.67%) 
Dental caries  1  1/6 (16.67%)  0/6 (0.00%) 
Diarrhoea  1  0/6 (0.00%)  1/6 (16.67%) 
Gingival bleeding  1  0/6 (0.00%)  1/6 (16.67%) 
Lip dry  1  0/6 (0.00%)  1/6 (16.67%) 
General disorders     
Pyrexia  1  5/6 (83.33%)  4/6 (66.67%) 
Oedema peripheral  1  2/6 (33.33%)  4/6 (66.67%) 
Chills  1  1/6 (16.67%)  1/6 (16.67%) 
Malaise  1  1/6 (16.67%)  1/6 (16.67%) 
Fatigue  1  1/6 (16.67%)  0/6 (0.00%) 
Oedema  1  1/6 (16.67%)  0/6 (0.00%) 
Pain  1  1/6 (16.67%)  0/6 (0.00%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  1/6 (16.67%)  0/6 (0.00%) 
Immune system disorders     
Contrast media allergy  1  1/6 (16.67%)  0/6 (0.00%) 
Hypersensitivity  1  1/6 (16.67%)  0/6 (0.00%) 
Infections and infestations     
Nasopharyngitis  1  4/6 (66.67%)  2/6 (33.33%) 
Bronchitis  1  0/6 (0.00%)  1/6 (16.67%) 
Herpes zoster  1  1/6 (16.67%)  0/6 (0.00%) 
Pneumonia bacterial  1  0/6 (0.00%)  1/6 (16.67%) 
Oral candidiasis  1  1/6 (16.67%)  0/6 (0.00%) 
Pharyngitis  1  1/6 (16.67%)  0/6 (0.00%) 
Urinary tract infection  1  1/6 (16.67%)  0/6 (0.00%) 
Injury, poisoning and procedural complications     
Thermal burn  1  0/6 (0.00%)  1/6 (16.67%) 
Investigations     
Aspartate aminotransferase increased  1  4/6 (66.67%)  4/6 (66.67%) 
Blood alkaline phosphatase increased  1  3/6 (50.00%)  2/6 (33.33%) 
Alanine aminotransferase increased  1  2/6 (33.33%)  1/6 (16.67%) 
Blood glucose increased  1  1/6 (16.67%)  1/6 (16.67%) 
Blood phosphorus decreased  1  1/6 (16.67%)  1/6 (16.67%) 
Neutrophil count decreased  1  2/6 (33.33%)  0/6 (0.00%) 
Blood albumin decreased  1  0/6 (0.00%)  1/6 (16.67%) 
Blood lactate dehydrogenase increased  1  0/6 (0.00%)  1/6 (16.67%) 
Blood pressure increased  1  0/6 (0.00%)  1/6 (16.67%) 
Ejection fraction decreased  1  0/6 (0.00%)  1/6 (16.67%) 
Electrocardiogram QT prolonged  1  1/6 (16.67%)  0/6 (0.00%) 
Eosinophil count increased  1  1/6 (16.67%)  0/6 (0.00%) 
Glucose urine present  1  0/6 (0.00%)  1/6 (16.67%) 
Haemoglobin decreased  1  1/6 (16.67%)  0/6 (0.00%) 
Platelet count decreased  1  0/6 (0.00%)  1/6 (16.67%) 
Weight increased  1  1/6 (16.67%)  0/6 (0.00%) 
White blood cell count decreased  1  1/6 (16.67%)  1/6 (16.67%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/6 (50.00%)  0/6 (0.00%) 
Hypophosphataemia  1  0/6 (0.00%)  2/6 (33.33%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/6 (16.67%)  2/6 (33.33%) 
Myalgia  1  2/6 (33.33%)  1/6 (16.67%) 
Back pain  1  1/6 (16.67%)  0/6 (0.00%) 
Muscle spasms  1  1/6 (16.67%)  0/6 (0.00%) 
Muscular weakness  1  1/6 (16.67%)  0/6 (0.00%) 
Pain in extremity  1  0/6 (0.00%)  1/6 (16.67%) 
Nervous system disorders     
Headache  1  3/6 (50.00%)  2/6 (33.33%) 
Neuropathy peripheral  1  0/6 (0.00%)  1/6 (16.67%) 
Psychiatric disorders     
Insomnia  1  1/6 (16.67%)  0/6 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  0/6 (0.00%)  1/6 (16.67%) 
Nasal inflammation  1  1/6 (16.67%)  0/6 (0.00%) 
Rhinitis allergic  1  0/6 (0.00%)  1/6 (16.67%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform  1  3/6 (50.00%)  1/6 (16.67%) 
Erythema  1  4/6 (66.67%)  1/6 (16.67%) 
Rash maculo-papular  1  4/6 (66.67%)  0/6 (0.00%) 
Alopecia  1  3/6 (50.00%)  0/6 (0.00%) 
Dermatitis bullous  1  1/6 (16.67%)  0/6 (0.00%) 
Dry skin  1  1/6 (16.67%)  0/6 (0.00%) 
Pruritus  1  1/6 (16.67%)  0/6 (0.00%) 
Rash  1  2/6 (33.33%)  0/6 (0.00%) 
Urticaria  1  1/6 (16.67%)  0/6 (0.00%) 
Paronychia  1  1/6 (16.67%)  0/6 (0.00%) 
Erythema nodosum  1  0/6 (0.00%)  1/6 (16.67%) 
Mechanical urticaria  1  0/6 (0.00%)  1/6 (16.67%) 
Skin fissures  1  0/6 (0.00%)  1/6 (16.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01928940     History of Changes
Other Study ID Numbers: 116885
First Submitted: July 3, 2013
First Posted: August 27, 2013
Results First Submitted: April 23, 2015
Results First Posted: October 2, 2015
Last Update Posted: July 24, 2017