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)

A Japanese Open-label Phase I/II Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of GSK2118436 and GSK1120212 Combination Therapy in Subjects With BRAF V600E/K Mutation Positive Advanced Solid Tumors (Phase I Part) and BRAF V600E/K Mutation Positive Cutaneous Melanoma (Phase II Part).

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01928940

Enrollment

Registered

2013-08-27

Start date

2013-08-15

Completion date

2016-07-04

Last updated

2017-07-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Tumours

Keywords

Advanced solid tumors, BRAF, Melanoma

Brief summary

Detailed description

This is a Japanese Phase I/II, open-label, non-controlled study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of the combination of GSK2118436 and GSK1120212 in subjects with BRAF V600E/K mutation positive advanced solid tumors (Phase I part) and BRAF V600E/K mutation positive cutaneous melanoma (Phase II part). Phase I part is designed to primarily assess the safety and tolerability of GSK2118436 and GSK1120212 combination therapy in subjects with BRAF V600E/K mutation positive advanced solid tumors. Six evaluable subjects will be enrolled into Phase I part and receive the combination therapy of GSK2118436 (150 mg, twice daily) and GSK1120212 (2 mg, once daily). A decision for starting Phase II part will be made by careful review based on available safety, tolerability and pharmacokinetic data in Phase I part. Phase II part is designed to primarily evaluate ORR of the combination as first-line therapy in subjects with unresectable (Stage IIIC) or metastatic (Stage IV) BRAF V600E/K mutation positive cutaneous melanoma. Subjects who have had prior systemic anti-cancer treatment in the advanced or metastatic setting will not be eligible for Phase II part although prior systemic treatment in the adjuvant setting will be allowed. Six evaluable subjects will be enrolled in Phase II part.

Interventions

DRUGdabrafenib

150 mg twice daily

DRUGtrametinib

2 mg once daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Capable of given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Male or female age 20 years or greater; able to swallow and retain oral medication. * BRAF mutation positive advanced solid tumor ( Phase I part). BRAF mutation positive melanoma (Phase II part). * Measurable disease according to RECIST version 1.1. * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Agree to contraception requirements. * Adequate organ system function.

Exclusion criteria

* Currently receiving cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy). * Phase II part ONLY: Prior systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) for Stage IIIC (unresectable) or Stage IV (metastatic) melanoma. Prior systemic treatment in the adjuvant setting is allowed. * Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 28 days prior to the study treatment (6 weeks for prior nitrosourea or mitomycin C), or daily or weekly chemotherapy without the potential for delayed toxicity within 14 days prior to the study treatment. Limited radiotherapy within the last 2 weeks. (Note: Ipilimumab treatment must end at least 8 weeks prior to the study treatment.) * Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to the study treatment. * Current use of a prohibited medication or requires any of these medications during treatment with the study drugs. * A history of another malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. * Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures (e.g., uncontrolled diabetes). * Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of drugs. * History of pneumonitis or interstitial lung disease. * Known HIV infection. * Certain cardiac abnormality * A history or current evidence/risk of retinal vein occlusion or central serous retinopathy. * Pregnant or lactating female.

Design outcomes

Primary

Measure	Time frame	Description
Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)	From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 year)	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.
Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)	From the start of study treatment until 21 days	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.
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs)	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With the Indicated Urinalysis Parameters	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
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	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Change From Baseline in Weight at the Indicated Time Points	From Baseline until the post-treatment Visit ( average of 1.38 year)	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.
Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points	From Baseline until the post-treatment Visit (average of 1.38 year)	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.
Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO)	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participant With Confirmed Overall Response	Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)	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).

Secondary

Measure	Time frame	Description
Phase II: Number of Participants With the Indicated Urinalysis Results	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
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	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose	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)	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.
Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Change From Baseline in Weight at the Indicated Time Points	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose	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)	Blood samples were collected from each participant at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr post-dose on Day 21 (repeat dose) for PK analysis. GSK2118436 metabolites included GSK2285403, GSK2298683 and GSK2167542. Cmax was determined from the raw concentration-time data.
Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose	At pre-dose on Day 8, Day 15, Weeks 3, 8, 16 and 24	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.
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	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)	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.
Phase I: Number of Participants With Confirmed Overall Response Rate	Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)	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.
Phase I: Number of Participants With Unconfirmed Overall Response Rate	Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)	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.
Phase I: Progression Free Survival (PFS)	From start of the treatment until disease progression or death (average of 1.38 years)	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.
Phase I: Duration of Response	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.
Phase II: Number of Participants With Unconfirmed Overall Response	Every 8 weeks from start of the treatment until disease progression, death, or withdrawal of consent (average of 1.38 years)	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.
Phase II: Progression Free Survival (PFS)	From start of the treatment until disease progression or death (average of 1.38 years)	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.
Phase II: Duration of Response	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.
Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event	From the start of study treatment until 30 days after study treatment discontinuation (average of 1.38 years)	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.
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters	From Baseline until the post-treatment Visit (average of 1.38 years)	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.
Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	From Baseline until the post-treatment Visit (average of 1.38 years)	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.

