Trial Outcomes & Findings for 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) (NCT NCT01928940)

NCT ID: NCT01928940

Last Updated: 2017-07-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 year)

Results posted on

2017-07-24

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg 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.	Phase II: GSK2118436 150 mg + GSK1120212 2 mg 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 Study STARTED	6	6
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg 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.	Phase II: GSK2118436 150 mg + GSK1120212 2 mg 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 Study Adverse Event	0	1

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.	Phase II: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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 n=12 Participants Total of all reporting groups
Age, Continuous	52.2 Years STANDARD_DEVIATION 19.83 • n=5 Participants	59.0 Years STANDARD_DEVIATION 10.99 • n=7 Participants	55.6 Years STANDARD_DEVIATION 15.70 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	6 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 year)

Population: All Treated Subject (ATS) Population: all participants who received at least one dose of study medication.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Any AEs	6 Participants
Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE) Any SAEs	1 Participants

PRIMARY outcome

Timeframe: From the start of study treatment until 21 days

Population: DLT assessment Population: all participants for whom DLT assessment was appropriately conducted

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=5 Participants 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.
Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)	0 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Inorganic Phosphorous, G4	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Uric acid, Low	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Alkaline Phosphatase, G3	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) ALT, G3	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Chloride, Low	2 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) LDH, Low	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) LDH, High	3 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Total Protein, Low	2 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Urea/BUN, Low	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Urea/BUN, High	2 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs) Uric acid, High	1 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Lymphocytes, G3	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Total Neutrophils, G3	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Basophils, High	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Eosinophils, High	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Hematocrit, Low	3 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCHC, Low	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCH, Low	2 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCV, Low	1 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Monocytes, Low	2 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Monocytes, High	3 Participants
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters RBC count, Low	4 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With the Indicated Urinalysis Parameters UOB, Baseline, Negative	6 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UOB, Baseline, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UOB, Post-Treatment, Negative	2 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UOB, Post-Treatment, Positive	1 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UGLU, Baseline, Negative	6 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UGLU, Baseline, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UGLU, Post-Treatment, Negative	3 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UGLU, Post-Treatment, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UKET, Baseline, Negative	6 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UKET, Baseline, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UKET, Post-Treatment, Negative	3 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UKET, Post-Treatment, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UP, Baseline, Negative	5 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UP, Baseline, Positive	1 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UP, Post-Treatment, Negative	2 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UP, Post-Treatment, Positive	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UUBIL, Baseline, Negative	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UUBIL, Baseline, Positive	6 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UUBIL, Post-Treatment, Negative	0 Participants
Phase I: Number of Participants With the Indicated Urinalysis Parameters UUBIL, Post-Treatment, Positive	3 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status Improved	1 Participants
Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status No change	4 Participants
Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status Deteriorated	1 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
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 SBP, Increase to Grade 2	3 Participants
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 SBP, Increase to Grade 3	0 Participants
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 DBP, Increase to Grade 2	2 Participants
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 DBP, Increase to Grade 3	1 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Change to normal or no change	3 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Decrease to <60 bpm	1 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Increase to >100 bpm	3 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Decrease to <=35 degrees C	2 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Change to normal or no change	2 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Increase to >=38 degrees C	3 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 20, n=5	0.4 Percentage of oxygen in blood Standard Deviation 1.14
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 32, n=5	0.6 Percentage of oxygen in blood Standard Deviation 1.14
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 52, n=2	-0.5 Percentage of oxygen in blood Standard Deviation 2.12
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 56, n=2	0.0 Percentage of oxygen in blood Standard Deviation 0.00
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 80, n=1	1.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Day 8, n=6	1.0 Percentage of oxygen in blood Standard Deviation 0.89
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Day 15, n=6	0.8 Percentage of oxygen in blood Standard Deviation 0.75
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 3, n=6	0.2 Percentage of oxygen in blood Standard Deviation 0.75
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 8, n=6	0.7 Percentage of oxygen in blood Standard Deviation 1.21
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 12, n=5	1.4 Percentage of oxygen in blood Standard Deviation 1.67
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 16, n=6	1.2 Percentage of oxygen in blood Standard Deviation 2.14
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 24, n=5	0.8 Percentage of oxygen in blood Standard Deviation 1.92
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 28, n=5	0.8 Percentage of oxygen in blood Standard Deviation 1.92
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 36, n=5	0.8 Percentage of oxygen in blood Standard Deviation 1.30
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 40, n=4	0.5 Percentage of oxygen in blood Standard Deviation 1.00
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 44, n=4	0.5 Percentage of oxygen in blood Standard Deviation 2.38
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 48, n=4	0.5 Percentage of oxygen in blood Standard Deviation 2.08
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 60, n=2	-0.5 Percentage of oxygen in blood Standard Deviation 0.71
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 64, n=2	0.0 Percentage of oxygen in blood Standard Deviation 0.00
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 68, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 72, n=1	1.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 76, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 84, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 88, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 92, n=1	-2.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 96, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 100, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 104, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 108, n=1	-1.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 112, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 116, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 120, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 124, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 128, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 132, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Week 136, n=1	0.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points Post-Treatment, n=4	0.8 Percentage of oxygen in blood Standard Deviation 0.96

