An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as alanine aminotransferase (ALT) >=3 times upper limit of normal (ULN), and bilirubin >=2 times ULN (>35 percent [%] direct) (or ALT >=3 times ULN and international normalized ratio (INR) >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.

All Treated Safety Population consisted of all participants who received at least one dose of Enzalutamide.

An AE is any untoward medical occurrence in a participant or clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, protocol-specific SAEs: All events of possible study treatment-induced liver injury with hyperbilirubinemia defined as ALT >=3 times ULN, and bilirubin >=2 times ULN (>35% direct) (or ALT >=3 times ULN and INR >1.5 if INR is measured) or termed 'Hy's Law' events (INR measurement is not required and the threshold value stated did not apply to participants receiving anticoagulants) or any new primary cancer.

All Treated Safety Population consisted of all participants who received at least one dose of GSK2636771 or Enzalutamide. Only those participants with data available at the indicated time points were analyzed.

An event was considered as DLT if the event was attributed (definitely, probably or possibly) to study treatment, occured within the first 28 days of combination treatment (DLT reporting period), and met one of the following criteria: Febrile neutropenia of any grade or duration as per Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 4 neutropenia lasting >5 days, Grade 3 or greater non-hematologic toxicity that cannot be controlled with routine supportive measures, Grade 4 thrombocytopenia, ALT >3 times ULN with bilirubin >2 times ULN or ALT >=3 times ULN and >=1.5 times Baseline ALT value, if enrolled with liver metastases/tumor infiltration at Baseline), together with bilirubin >=2 times ULN.

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected to analyze the hematology parameters: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), monocytes, total neutrophils, platelet count and white blood cells (WBCs) count. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the hematology parameters: INR, PT and PTT. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: ALT, Albumin, Alkaline phosphatase (ALP), Aspartate amino transferase (AST), Calcium, Carbon dioxide (CO2), Chloride, Creatinine, Direct bilirubin, Glucose, Lactate dehydrogenase, Magnesium, Potassium, Sodium, Total bilirubin and Total protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected to analyze the chemistry parameters: BUN and uric acid. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Urine samples were collected to analyze the urinalysis parameters: Calcium, Creatinine concentration (conc), Magnesium, Phosphate and Protein. Baseline value is the latest GSK2636771 pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Percent change from Baseline was calculated as 100 multiplied by (post-Baseline visit value minus Baseline divided by Baseline).

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

A 12-lead ECG was obtained after the participant had rested at least 5 minutes in a semi-recumbent or supine position at each time point during the study using ECG machine that automatically measured PR, QRS, QT and Corrected QT interval (QT duration corrected for heart rate by Bazett's formula [QTcB] and Fridericia's formula [QTcF]). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with abnormal clinical significant ECG findings are presented.

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

SBP and DBP were measured after resting for 5 minutes in semi-supine position. SBP and DBP were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. 'Any grade increase' is defined as an increase in CTCAE grade relative to Baseline grade. For SBP, Grade 0: <120 millimeters of mercury [mmHg]), Grade 1: 120-139 mmHg, Grade 2: 140-159 mmHg, Grade 3:>=160 mmHg. For DBP, Grade 0: <80 mmHg, Grade 1: 80-89 mmHg, Grade 2: 90-99 mmHg, Grade 3: >=100 mmHg. Higher grade indicate worst outcome. Data for worst-case post-Baseline is reported.

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed.

Heart rate was measured after resting for 5 minutes in semi-supine position. The clinical concern range for heart rate was: low: decrease to <60 beats per minute (bpm) and high: increase to >100 bpm. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decrease to <60 bpm' and 'increase to >100 bpm' during post-Baseline visits. Data for worst case post-Baseline is reported.

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed.

Temperature was measured after resting for 5 minutes in semi-supine position. The clinical concern range for body temperature was: low: decrease to <=35 degrees celsius, high: increase to >=38 degrees celsius. Participants were counted in the worst case category that their value changed to (low, within range or no change, or high) unless there was no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the 'Change to normal or No Change' category. Participants were counted twice if the participant had both values 'decreased to <=35 degree celsius' and 'increased to >=38 degrees celsius' during post-Baseline visits. Data for worst-case post-Baseline is presented.