Countries

Japan

Participant flow

Pre-assignment details

This study consisted of 2 parts: Phase I part included Japanese participants (par.) with BRAF V600E/K mutation-positive advanced solid tumors and the Phase II part included Japanese par. with BRAF V600E/K mutation-positive cutaneous melanoma.

Participants by arm

Arm	Count
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.	6
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.	6
Total	12

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1

Baseline characteristics

Characteristic	Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: GSK2118436 150 mg + GSK1120212 2 mg	Total
Age, Continuous	52.2 Years STANDARD_DEVIATION 19.83	59.0 Years STANDARD_DEVIATION 10.99	55.6 Years STANDARD_DEVIATION 15.7
Race/Ethnicity, Customized Asian - Japanese Heritage	6 Participants	6 Participants	12 Participants
Sex: Female, Male Female	5 Participants	2 Participants	7 Participants
Sex: Female, Male Male	1 Participants	4 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	6 / 6	6 / 6
serious Total, serious adverse events	1 / 6	0 / 6

Outcome results

Primary

Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen,that is called as blood oxygen saturation or SpO2. Change from Baseline was calculated as the individual post-Baseline value (Days 8,15; Weeks 3 to 136 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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 1.3
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Change From Baseline in Weight at the Indicated Time Points

Mean change in body weight from Baseline was determined. Change from Baseline was calculated as the individual post-Baseline value (Weeks 3 to 136 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 28, n=5	-0.36 Kilogram (Kg)	Standard Deviation 1.85
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 68, n=1	-2.60 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 72, n=1	-2.10 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 76, n=1	-1.20 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 80, n=1	-0.70 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 84, n=1	-0.70 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 88, n=1	-1.20 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 92, n=1	-0.80 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 96, n=1	-0.80 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 100, n=1	-0.80 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 104, n=1	-0.50 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 108, n=1	-1.00 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 112, n=1	-1.00 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 116, n=1	-0.50 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 120, n=1	-0.60 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 124, n=1	-0.70 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 128, n=1	-0.60 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 132, n=1	-0.80 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Change From Baseline in Weight at the Indicated Time Points	Week 136, n=1	-0.50 Kilogram (Kg)	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase II: Number of Participant With Confirmed Overall Response

Confirmed overall response (ORR) is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve (respond), stay the same (stabilize), or worsen (progress) during treatment. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). ORR was assessed by investigator and blinded independent central review (BICR).

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participant With Confirmed Overall Response	Investigator-Assessed	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participant With Confirmed Overall Response	BICR-Assessed	5 Participants

p-value: <0.000195% CI: [35.9, 99.6]Exact binomial test

Primary

Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)

A DLT was defined as an event occurred during the first 21 days after the first dose of study drugs and met any of the following criteria, according to National Cancer Institutes (NCI) common terminology criteria for AE (CTCAE) grade (G) version 4.0: G4 hematological toxicity; G3 or G4 non-hematologic toxicity (including rash, nausea, vomiting and diarrhea only if uncontrolled with supportive therapy); rash \>=G3 that required dose reduction despite supportive care; a G2 or greater non-hematological toxicity that in the judgment of the investigator and medical monitor; dose interruption of greater than 14 consecutive days due to unresolved toxicity; any new G2 or greater valvular heart disease and significant alteration in cardiac valve morphology from Baseline.

Time frame: From the start of study treatment until 21 days

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

Arm	Measure	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)	0 Participants

Primary

Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)

An AE is defined as any untoward medical occurrence (MO) in a part. temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. SAE is defined as any untoward MO that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect and protocol-specific SAEs:ALT\>=3xupper limit of normal(ULN) and bilirubin\>=2xULN(\>35% direct) (or ALT\>=3xULN, international normalized ratio\>1.5), any new primary cancers, treatment emergent malignancies except basal cell carcinoma, symptomatic or asymptomatic LVEF decrease, retinal pigment epithelial detachment or retinal vein occlusion, pyrexia with hypotension,or dehydration or renal insufficiency,or severe (\>=G3) rigor/chills.