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit ( average of 1.38 year)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 3, n=6	-4.87 Kilogram (Kg) Standard Deviation 6.046
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 8, n=6	-4.43 Kilogram (Kg) Standard Deviation 6.274
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 12, n=6	-4.13 Kilogram (Kg) Standard Deviation 6.436
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 16, n=6	-4.00 Kilogram (Kg) Standard Deviation 6.801
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 20, n=5	-0.62 Kilogram (Kg) Standard Deviation 2.295
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 24, n=5	-0.70 Kilogram (Kg) Standard Deviation 1.402
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 28, n=5	-0.36 Kilogram (Kg) Standard Deviation 1.850
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 32, n=5	-0.38 Kilogram (Kg) Standard Deviation 1.809
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 36, n=5	-0.78 Kilogram (Kg) Standard Deviation 1.821
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 40, n=4	-1.43 Kilogram (Kg) Standard Deviation 1.305
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 44, n=4	-0.68 Kilogram (Kg) Standard Deviation 1.759
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 48, n=4	-1.03 Kilogram (Kg) Standard Deviation 2.081
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 52, n=2	0.15 Kilogram (Kg) Standard Deviation 2.475
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 56, n=2	-0.30 Kilogram (Kg) Standard Deviation 1.556
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 60, n=2	-0.35 Kilogram (Kg) Standard Deviation 2.475
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 64, n=2	-0.05 Kilogram (Kg) Standard Deviation 2.475
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 68, n=1	-2.60 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 72, n=1	-2.10 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 76, n=1	-1.20 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 80, n=1	-0.70 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 84, n=1	-0.70 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 88, n=1	-1.20 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 92, n=1	-0.80 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 96, n=1	-0.80 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 100, n=1	-0.80 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 104, n=1	-0.50 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 108, n=1	-1.00 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 112, n=1	-1.00 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 116, n=1	-0.50 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 120, n=1	-0.60 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 124, n=1	-0.70 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 128, n=1	-0.60 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 132, n=1	-0.80 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Week 136, n=1	-0.50 Kilogram (Kg) Standard Deviation NA There were too few participants to provide a dispersion value.
Phase I: Change From Baseline in Weight at the Indicated Time Points Post-Treatment, n=4	-0.05 Kilogram (Kg) Standard Deviation 1.457