All Treated Safety Population. Only those participants with data available at the indicated time points were analyzed.

The 12-week non-PD rate was defined as percentage of participants without progression(non-PD) at Week12 as determined from Prostate-specific antigen(PSA) results, radiographic assessment per Response Evaluation Criteria In Solid Tumors(RECIST)1.1 and bone scan.Disease progression was defined by 1 or more of the following:PSA progression alone; PSA progression according to the PCWG2 criteria with accompanying progression by RECIST1.1 or bone scan for participants with soft tissue Baseline disease; Bone progression on bone scan according to PCWG2 criteria; or Radiographic progression in soft tissue or bone by RECIST1.1 for participants with Baseline disease.Modified All Treated Clinical Activity Population consisted of all participants who received at least 1 dose of GSK2636771 and who were treated at the same dose as dose expansion cohort and have been on study drug for at least 12weeks or have discontinued study treatment due to disease progression, died or withdrawn for any reason.

Modified All Treated Clinical Activity Population. The hypothesis for 12-week non-PD rate was to be tested on a combination of data provided in the dose escalation and dose expansion phase. The 200 mg dose was the only one that had a dose expansion phase. Hence, a combined arm of GSK2636771 200 mg/ Enzalutamide 160 mg has been presented.

PSA50 response rate is defined as percentage of participants with a decrease of >=50% in the PSA concentration from the Baseline PSA value determined at least 12 weeks after start of treatment until last post-treatment follow-up visit or initiation of new anti-cancer therapy and confirmed after 3 or more weeks by an additional PSA evaluation. Confirmed PSA50 is defined as decline of >=50% in PSA concentration from Baseline.

All treated Clinical Activity Population consisted of all participants who received at least one dose of GSK2636771.

ORR is defined as the percentage of participants with a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per RECIST Version (v) 1.1 criteria; where CR: Disappearance of all target lesions; PR: at least 30% decrease in the sum of the longest diameter of target lesions with reference to Baseline sum of diameters.

All Treated Clinical Activity Population

Time to PSA progression is defined as the time from combination study treatment start until the first PSA progression per PCWG2 criteria (confirmed if there has been a PSA decline from Baseline). Time to PSA was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.

All treated Clinical Activity Population. Only those participants with data available at the indicated time points were analyzed.

Time to radiological progression is defined as the time from combination study treatment start until the first radiological progression by PCWG2 criteria. Time to radiological progession was analyzed using Kaplan-Meier methods. For participants who do not progress, participants were censored at the time of last radiological scan or date of death. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. Median and inter-quartile range (first and third quartile) are presented.

All treated Clinical Activity Population. Only those participants with data available at the indicated time points were analyzed.

rPFS is defined as the interval of time (in weeks) between the date of first dose of GSK2636771 and the earlier of the date of disease progression as assessed by the investigator per RECIST version 1.1 criteria and the date of death due to any cause. For participants who do not progress or die, participants were censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of GSK2636771 drug. rPFS was analyzed using Kaplan-Meier methods. Median and inter-quartile range (first and third quartile) are presented.

All treated Clinical Activity Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK2636771. Pharmacokinetic Concentration Population consisted of all participants in the All Treated Safety Population for whom a blood sample for pharmacokinetics were obtained, analyzed, and was measurable.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles). Blood samples were not collected for analysis of Enzalutamide for GSK2636771 400mg/Enzalutamide 160mg Escalation arm.

Blood samples were collected at indicated time points for pharmacokinetic analysis of enzalutamide.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).

Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles). Blood samples were not collected for analysis of Enzalutamide for GSK2636771 400mg/Enzalutamide 160mg Escalation arm.

Blood samples were collected at indicated time points for pharmacokinetic analysis of N-desmethyl enzalutamide.

Pharmacokinetic Concentration Population. Only those participants with data available at the indicated time points were analyzed (represented by n= X in the category titles).