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

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

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)	Any AEs	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)	Any SAEs	1 Participants

Primary

Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points

Single twelve (12)-lead ECGs were perfomred at Baseline, Weeks 3 to 132 and post-treatment Visit. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator.

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

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

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points	Baseline, Normal, n=6	4 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Number of Participants With the Indicated Urinalysis Parameters

Urine samples were collected for urine dipstick analysis at Baseline and at the post-treatment Visit. The number of participants with negative (absence) and positive (presence: trace, 1+, 2+, 3+, 4+ or 5+) results for urine occult blood (UOB), urine glucose (UGLU), urine ketones (UKET), urine protein (UP) and urine urobilinogen (UUBIL) were summarized. The Baseline value is defined as the last pre-treatment value observed.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UUBIL, Post-Treatment, Positive	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UP, Post-Treatment, Negative	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UOB, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UOB, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UOB, Post-Treatment, Negative	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UOB, Post-Treatment, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UGLU, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UGLU, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UGLU, Post-Treatment, Negative	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UGLU, Post-Treatment, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UKET, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UKET, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UKET, Post-Treatment, Negative	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UKET, Post-Treatment, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UP, Baseline, Negative	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UP, Baseline, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UP, Post-Treatment, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UUBIL, Baseline, Negative	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UUBIL, Baseline, Positive	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Urinalysis Parameters	UUBIL, Post-Treatment, Negative	0 Participants

Primary

Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs)

CCPs were graded according to NCI CTCAE grade version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters (para) for which an increase to G3 or G4 from BL G occurred. CCPs that were not G according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those para for which the category decreased to Low or increased to High relative to the BL category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. CCPs included: albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, calcium, creatinine, glucose, potassium, magnesium, sodium, inorganic phosphorus, chloride, lactate dehydrogenase (LDH), total protein, urea/blood urea nitrogen (BUN) and uric acid.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters

Hematology parameters were summarized according to NCI CTCAE G, version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline G occurred. For hematology parameters that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Hematology parameters included: hemoglobin, lymphocytes, total neutrophils, platelet count, white blood cell (WBC) counts, basophils, eosinophils, hematocrit, mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes and red blood cell (RBC) count.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Lymphocytes, G3	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Basophils, High	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Eosinophils, High	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Hematocrit, Low	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCHC, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCH, Low	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCV, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Monocytes, Low	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Monocytes, High	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	RBC count, Low	4 Participants

Primary

Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status

The ECOG pef status 5-point scale is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the par. and to determine appropriate treatment and prognosis: G0, fully active, able to carry on all pre-disease pef without restriction. G1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, example, light house work, office work. G2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about \>50 percent (%) of waking hrs. G3, capable of only limited selfcare; confined to bed or chair \>50% of waking hrs. G4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. G5, dead. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Number of par. who improved, had no change, or deteriorated in pef status from BL is summarized.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate

Change from Baseline in heart rate is categorized as decrease to \<60 beats per minute (bpm), change to normal or no change, and increase to \>100 bpm relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant's heart rate value decreased to \<60 bpm and increased to \>100 bpm post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	Decrease to <60 bpm	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	Increase to >100 bpm	3 Participants

Primary

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO)

Absolute change from Baseline in LVEF were summarized at each scheduled assessment time and in the worst-case post Baseline. Only the post Baseline assessments that used the same method (ECHO or Multi Gated Acquisition Scan \[MUGA\]) as the Baseline assessments were used to derive the change from Baseline. The change from Baseline was categorized as: any increase; no change; 0-\<10 Decrease, 10-19 Decrease, \>=20 Decrease, \>=10 Decrease and \>= lower limit of normal (LLN), \>=10 Decrease and below LLN, \>=20 Decrease and \>=LLN and \>=20 Decrease and below LLN. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature

Change from Baseline in temperature is categorized as a decrease to \<=35 degrees celsius (C), change to normal or no change as 35-38 degrees C, and increase to \>=38 degrees C relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant temperature value decreased to \<=35 degrees C and increased to \>=38 degrees C post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	Decrease to <=35 degrees C	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	Increase to >=38 degrees C	3 Participants