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 year)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 12, Abnormal-CS, n=6	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 24, Normal, n=5	4 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 48, Abnormal-NCS, n=4	2 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 132, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Baseline, Normal, n=6	4 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Baseline, Abnormal-NCS, n=6	2 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Baseline, Abnormal-CS, n=6	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 3, Normal, n=6	5 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 3, Abnormal-NCS, n=6	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 3, Abnormal-CS, n=6	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 12, Normal, n=6	5 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 12, Abnormal-NCS, n=6	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 24, Abnormal-NCS, n=5	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 24, Abnormal-CS, n=5	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 36, Normal, n=5	4 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 36, Abnormal-NCS, n=5	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 36, Abnormal-CS, n=5	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 48, Normal, n=4	2 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 48, Abnormal-CS, n=4	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 60, Normal, n=2	2 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 60, Abnormal-NCS, n=2	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 60, Abnormal-CS, n=2	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 72, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 72, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 72, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 84, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 84, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 84, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 96, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 96, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 96, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 108, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 108, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 108, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 120, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 120, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 120, Abnormal-CS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 132, Normal, n=1	1 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Week 132, Abnormal-NCS, n=1	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Post-Treatment, Normal, n=3	3 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Post-Treatment, Abnormal-NCS, n=3	0 Participants
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points Post-Treatment, Abnormal-CS, n=3	0 Participants

PRIMARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) Any Increase	0 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) No change	0 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) 0-<10 Decrease	5 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) 10-19 Decrease	1 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) >=20 Decrease	0 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) >=10 Decrease and >=LLN	1 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) >=10 Decrease and below LLN	0 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) >=20 Decrease and >=LLN	0 Participants
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO) >=20 Decrease and below LLN	0 Participants

PRIMARY outcome

Timeframe: Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)

Population: ATS Population

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).

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participant With Confirmed Overall Response Investigator-Assessed	5 Participants
Phase II: Number of Participant With Confirmed Overall Response BICR-Assessed	5 Participants

SECONDARY outcome

Timeframe: 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)

Population: 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).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2118436, AUC[0-t], Day 1, n=6	12850.5346 hr*nanogram (ng)/mL Geometric Coefficient of Variation 37.3
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2118436, AUC[0-t], Day 21, n=6	10075.3530 hr*nanogram (ng)/mL Geometric Coefficient of Variation 32.4
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2118436, AUC[0-12], Day 1, n=6	11414.9211 hr*nanogram (ng)/mL Geometric Coefficient of Variation 41.3
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2118436, AUC[0-12], Day 21, n=6	10138.0887 hr*nanogram (ng)/mL Geometric Coefficient of Variation 33.1
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2118436, AUC[0-inf], Day 1, n=6	13485.6357 hr*nanogram (ng)/mL Geometric Coefficient of Variation 36.9
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2285403, AUC[0-t], Day 1, n=6	10530.0297 hr*nanogram (ng)/mL Geometric Coefficient of Variation 39.4
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2285403, AUC[0-t], Day 21, n=6	7199.9862 hr*nanogram (ng)/mL Geometric Coefficient of Variation 29.9
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2285403, AUC[0-12], Day 1, n=6	7929.4506 hr*nanogram (ng)/mL Geometric Coefficient of Variation 64.3
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2285403, AUC[0-12], Day 21, n=6	7273.0445 hr*nanogram (ng)/mL Geometric Coefficient of Variation 30.6
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2285403, AUC[0-inf], Day 1, n=6	13903.4979 hr*nanogram (ng)/mL Geometric Coefficient of Variation 67.9
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2298683, AUC[0-t], day 1, n=6	50834.2106 hr*nanogram (ng)/mL Geometric Coefficient of Variation 106.0
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2298683, AUC[0-t], Day 21, n=6	108578.495 hr*nanogram (ng)/mL Geometric Coefficient of Variation 36.1
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2298683, AUC[0-12], Day 1, n=6	18963.4767 hr*nanogram (ng)/mL Geometric Coefficient of Variation 255.7
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2298683, AUC[0-12], Day 21, n=6	113205.044 hr*nanogram (ng)/mL Geometric Coefficient of Variation 36.8
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2298683, AUC[0-inf], Day 1, n=5	125748.810 hr*nanogram (ng)/mL Geometric Coefficient of Variation 41.8
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2167542, AUC[0-t], Day 1, n=6	571.5619 hr*nanogram (ng)/mL Geometric Coefficient of Variation 170.4
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2167542, AUC[0-t], Day 21, n=6	2503.0667 hr*nanogram (ng)/mL Geometric Coefficient of Variation 92.7
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2167542, AUC[0-12], Day 1, n=6	116.1860 hr*nanogram (ng)/mL Geometric Coefficient of Variation 269.6
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2167542, AUC[0-12], Day 21, n=4	2755.2522 hr*nanogram (ng)/mL Geometric Coefficient of Variation 122.0
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK2167542, AUC[0-inf], Day 1, n=1	4628.4351 hr*nanogram (ng)/mL Geometric Coefficient of Variation NA There were too few participants to provide a dispersion value
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK1120212, AUC[0-t], Day 1, n=6	69.3090 hr*nanogram (ng)/mL Geometric Coefficient of Variation 50.2
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK1120212, AUC[0-t], Day 21, n=6	261.2787 hr*nanogram (ng)/mL Geometric Coefficient of Variation 20.9
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK1120212, AUC[0-24], Day 1, n=5	82.5215 hr*nanogram (ng)/mL Geometric Coefficient of Variation 23.1
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK1120212, AUC[0-24], Day 21, n=6	447.9452 hr*nanogram (ng)/mL Geometric Coefficient of Variation 25.5
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose GSK1120212, AUC[0-inf], Day 1, n=5	375.5275 hr*nanogram (ng)/mL Geometric Coefficient of Variation 23.1

SECONDARY outcome

Population: PK Population

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Day 1	2497.383 ng/mL Geometric Coefficient of Variation 69.7
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Day 21	3431.280 ng/mL Geometric Coefficient of Variation 12.0
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Day 1	1336.296 ng/mL Geometric Coefficient of Variation 70.1
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Day 21	1995.847 ng/mL Geometric Coefficient of Variation 14.8
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Day 1	3689.039 ng/mL Geometric Coefficient of Variation 75.5
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Day 21	12303.403 ng/mL Geometric Coefficient of Variation 32.5
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Day 1	50.405 ng/mL Geometric Coefficient of Variation 149.7
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Day 21	323.863 ng/mL Geometric Coefficient of Variation 82.4
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Day 1	7.824 ng/mL Geometric Coefficient of Variation 112.1
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Day 21	32.522 ng/mL Geometric Coefficient of Variation 20.2

SECONDARY outcome

Timeframe: At pre-dose on Day 8, Day 15, Weeks 3, 8, 16 and 24

Population: PK Population.Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Week 24, n=5	13.72 ng/mL Geometric Coefficient of Variation 41.3
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Day 8, n=6	149.61 ng/mL Geometric Coefficient of Variation 111.9
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Day 15, n=6	106.09 ng/mL Geometric Coefficient of Variation 72.8
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Week 3, n=6	93.87 ng/mL Geometric Coefficient of Variation 82.0
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Week 8, n=6	89.12 ng/mL Geometric Coefficient of Variation 239.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Week 16, n=6	100.10 ng/mL Geometric Coefficient of Variation 121.8
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2285403, Week 24, n=5	117.93 ng/mL Geometric Coefficient of Variation 121.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Day 8, n=6	118.36 ng/mL Geometric Coefficient of Variation 188.3
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Day 15, n=6	84.25 ng/mL Geometric Coefficient of Variation 136.2
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Week 3, n=6	78.14 ng/mL Geometric Coefficient of Variation 149.3
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Week 8, n=6	78.29 ng/mL Geometric Coefficient of Variation 591.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Week 16, n=6	105.05 ng/mL Geometric Coefficient of Variation 206.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2118436, Week 24, n=5	121.85 ng/mL Geometric Coefficient of Variation 183.9
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Day 8, n=6	6011.00 ng/mL Geometric Coefficient of Variation 39.8
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Day 15, n=6	5141.38 ng/mL Geometric Coefficient of Variation 39.5
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Week 3, n=6	6210.90 ng/mL Geometric Coefficient of Variation 51.8
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Week 8, n=6	4408.24 ng/mL Geometric Coefficient of Variation 65.0
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Week 16, n=6	4022.93 ng/mL Geometric Coefficient of Variation 39.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2298683, Week 24, n=5	4294.86 ng/mL Geometric Coefficient of Variation 51.9
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Day 8, n=6	217.73 ng/mL Geometric Coefficient of Variation 46.7
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Day 15, n=6	161.11 ng/mL Geometric Coefficient of Variation 107.5
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Week 3, n=6	224.32 ng/mL Geometric Coefficient of Variation 83.6
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Week 8, n=6	220.93 ng/mL Geometric Coefficient of Variation 52.2
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Week 16, n=6	270.15 ng/mL Geometric Coefficient of Variation 107.5
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK2167542, Week 24, n=5	227.75 ng/mL Geometric Coefficient of Variation 101.5
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Day 8, n=6	11.36 ng/mL Geometric Coefficient of Variation 43.0
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Day 15, n=6	12.47 ng/mL Geometric Coefficient of Variation 22.4
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Week 3, n=6	13.80 ng/mL Geometric Coefficient of Variation 25.6
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Week 8, n=6	14.52 ng/mL Geometric Coefficient of Variation 65.0
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose GSK1120212, Week 16, n=6	13.47 ng/mL Geometric Coefficient of Variation 39.4

SECONDARY outcome

Population: PK Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles)

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
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 GSK2118436, t1/2, Day 1, n=6	4.5398 hr Interval 2.776 to 9.645
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 GSK2118436, tmax, Day 1, n=6	2.425 hr Interval 1.43 to 3.85
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 GSK2118436, tmax, Day 21, n=6	1.685 hr Interval 0.97 to 1.97
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 GSK2285403, t1/2, Day 1, n=6	4.2086 hr Interval 3.574 to 55.294
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 GSK2285403, tmax, Day 1, n=6	3.410 hr Interval 2.93 to 11.93
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 GSK2285403, tmax, Day 21, n=6	1.950 hr Interval 1.47 to 2.93
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 GSK2298683, t1/2, Day 1, n=5	15.5414 hr Interval 11.652 to 21.159
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 GSK2298683, tmax, Day 1, n=6	9.840 hr Interval 7.92 to 23.82
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 GSK2298683, tmax, Day 21, n=6	4.955 hr Interval 2.75 to 5.98
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 GSK2167542, t1/2, Day 1, n=1	55.8643 hr Interval 55.8643 to 55.8643
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 GSK2167542, tmax, Day 1, n=6	23.885 hr Interval 11.65 to 24.28
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 GSK2167542, tmax, Day 21, n=6	4.505 hr Interval 1.97 to 9.92
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 GSK1120212, t1/2, Day 1, n=5	89.5954 hr Interval 39.029 to 126.331
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 GSK1120212, tmax, Day 1, n=6	0.965 hr Interval 0.92 to 23.82
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 GSK1120212, tmax, Day 21, n=6	1.210 hr Interval 0.92 to 5.93

SECONDARY outcome

Timeframe: Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Confirmed Overall Response Rate Investigator-Assessed	5 Participants
Phase I: Number of Participants With Confirmed Overall Response Rate BICR-Assessed	3 Participants

SECONDARY outcome

Timeframe: Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Number of Participants With Unconfirmed Overall Response Rate Investigator-Assessed	5 Participants
Phase I: Number of Participants With Unconfirmed Overall Response Rate BICR-Assessed	3 Participants

SECONDARY outcome

Timeframe: From start of the treatment until disease progression or death (average of 1.38 years)

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Progression Free Survival (PFS) Investigator-Assessed, n=6	NA Weeks Interval 16.0 to 65.1 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.
Phase I: Progression Free Survival (PFS) BICR-Assessed, n=6	NA Weeks Interval 9.0 to 65.1 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.