Primary

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

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were graded using (NCI CTCAE version 4.0). SBP was categorized as: G1 (Increase to \>=120 to 140 millimeters of mercury \[mmHg\]), G2 (Increase to \>=140 to \<160 mmHg), and G3 (Increase to \>=160 mmHg). DBP was categorized as: G1 (Increase to \>=80 to \<90 mmHg), G2 (Increase to \>=90 to \<100 mmHg), and G3 (Increase to \>=100 mmHg). The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of G0.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Secondary

Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose

Blood samples were collected from each par. at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr post-dose on Day 21 (repeat dose) for PK analysis. GSK2118436 metabolites included GSK2285403, GSK2298683, and GSK2167542. AUC from time zero to last quantifiable concentration (concn) (AUC\[0-t\]) was determined using the linear trapezoidal rule for increasing concn and the logarithmic trapezoidal rule for decreasing. The AUC from time zero extrapolated to infinity (AUC\[0-inf\] was calculated, where data permit, as the sum of AUC(0-t) and Ct/z, where Ct is the observed plasma concn obtained from the log-linear regression analysis of the last quantifiable time-point and z is the terminal phase rate constant. Area under the concentration-time curve over 12 hr and 24 hr dosing interval is called AUC\[0-12\] and AUC\[0-24\]. AUC(0-inf) was calculated only at Day 1.

Time frame: At pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hr after administration of GSK2118436 + GSK1120212 on Day 1 (single dose) and at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hr on Day 21 (repeat dose)

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).

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Duration of Response

Duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause among participants with confirmed CR or PR. The participant who showed a CR or PR was included in the analysis of duration of response. Duration of response was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.

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

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.

Arm	Measure	Group	Value (MEDIAN)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Duration of Response	Investigator-Assessed, n=5	NA Weeks
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Duration of Response	BICR-Assessed, n=3	NA Weeks

Secondary

Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen binds to hemoglobin in red blood cells when moving through the lungs. A pulse oximeter uses two frequencies of light (red and infrared) to determine the percentage of hemoglobin in the blood that is saturated with oxygen, that is called as blood oxygen saturation, or SpO2. Change from Baseline was calculated as the individual post-Baseline value (Days 8 and 15; Weeks 3 to 132 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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

Secondary

Phase II: Change From Baseline in Weight at the Indicated Time Points

Mean change in body weight from baseline was determined. Change from Baseline was calculated as the individual post-Baseline value (Weeks 3 to 132 and post-treatment Visit) minus the Baseline value. The Baseline value is defined as the last pre-treatment value observed.

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

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

Arm	Measure	Group	Value (MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 3, n=6	-0.68 Kg	Standard Deviation 0.538
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 8, n=6	-0.22 Kg	Standard Deviation 0.553
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 12, n=6	-0.30 Kg	Standard Deviation 1.273
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 16, n=6	0.05 Kg	Standard Deviation 1.947
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 20, n=5	-0.32 Kg	Standard Deviation 2.318
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 24, n=5	0.06 Kg	Standard Deviation 2.243
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 28, n=5	0.18 Kg	Standard Deviation 2.5
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 32, n=5	0.42 Kg	Standard Deviation 2.607
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 36, n=5	0.98 Kg	Standard Deviation 3.016
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 40, n=5	0.62 Kg	Standard Deviation 2.734
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 44, n=4	0.80 Kg	Standard Deviation 3.79
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 48, n=4	0.68 Kg	Standard Deviation 3.527
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 52, n=3	1.27 Kg	Standard Deviation 3.993
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 56, n=3	2.23 Kg	Standard Deviation 3.932
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 60, n=3	2.83 Kg	Standard Deviation 3.879
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 64, n=3	2.70 Kg	Standard Deviation 4.246
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 68, n=3	2.87 Kg	Standard Deviation 4.143
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 72, n=3	2.87 Kg	Standard Deviation 4.165
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 76, n=3	3.63 Kg	Standard Deviation 2.793
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 80, n=3	3.43 Kg	Standard Deviation 4.007
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 84, n=3	4.37 Kg	Standard Deviation 4.008
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 88, n=3	3.80 Kg	Standard Deviation 3.905
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 92, n=3	4.13 Kg	Standard Deviation 3.496
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 96, n=3	4.13 Kg	Standard Deviation 3.63
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 100, n=3	3.53 Kg	Standard Deviation 3.219
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 104, n=3	4.00 Kg	Standard Deviation 4.557
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 108, n=3	3.93 Kg	Standard Deviation 4.8
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 112, n=3	3.60 Kg	Standard Deviation 4.649
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 116, n=3	4.20 Kg	Standard Deviation 4.859
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 120, n=2	5.95 Kg	Standard Deviation 2.192
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 124, n=1	7.50 Kg	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 128, n=1	5.80 Kg	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Week 132, n=1	5.30 Kg	—
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Change From Baseline in Weight at the Indicated Time Points	Post-Treatment, n=3	0.13 Kg	Standard Deviation 2.155

Secondary

Phase II: Duration of Response

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

Arm	Measure	Group	Value (MEDIAN)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Duration of Response	Investigator-Assessed, n=5	NA Weeks
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Duration of Response	BICR-Assessed, n=5	NA Weeks

Secondary

Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event

An AE is defined as any untoward MO in a part. temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. SAE is defined as any untoward MO that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, a congenital anomaly/birth defect and protocol-specific SAEs:ALT\>=3xULN and bilirubin\>=2xULN(\>35% direct) (or ALT\>=3xULN, international normalized ratio\>1.5), any new primary cancers, treatment emergent malignancies except basal cell carcinoma, symptomatic or asymptomatic LVEF decrease, retinal pigment epithelial detachment or retinal vein occlusion, pyrexia with hypotension,or dehydration or renal insufficiency,or severe (\>=G3) rigor/chills.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event	Any AE	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event	Any SAE	0 Participants

Secondary

Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points

Single 12-lead ECGs were performed at Baseline, Weeks 3 to 132 and post-treatment Visit. ECG findings were categorized as: normal, abnormal - CS, or abnormal - NCS, as determined by the investigator.

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

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

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

Secondary

Phase II: Number of Participants With the Indicated Urinalysis Results

Urine samples were collected for urine dipstick analysis at Baseline and at the post-treatment Visit. The number of participants with negative (absence) and positive (presence: trace, 1+, 2+, 3+, 4+ or 5+) results for UOB, UGLU, UKET, UP and UUBIL were summarized. The Baseline value is defined as the last pre-treatment value observed.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UOB, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UOB, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UOB, Post-Treatment, Negative	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UOB, Post-Treatment, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UGLU, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UGLU, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UGLU, Post-Treatment, Negative	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UGLU, Post-Treatment, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UKET, Baseline, Negative	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UKET, Baseline, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UKET, Post-Treatment, Negative	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UKET, Post-Treatment, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UP, Baseline, Negative	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UP, Baseline, Positive	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UP, Post-Treatment, Negative	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UP, Post-Treatment, Positive	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UUBIL, Baseline, Negative	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UUBIL, Baseline, Positive	6 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UUBIL, Post-Treatment, Negative	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Urinalysis Results	UUBIL, Post-Treatment, Positive	3 Participants

Secondary

Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters

CCPs were graded according to NCI CTCAE garde version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline grade occurred. CCPs that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. CCPs included: albumin, alkaline phosphatase, ALT, AST, total bilirubin, calcium, creatinine, glucose, potassium, magnesium, sodium, inorganic phosphorus, chloride, LDH, total protein, urea/BUN and uric acid.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters	Chloride, High	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters	LDH, High	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters

Hematology parameters were summarized according to NCI CTCAE G, version 4.0 as: G1, Mild; G2, Moderate; G3, Severe; G4, Life-threatening or disabling; G5, Death. Data are presented for only those parameters for which an increase to G3 or G4 from Baseline G occurred. For hematology parameters that were not graded according to NCI CTCAE criteria, were categorized as High and Low with respect to the normal range. Data are presented only for those parameters for which the category decreased to Low or increased to High relative to the Baseline category. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Hematology parameters included: hemoglobin, lymphocytes, total neutrophils, platelet count, WBC counts, basophils, eosinophils, hematocrit, MCHC, MCH, MCV, monocytes and RBC count.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Total Neutrophils, G3	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Eosinophils, High	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Hematocrit, Low	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCHC, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCH, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCV, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	MCV, High	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Monocytes, Low	3 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	Monocytes, High	4 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	RBC count, Low	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters	RBC count, High	1 Participants

Secondary

Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status

The ECOG pef status 5-point scale is used to assess how a participant's disease is progressing, to assess how the disease affects the daily living abilities of the par. and to determine appropriate treatment and prognosis: G0, fully active, able to carry on all pre-disease pef without restriction. G1, restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, example, light house work, office work. G2, ambulatory and capable of all selfcare, but unable to carry out any work activities; up and about \>50% of waking hrs. G3, capable of only limited selfcare; confined to bed or chair \>50% of waking hrs. G4, completely disabled; cannot carry on any selfcare; totally confined to bed or chair. G5, dead. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. Number of par. who improved, had no change, or deteriorated in pef status from BL is summarized.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status	Improved	0 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status	No change	4 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status	Deteriorated	2 Participants

Secondary

Phase II: Number of Participants With Unconfirmed Overall Response

ORR is defined as the percentage of participants with an unconfirmed CR or PR according to RECIST version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve (respond), stay the same (stabilize), or worsen (progress) during treatment. CR is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). Unconfirmed ORR was assessed by investigator and BICR.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Unconfirmed Overall Response	Investigator-Assessed	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Unconfirmed Overall Response	BICR-Assessed	5 Participants

p-value: <0.000195% CI: [35.9, 99.6]Exact binomial test

Secondary

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate

Change from Baseline in heart rate is categorized as decrease to \<60 bpm, change to normal or no change, and increase to \>100 bpm relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant's heart rate value decreased to \<60 bpm and increased to \>100 bpm post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	Decrease to <60 bpm	1 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate	Increase to >100 bpm	1 Participants

Secondary

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram

Absolute change from Baseline in LVEF were summarized at each scheduled assessment time and in the worst-case post Baseline. Only the post Baseline assessments that used the same method (ECHO or MUGA) as the Baseline assessments were used to derive the change from Baseline. The change from Baseline was categorized as: any increase; no change; 0-\<10 Decrease, 10-19 Decrease, \>=20 Decrease, \>=10 Decrease and \>= LLN, \>=10 Decrease and below LLN, \>=20 Decrease and \>=LLN and \>=20 Decrease and below LLN. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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

Secondary

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature

Change from Baseline in temperature is categorized as a decrease to \<=35 degrees C, change to normal or no change as 35-38 degrees C, and increase to \>=38 degrees C relative to the Baseline value. Participants with a missing Baseline value are assumed to have a normal Baseline value. Participants were counted twice if the participant temperature value decreased to \<=35 degrees C and increased to \>=38 degrees C post-Baseline. The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	Decrease to <=35 degrees C	2 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	Change to normal or no change	4 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature	Increase to >=38 degrees C	0 Participants

Secondary

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 and DBP values were graded using (NCI CTCAE version 4.0). SBP was categorized as: G1 (Increase to \>=120 to 140 mmHg), G2 (Increase to \>=140 to \<160 mmHg), and G3 (Increase to \>=160 mmHg). DBP was categorized as: G1 (Increase to \>=80 to \<90 mmHg), G2 (Increase to \>=90 to \<100 mmHg), and G3 (Increase to \>=100 mmHg). The worst-case during the on-therapy period was determined taking into account both scheduled and unscheduled assessments. An increase is defined as an increase in the CTCAE grade relative to the Baseline grade. Participants with missing Baseline values were assumed to have a Baseline value of G0.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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 I: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase II: Progression Free Survival (PFS)

PFS is defined as the time from the first dose of study treatment to the earliest date of disease progression or death due to any cause. The length of this interval is estimated as the date of death or disease progression minus the date of first dose plus one day. The date of documented disease progression is defined as the date of disease progression based on radiologic evidence. Participants with documented date of disease progresssion or death and who had not received subsequent anticancer treatment prior to the date of documented disease progression or death were included in the analysis of PFS. PFS was assessed by investigator and BICR. Please note the values of the Full Range (min, max) are described irregardless of censoring at data cut-off.

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

Arm	Measure	Group	Value (MEDIAN)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Progression Free Survival (PFS)	Investigator-Assessed, n=6	NA Weeks
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase II: Progression Free Survival (PFS)	BICR-Assessed, n=6	NA Weeks

Secondary

Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose

Population: PK Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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

Phase I: Number of Participants With Confirmed Overall Response Rate

Confirmed ORR is defined as the percentage of participants with a confirmed CR or PR according to RECIST, version 1.1. RECIST is a set of rules that define when tumors in cancer participants improve (respond), stay the same (stabilize), or worsen (progress) during treatment. CR is defined as the disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions after treatment from Baseline (before study drug administration). ORR was assessed by investigator and BICR.