SECONDARY outcome

Timeframe: From start of the treatment until disease progression or death (average of 1.38 years)

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase I: Duration of Response Investigator-Assessed, n=5	NA Weeks Interval 17.4 to 57.1 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.
Phase I: Duration of Response BICR-Assessed, n=3	NA Weeks Interval 32.1 to 57.1 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.

SECONDARY outcome

Timeframe: Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)

Population: ATS Population

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With Unconfirmed Overall Response Investigator-Assessed	5 Participants
Phase II: Number of Participants With Unconfirmed Overall Response BICR-Assessed	5 Participants

SECONDARY outcome

Timeframe: From start of the treatment until disease progression or death (average of 1.38 years)

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Progression Free Survival (PFS) Investigator-Assessed, n=6	NA Weeks Interval 19.0 to 128.4 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.
Phase II: Progression Free Survival (PFS) BICR-Assessed, n=6	NA Weeks Interval 19.0 to 128.4 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.

SECONDARY outcome

Timeframe: From start of the treatment until disease progression or death (average of 1.38 years)

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Duration of Response Investigator-Assessed, n=5	NA Weeks Interval 16.0 to 120.1 There were too few participants to provide a median PFS
Phase II: Duration of Response BICR-Assessed, n=5	NA Weeks Interval 11.1 to 120.1 There were too few participants to provide a median PFS

SECONDARY outcome

Timeframe: From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event Any AE	6 Participants
Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event Any SAE	0 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters Inorganic Phosphorous, G3	2 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters Chloride, High	2 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters LDH, High	5 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters Total Protein, Low	2 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters Urea/BUN, High	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters Uric acid, Low	1 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Total Neutrophils, G3	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Eosinophils, High	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Hematocrit, Low	2 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCHC, Low	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCH, Low	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCV, Low	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters MCV, High	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Monocytes, Low	3 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters Monocytes, High	4 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters RBC count, Low	1 Participants
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters RBC count, High	1 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With the Indicated Urinalysis Results UOB, Baseline, Negative	6 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UOB, Baseline, Positive	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UOB, Post-Treatment, Negative	3 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UOB, Post-Treatment, Positive	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UGLU, Baseline, Negative	6 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UGLU, Baseline, Positive	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UGLU, Post-Treatment, Negative	2 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UGLU, Post-Treatment, Positive	1 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UKET, Baseline, Negative	5 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UKET, Baseline, Positive	1 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UKET, Post-Treatment, Negative	2 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UKET, Post-Treatment, Positive	1 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UP, Baseline, Negative	6 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UP, Baseline, Positive	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UP, Post-Treatment, Negative	2 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UP, Post-Treatment, Positive	1 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UUBIL, Baseline, Negative	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UUBIL, Baseline, Positive	6 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UUBIL, Post-Treatment, Negative	0 Participants
Phase II: Number of Participants With the Indicated Urinalysis Results UUBIL, Post-Treatment, Positive	3 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status Improved	0 Participants
Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status No change	4 Participants
Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status Deteriorated	2 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
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 SBP, Increase to Grade 2	3 Participants
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 SBP, Increase to Grade 3	0 Participants
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 DBP, Increase to Grade 2	5 Participants
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 DBP, Increase to Grade 3	0 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Decrease to <60 bpm	1 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Change to normal or no change	4 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate Increase to >100 bpm	1 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Decrease to <=35 degrees C	2 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Change to normal or no change	4 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature Increase to >=38 degrees C	0 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Day 8, n=6	-0.2 Percentage of oxygen in blood Standard Deviation 0.98
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Day 15, n=6	0.3 Percentage of oxygen in blood Standard Deviation 1.51
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 3, n=6	0.5 Percentage of oxygen in blood Standard Deviation 0.84
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 8, n=6	0.5 Percentage of oxygen in blood Standard Deviation 1.05
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 12, n=6	-0.2 Percentage of oxygen in blood Standard Deviation 0.98
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 16, n=6	0.3 Percentage of oxygen in blood Standard Deviation 1.51
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 20, n=5	-1.0 Percentage of oxygen in blood Standard Deviation 1.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 24, n=5	0.2 Percentage of oxygen in blood Standard Deviation 1.64
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 28, n=5	-0.2 Percentage of oxygen in blood Standard Deviation 0.84
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 32, n=5	-0.6 Percentage of oxygen in blood Standard Deviation 1.14
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 36, n=5	-0.4 Percentage of oxygen in blood Standard Deviation 1.34
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 40, n=5	0.0 Percentage of oxygen in blood Standard Deviation 1.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 44, n=4	-1.3 Percentage of oxygen in blood Standard Deviation 2.22