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Confirmed Overall Response Rate	Investigator-Assessed	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Confirmed Overall Response Rate	BICR-Assessed	3 Participants

p-value: <0.000195% CI: [35.9, 99.6]Exact binomial test

p-value: 0.015895% CI: [11.8, 82.2]Exact binomial test

Secondary

Phase I: Number of Participants With Unconfirmed Overall Response Rate

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

Population: ATS Population

Arm	Measure	Group	Value (NUMBER)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Unconfirmed Overall Response Rate	Investigator-Assessed	5 Participants
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Number of Participants With Unconfirmed Overall Response Rate	BICR-Assessed	3 Participants

p-value: <0.000195% CI: [35.9, 99.6]Exact binomial test

p-value: 0.015895% CI: [11.8, 88.2]Exact binomial test

Secondary

Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose

Trough concentration is the lowest level that a drug is present in the body. Pre-dose (trough) blood samples were collected on Day 8, Day 15, Weeks 3, 8, 16 and 24 for estimating plasma trough concentration. GSK2118436 metabolites included GSK2285403, GSK2298683, and GSK2167542. Ctau was determined from the raw concentration-time data.

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

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

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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

Secondary

Phase I: Progression Free Survival (PFS)

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

Arm	Measure	Group	Value (MEDIAN)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Progression Free Survival (PFS)	Investigator-Assessed, n=6	NA Weeks
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	Phase I: Progression Free Survival (PFS)	BICR-Assessed, n=6	NA Weeks

Secondary

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

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.

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

Arm	Measure	Group	Value (MEDIAN)
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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
Phase I: GSK2118436 150 mg + GSK1120212 2 mg	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

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

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Study design

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Primary

Secondary

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Baseline characteristics

Adverse events

Outcome results

Phase I: Change From Baseline in Oxygen Saturation (SpO2) Measured Via Pulse Oxymetry at the Indicated Time Points

Phase I: Change From Baseline in Weight at the Indicated Time Points

Phase II: Number of Participant With Confirmed Overall Response

Phase I: Number of Participants With a Dose-limiting Toxicity (DLT)

Phase I: Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Event (SAE)

Phase I: Number of Participants With the Indicated Electrocardiogram (ECG) Findings at the Indicated Time Points

Phase I: Number of Participants With the Indicated Urinalysis Parameters

Phase I: Number of Participants With the Indicated Worst-case Change From Baseline (BL) in the Indicated Clinical Chemistry Parameters (CCPs)

Phase I: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters

Phase I: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance (Pef) Status

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Assessed by Echocardiogram (ECHO)

Phase I: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature

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

Phase I: Area Under the Plasma Concentration Versus Time Curve (AUC) of GSK2118436 and Metabolites, and GSK1120212 After Single and Repeat Dose

Phase I: Duration of Response

Phase II: Change From Baseline in Oxygen Saturation Measured Via Pulse Oxymetry at the Indicated Time Points

Phase II: Change From Baseline in Weight at the Indicated Time Points

Phase II: Duration of Response

Phase II: Number of Participants With Any Adverse Event and Any Serious Adverse Event

Phase II: Number of Participants With the Indicated Electrocardiogram Findings at the Indicated Time Points

Phase II: Number of Participants With the Indicated Urinalysis Results

Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Clinical Chemistry Parameters

Phase II: Number of Participants With the Indicated Worst-case Change From Baseline in the Indicated Hematology Parameters

Phase II: Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in ECOG Perormance Status

Phase II: Number of Participants With Unconfirmed Overall Response

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Heart Rate

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Left Ventricular Ejection Fraction as Assessed by Echocardiogram

Phase II: Number of Participants With Worst-case On-therapy Change From Baseline in Temperature

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

Phase II: Progression Free Survival (PFS)

Phase I: Maximum Plasma Concentration (Cmax) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose

Phase I: Number of Participants With Confirmed Overall Response Rate

Phase I: Number of Participants With Unconfirmed Overall Response Rate

Phase I: Plasma Trough Concentration (Ctau) of GSK2118436 and Metabolites, and GSK1120212 After a Single and Repeat Dose

Phase I: Progression Free Survival (PFS)

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