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 48, n=4	1.0 Percentage of oxygen in blood Standard Deviation 1.41
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 52, n=3	1.0 Percentage of oxygen in blood Standard Deviation 1.73
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 56, n=3	-0.7 Percentage of oxygen in blood Standard Deviation 0.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 60, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 1.15
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 64, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 0.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 68, n=3	0.0 Percentage of oxygen in blood Standard Deviation 1.00
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 72, n=3	-0.7 Percentage of oxygen in blood Standard Deviation 1.53
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 76, n=3	-1.0 Percentage of oxygen in blood Standard Deviation 0.00
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 80, n=3	0.0 Percentage of oxygen in blood Standard Deviation 1.00
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 84, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 1.53
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 88, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 1.53
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 92, n=3	0.3 Percentage of oxygen in blood Standard Deviation 0.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 96, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 0.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 100, n=3	-0.7 Percentage of oxygen in blood Standard Deviation 1.15
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 104, n=3	-0.3 Percentage of oxygen in blood Standard Deviation 1.53
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 108, n=3	0.0 Percentage of oxygen in blood Standard Deviation 1.00
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 112, n=3	0.0 Percentage of oxygen in blood Standard Deviation 1.00
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 116, n=3	-0.7 Percentage of oxygen in blood Standard Deviation 0.58
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 120, n=2	-0.5 Percentage of oxygen in blood Standard Deviation 0.71
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 124, n=1	-2.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 128, n=1	1.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Week 132, n=1	-2.0 Percentage of oxygen in blood Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points Post-Treatment, n=3	1.3 Percentage of oxygen in blood Standard Deviation 0.58

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 3, n=6	-0.68 Kg Standard Deviation 0.538
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 8, n=6	-0.22 Kg Standard Deviation 0.553
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 12, n=6	-0.30 Kg Standard Deviation 1.273
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 16, n=6	0.05 Kg Standard Deviation 1.947
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 20, n=5	-0.32 Kg Standard Deviation 2.318
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 24, n=5	0.06 Kg Standard Deviation 2.243
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 28, n=5	0.18 Kg Standard Deviation 2.500
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 32, n=5	0.42 Kg Standard Deviation 2.607
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 36, n=5	0.98 Kg Standard Deviation 3.016
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 40, n=5	0.62 Kg Standard Deviation 2.734
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 44, n=4	0.80 Kg Standard Deviation 3.790
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 48, n=4	0.68 Kg Standard Deviation 3.527
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 52, n=3	1.27 Kg Standard Deviation 3.993
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 56, n=3	2.23 Kg Standard Deviation 3.932
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 60, n=3	2.83 Kg Standard Deviation 3.879
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 64, n=3	2.70 Kg Standard Deviation 4.246
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 68, n=3	2.87 Kg Standard Deviation 4.143
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 72, n=3	2.87 Kg Standard Deviation 4.165
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 76, n=3	3.63 Kg Standard Deviation 2.793
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 80, n=3	3.43 Kg Standard Deviation 4.007
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 84, n=3	4.37 Kg Standard Deviation 4.008
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 88, n=3	3.80 Kg Standard Deviation 3.905
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 92, n=3	4.13 Kg Standard Deviation 3.496
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 96, n=3	4.13 Kg Standard Deviation 3.630
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 100, n=3	3.53 Kg Standard Deviation 3.219
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 104, n=3	4.00 Kg Standard Deviation 4.557
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 108, n=3	3.93 Kg Standard Deviation 4.800
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 112, n=3	3.60 Kg Standard Deviation 4.649
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 116, n=3	4.20 Kg Standard Deviation 4.859
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 120, n=2	5.95 Kg Standard Deviation 2.192
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 124, n=1	7.50 Kg Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 128, n=1	5.80 Kg Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Weight at the Indicated Time Points Week 132, n=1	5.30 Kg Standard Deviation NA There were too few participants to provide a dispersion value.
Phase II: Change From Baseline in Weight at the Indicated Time Points Post-Treatment, n=3	0.13 Kg Standard Deviation 2.155

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles).

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Post-Treatment, Normal, n=3	3 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Baseline, Normal, n=6	5 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Baseline, Abnormal-NCS, n=6	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Baseline, Abnormal-CS, n=6	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 3, Normal, n=6	4 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 3, Abnormal-NCS, n=6	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 3, Abnormal-CS, n=6	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 12, Normal, n=6	4 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 12, Abnormal-NCS, n=6	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 12, Abnormal-CS, n=6	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 24, Normal, n=5	3 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 24, Abnormal-NCS, n=5	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 24, Abnormal-CS, n=5	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 36, Normal, n=5	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 36, Abnormal-NCS, n=5	3 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 36, Abnormal-CS, n=5	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 48, Normal, n=4	3 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 48, Abnormal-NCS, n=4	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 48, Abnormal-CS, n=4	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 60, Normal, n=3	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 60, Abnormal-NCS, n=3	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 60, Abnormal-CS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 72, Normal, n=3	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 72, Abnormal-NCS, n=3	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 72, Abnormal-CS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 84, Normal, n=3	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 84, Abnormal-NCS, n=3	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 84, Abnormal-CS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 96, Normal, n=3	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 96, Abnormal-NCS, n=3	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 96, Abnormal-CS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 108, Normal, n=3	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 108, Abnormal-NCS, n=3	2 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 108, Abnormal-CS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 120, Normal, n=2	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 120, Abnormal-NCS, n=2	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 120, Abnormal-CS, n=2	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 132, Normal, n=1	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 132, Abnormal-NCS, n=1	1 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Week 132, Abnormal-CS, n=1	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Post-Treatment, Abnormal-NCS, n=3	0 Participants
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points Post-Treatment, Abnormal-CS, n=3	0 Participants

SECONDARY outcome

Timeframe: From Baseline until the post-treatment Visit (average of 1.38 years)

Population: ATS Population

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.

Outcome measures

Outcome measures
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 Participants 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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram Any Increase	1 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram No change	0 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram 0-<10 Decrease	3 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram 10-19 Decrease	2 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram >=20 Decrease	0 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram >=10 Decrease and >=LLN	2 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram >=10 Decrease and below LLN	0 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram >=20 Decrease and >=LLN	0 Participants
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram >=20 Decrease and below LLN	0 Participants

Adverse Events

Phase I: GSK2118436 150 mg + GSK1120212 2 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II: GSK2118436 150 mg + GSK1120212 2 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase I: GSK2118436 150 mg + GSK1120212 2 mg n=6 participants at risk 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.	Phase II: GSK2118436 150 mg + GSK1120212 2 mg n=6 participants at risk 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.
Respiratory, thoracic and mediastinal disorders Pneumonitis	16.7% 1/6 • 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). 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.	0.00% 0/6 • 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). 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.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER