Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma

A Phase I Open-label, Dose Escalation Study to Investigate The Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma

Status

Terminated

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02034123

Enrollment

Registered

2014-01-13

Start date

2014-02-04

Completion date

2017-04-18

Last updated

2019-12-06

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

Conditions

Carcinoma, Small Cell

Keywords

First time in humans, Small cell lung carcinoma, Oncology, GSK2879552, LSD1 inhibitor

Brief summary

GSK2879552 is a potent, selective, mechanism-based inactivator of Lysine Specific Demethylase 1 (LSD1)/ CoRepressor for Element-1-Silencing Transcription factor (CoREST) activity. This is a phase I, open-label, multi-center, non-randomized, 2-part first time in human (FTIH) study for GSK2879552. Part 1 is a dose escalation phase to determine the recommended phase 2 dose (RP2D) for GSK2879552 based on the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) profiles observed after oral administration of GSK2879552. Any dose level(s) may be expanded up to 12 subjects in order to collect additional data on PK and PD.The safety and PK/PD data will be reviewed prior to the dose decision, and the dose escalation will be guided by the Neuenschwander -continuous reassessment method (N-CRM). Built-in safety constraints are in place to prevent exposing subjects to undue risk of toxicity. Once RP2D is identified, an expansion cohort (Part 2) of up to 30 subjects will be enrolled to further evaluate the clinical activity and tolerability of GSK2879552 in subjects with relapsed/refractory SCLC.

Interventions

DRUGGSK2879552

Subjects will receive GSK2879552orally with approximately 200 milliliter (mL) of water.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Provided signed written informed consent * Males and females \>=18 years of age (at the time consent is obtained). * Histologically or cytologically confirmed diagnosis of small cell lung carcinoma. Subjects must have measurable disease per RECIST 1.1 (for Part 2 only). * Recurrent or refractory disease after receiving at least one prior standard/approved platinum-containing chemotherapy regimen, or where standard therapy is refused. Part 2 only: Subjects must have recurrent disease after receiving a maximum of two prior chemotherapy regimens including at least one platinum containing regimen. * Eastern Cooperative Oncology Group (ECOG) performance status of \<= 1. (ECOG performance status of 0 or 1). * Tumor tissue requirements: Availability of archival tissue, or willingness to undergo fresh biopsy at baseline; Enrollment in PK/PD cohort may be limited to subjects with disease amenable to pre- and post-dose biopsies, and willingness to undergo biopsy. * All prior treatment-related toxicities must be National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 \<=Grade 1 at the time of enrollment (except for alopecia) * Adequate baseline organ function * Women of childbearing potential must have a negative serum pregnancy test within 7 days of first dose of study treatment and agree to use effective contraception, as defined in protocol, during the study and for 7 days following the last dose of study treatment. * Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception as described in protocol from the administration of the first dose of study treatment until 3 months after the last dose of study treatment to allow for clearance of any altered sperm. * Able to swallow and retain orally administered study treatment and does not have any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels. * French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion criteria

* Concurrent malignancy other than SCLC. History of other malignancy is allowed as long as there is no evidence of active disease or need for treatment. * Currently receiving anti-cancer therapy. Exceptions: Zoledronic acid and denosumab to treat bone metastasis are allowed. * Prior treatment with temozolomide, dacarbazine or procarbazine. * Prior treatment with poly ADP ribose polymerase (PARP) inhibitors (e.g., olaparib, ABT-888). * Baseline Montreal Cognitive Assessment (MOCA) score of 22 or lower. * Received major surgery, radiotherapy, or immunotherapy within 4 weeks of GSK2879552 administration. Chemotherapy regimens with delayed toxicity within the last four weeks (six weeks for prior nitrosourea or mitomycin C). Chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity or palliative radiation to a limited area within the last two weeks. * Administration of an investigational drug within 28 days or 5 half-lives, whichever is shorter preceding the first dose of study treatment(s) in this study. * French subjects: The French subject has participated in any study using an investigational study treatment(s) during the previous 28 days. * Subjects with current/a history of bleeding disorder or coagulopathy or who are at particularly high risk for bleeding complications. * Requiring anticoagulants at therapeutic doses or platelet inhibitor. * Current use of a prohibited medication or expected to require any of these medications during treatment with the investigational drug * Evidence of severe or uncontrolled systemic diseases. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the investigator * Known active Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infections. Subjects with laboratory evidence of HBV clearance may be enrolled * Leptomeningeal metastases or spinal cord compression due to disease. * Subjects with previously untreated or uncontrolled brain metastases. * Cardiac abnormalities * Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to GSK2879552 or LSD1 inhibitors that contraindicates their participation. * Lactating female * Consumption of Seville oranges, grapefruit, grapefruit hybrids, grapefruit juice, pommelos, or exotic citrus fruits, from 1 day prior to the first dose of study treatment(s) until the last dose of study drug.

Design outcomes

Primary

Measure	Time frame	Description
Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Median of 7.286 weeks of drug exposure	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Treated Population which included all participants who received at least one dose of study treatment.
Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	Median of 7.286 weeks of drug exposure	An event was considered a DLT if it occurs within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting \> 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia \> 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting \> 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity.
Part 1: Number of Participants With Dose Reduction or Delays	Median of 7.286 weeks of drug exposure	The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.
Part 1: Number of Participants Withdrawn Due to Toxicities	Median of 7.286 weeks of drug exposure	Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.
Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Baseline and median of 7.286 weeks of drug exposure	Blood samples were collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyl transferase (GGT), albumin, sodium, calcium, alkaline phosphatase, and phosphorus, inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in clinical chemistry parameters have been presented. The clinical chemistry parameters for which any grade increase worst-case on-therapy value was reported have been only summarized. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Baseline and median of 7.286 weeks of drug exposure	Blood samples were collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented. The hematology parameters for which any grade increase worst-case on-therapy value was reported have been only summarized.
Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	Median of 7.286 weeks of drug exposure	Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with critical changes in values of vital signs in response to drug have been presented.
Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Median of 7.286 weeks of drug exposure	Single measurements of 12-lead ECGs were obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. The number of participants with abnormal - not clinically significant and abnormal - clinically significant worst-case on-therapy value have been presented.
Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	Median of 7.286 weeks of drug exposure	The complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). All abnormal physical examination findings were reported as AEs within the AE specific case report form (CRF) page. Hence, data was not captured separately for this outcome as number of participants with abnormal findings with respect to physical examinations. NA indicates data was not available as all abnormal physical examination findings were reported as AEs.
Part 2: Number of Participants Achieving Disease Control Rate at Week 16	Week 16	Clinical response was planned to be assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Week 16. Disease control rate was defined as number of participants achieving complete response (CR), partial response (PR) and stable disease (SD) per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Secondary

Measure	Time frame	Description
Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose	Baseline and median of 7.286 weeks of drug exposure	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Estimates and standard error have been presented.
Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax	Baseline and median of 7.286 weeks of drug exposure	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.
Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)	Baseline and median of 7.286 weeks of drug exposure	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.
Part 2: Number of Participants With SAEs and Non-SAEs	Up to 2 years	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants With DLTs	Up to 2 years	An event was considered a DLT if it occured within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting \> 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia \> 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting \> 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants With Dose Reduction or Delays	Up to 2 years	The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants Withdrawn Due to Toxicities	Up to 2 years	Participants were planned to be monitored from start of the study till the development of toxicity in Part 2. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Baseline and up to 2 years	Blood samples were planned to be collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, ALT, uric acid, glucose, GGT, albumin, sodium, calcium, alkaline phosphatase, and phosphorus inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Baseline and up to 2 years	Blood samples were planned to be collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	Up to 2 years	Vital sign measurement includes SBP, DBP, temperature, respiration rate and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 2: Number of Participants With Abnormal Findings Undergoing Physical Examinations	Up to 2 years	The complete physical examination includes assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination includes assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Clearance Following Administration of GSK2879552	Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48	Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including clearance. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Volume of Distribution Following Administration of GSK2879552	Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48	Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including volume of distribution. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose	Baseline and up to 2 years	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax	Baseline and up to 2 years	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)	Baseline and Up to 2 years	The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Duration of Response	Up to 2 years	Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Progression Free Survival (PFS)	Up to 2 years	PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Percentage of Participants Achieving CR and PR	Up to 2 years	Overall response rate is defined as percentage of participants achieving CR and PR per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 2: Number of Participants With Abnormal Findings for ECG Parameters	Up to 2 years	Single measurements of 12-lead ECGs were planned to be obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 15	Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.
Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552 . Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).
Part 1: Accumulation Ratio Following Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	The accumulation ratio was analyzed using analysis of variance (ANOVA) for AUC (0-tau) on Day 15 versus AUC (0-tau) on Day 1 by dose cohort. Only dose cohorts with repeat daily dosing were analyzed. The observed accumulation ratio (Ro) was determined based on AUC data to estimate the extent of accumulation after repeat dosing. The Ro of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the pharmacokinetic parameter between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.
Part 1: Time Invariance Ratio Following Administration of GSK2879552	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15	Time invariance was assessed to evaluate whether the pharmacokinetics remains unaltered after repeat dosing. The mixed effect model was fitted with day as a fixed effect and participant as a random effect for each treatment (dose) separately. AUC (0-tau) on Day 15 was compared to AUC (0-infinity) on Day 1 in order to assess time invariance for each dose. The ratio and 90 percent CI were calculated by back-transforming the difference between the LS means for the two days and associated 90 percent CI, for each dose. Only dose cohorts with repeat daily dosing were analyzed.
Part 1: Number of Participants Achieving Disease Control Rate at Week 16	Week 16	The clinical activity of GSK2879552 given orally in participants with SCLC was evaluated by assessing disease control rate. Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate (CR+PR+SD) based on RECIST version 1.1 at Week 16. Disease control rate was defined as number of participants achieving CR, PR and SD per RECIST version 1.1. The number of participants achieving disease control rate have been presented.

Countries

France, Spain, United States

Participant flow

Recruitment details

This was planned as a 2-part, first time in human study in participants with relapsed/refractory small cell lung carcinoma. Part 1 was a dose escalation cohort and Part 2 was an expansion cohort. Participants were planned to receive GSK2879552 at a starting dose of 0.25 milligrams (mg) once daily for 28 days.

Pre-assignment details

This study was terminated early during Part 1 as the risk benefit in relapsed refractory SCLC did not favor continuation of the study. Data was collected only in Part 1 and no participants were enrolled in Part 2. A total of 29 participants enrolled and received treatment in Part 1. Of which 7 prematurely withdrawn and 22 completed study.

Participants by arm

Arm	Count
Part 1:GSK2879552 0.25 mg Daily Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	1
Part 1:GSK2879552 0.5 mg Daily Participants received GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	1
Part 1:GSK2879552 1.0 mg Daily Participants received GSK2879552 with a dose of 1.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	5
Part 1:GSK2879552 1.5 mg Daily Participants received GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	3
Part 1: GSK2879552 2.0 mg Daily Participants received GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	7
Part 1: GSK2879552 3.0 mg Daily Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	3
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	2
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off Participants received GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	5
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off Participants received GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	2
Part 2:GSK2879552 0.25 mg Daily Participants were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2:GSK2879552 0.5 mg Daily Participants were planned to receive GSK2879552 with a dose of 0.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2:GSK2879552 1.0 mg Daily Participants were planned to receive GSK2879552 with a dose of 1 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2:GSK2879552 1.5 mg Daily Participants were planned to receive GSK2879552 with a dose of 1.5 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2: GSK2879552 2.0 mg Daily Participants were planned to receive GSK2879552 with a dose of 2.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2: GSK2879552 3.0 mg Daily Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.	0
Part 2: GSK2879552 3.0 mg 4 Days on/3 Days Off Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 3 days.	0
Part 2: GSK2879552 3.0 mg 4 Days on/10 Days Off Participants were planned to receive GSK2879552 with a dose of 3.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	0
Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off Participants were planned to receive GSK2879552 with a dose of 4.0 mg once daily, administered orally with approximately 200 milliliter of water for 4 days during the treatment period following buffer period of 10 days.	0
Total	29

Withdrawals & dropouts

Period	Reason	FG003	FG004	FG007	FG008
Part1(Median of 7.286 Weeks of Exposure)	Adverse Event	0	1	1	1
Part1(Median of 7.286 Weeks of Exposure)	Lack of Efficacy	1	0	0	0
Part1(Median of 7.286 Weeks of Exposure)	Other-Study closed/terminated	0	0	0	1
Part1(Median of 7.286 Weeks of Exposure)	Withdrawal by Subject	1	1	0	0

Baseline characteristics

Characteristic	Part 1:GSK2879552 0.25 mg Daily	Part 1:GSK2879552 0.5 mg Daily	Part 1:GSK2879552 1.0 mg Daily	Part 1:GSK2879552 1.5 mg Daily	Part 1: GSK2879552 2.0 mg Daily	Part 1: GSK2879552 3.0 mg Daily	Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Total
Age, Continuous	78.0 Years	47.0 Years	63.8 Years STANDARD_DEVIATION 4.09	56.7 Years STANDARD_DEVIATION 8.08	62.4 Years STANDARD_DEVIATION 7.41	60.3 Years STANDARD_DEVIATION 7.51	53.5 Years STANDARD_DEVIATION 13.44	58.8 Years STANDARD_DEVIATION 10.33	61.5 Years STANDARD_DEVIATION 9.19	60.6 Years STANDARD_DEVIATION 8.58
Race/Ethnicity, Customized African American/African Heritage	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized White-White/Caucasian/European Heritage	1 Participants	1 Participants	5 Participants	3 Participants	7 Participants	3 Participants	1 Participants	5 Participants	2 Participants	28 Participants
Sex: Female, Male Female	1 Participants	1 Participants	1 Participants	0 Participants	1 Participants	2 Participants	1 Participants	3 Participants	1 Participants	11 Participants
Sex: Female, Male Male	0 Participants	0 Participants	4 Participants	3 Participants	6 Participants	1 Participants	1 Participants	2 Participants	1 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk	EG012 affected / at risk	EG013 affected / at risk	EG014 affected / at risk	EG015 affected / at risk	EG016 affected / at risk	EG017 affected / at risk
deaths Total, all-cause mortality	0 / 1	0 / 1	0 / 5	0 / 3	1 / 7	0 / 3	0 / 2	0 / 5	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
other Total, other adverse events	1 / 1	1 / 1	5 / 5	2 / 3	6 / 7	3 / 3	2 / 2	5 / 5	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
serious Total, serious adverse events	0 / 1	0 / 1	0 / 5	2 / 3	2 / 7	1 / 3	0 / 2	2 / 5	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Outcome results

Primary

Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters

Single measurements of 12-lead ECGs were obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. The number of participants with abnormal - not clinically significant and abnormal - clinically significant worst-case on-therapy value have been presented.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Group	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	4 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	4 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	5 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - not clinically significant	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters	Abnormal - clinically significant	0 Participants

Primary

Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations

The complete physical examination included assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination included assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). All abnormal physical examination findings were reported as AEs within the AE specific case report form (CRF) page. Hence, data was not captured separately for this outcome as number of participants with abnormal findings with respect to physical examinations. NA indicates data was not available as all abnormal physical examination findings were reported as AEs.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations	NA Participants

Primary

Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline

Blood samples were collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyl transferase (GGT), albumin, sodium, calcium, alkaline phosphatase, and phosphorus, inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in clinical chemistry parameters have been presented. The clinical chemistry parameters for which any grade increase worst-case on-therapy value was reported have been only summarized. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Baseline and median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Group	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	4 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Uric acid;n=0,0,1,0,0,1,0,0,1	1 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	4 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	4 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	4 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	4 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	3 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Uric acid;n=0,0,1,0,0,1,0,0,1	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	2 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Calcium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Total Bilirubin;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Albumin;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	AST;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose;n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	ALT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium;n=1,1,5,2,5,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	GGT;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Creatinine;n=1,1,5,3,5,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Uric acid;n=0,0,1,0,0,1,0,0,1	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline	Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2	0 Participants

Primary

Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline

Blood samples were collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented. The hematology parameters for which any grade increase worst-case on-therapy value was reported have been only summarized.

Time frame: Baseline and median of 7.286 weeks of drug exposure

Population: All Treated Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Group	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	0 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	2 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	3 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	1 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	4 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	4 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	5 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	3 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	4 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	4 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	4 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	3 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Increased)	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes (Decreased)	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Anemia)	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Total Neutrophils	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin (Increased)	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Platelet count	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Hemoglobin	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	WBC count	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline	Lymphocytes	1 Participants

Primary

Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug

Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. Vital signs were measured after resting for at least 5 minutes in a semi-supine position. The number of participants with critical changes in values of vital signs in response to drug have been presented.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug	0 Participants

Primary

Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

An event was considered a DLT if it occurs within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting \> 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia \> 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting \> 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Dose Limiting Toxicities (DLT)	0 Participants

Primary

Part 1: Number of Participants With Dose Reduction or Delays

The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	3 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Dose Reduction or Delays	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Dose Reduction or Delays	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Dose Reduction or Delays	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Dose Reduction or Delays	0 Participants

Primary

Part 1: Number of Participants Withdrawn Due to Toxicities

Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants Withdrawn Due to Toxicities	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants Withdrawn Due to Toxicities	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants Withdrawn Due to Toxicities	1 Participants

Primary

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. The analysis was performed on All Treated Population which included all participants who received at least one dose of study treatment.

Time frame: Median of 7.286 weeks of drug exposure

Population: All Treated Population

Arm	Measure	Group	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	1 Participants
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	0 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	5 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	2 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	2 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	6 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	2 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	3 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	0 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	2 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	5 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	2 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any non-SAE	1 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs	Any SAE	2 Participants

Primary

Part 2: Number of Participants Achieving Disease Control Rate at Week 16

Clinical response was planned to be assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Week 16. Disease control rate was defined as number of participants achieving complete response (CR), partial response (PR) and stable disease (SD) per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Week 16

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 1: Accumulation Ratio Following Administration of GSK2879552

The accumulation ratio was analyzed using analysis of variance (ANOVA) for AUC (0-tau) on Day 15 versus AUC (0-tau) on Day 1 by dose cohort. Only dose cohorts with repeat daily dosing were analyzed. The observed accumulation ratio (Ro) was determined based on AUC data to estimate the extent of accumulation after repeat dosing. The Ro of GSK2879552 was estimated by calculating the ratio of the geometric least squares (GLS) means of the pharmacokinetic parameter between Day 15 and Day 1 for all dose levels and the corresponding 90 percent confidence interval (CI) for each ratio.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Accumulation Ratio Following Administration of GSK2879552	1.917 Ratio of AUC
Part 1:GSK2879552 0.5 mg Daily	Part 1: Accumulation Ratio Following Administration of GSK2879552	1.652 Ratio of AUC

Secondary

Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including lambda z following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552 . Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 Hours^-1	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 Hours^-1	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 Hours^-1	Geometric Coefficient of Variation 62.6
Part 1:GSK2879552 1.5 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.1 Hours^-1	Geometric Coefficient of Variation 8.7
Part 1: GSK2879552 2.0 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 Hours^-1	Geometric Coefficient of Variation 8.7
Part 1: GSK2879552 3.0 mg Daily	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.0 Hours^-1	Geometric Coefficient of Variation 19.1
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.1 Hours^-1	Geometric Coefficient of Variation 47.9
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.1 Hours^-1	Geometric Coefficient of Variation 23.2
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1	0.1 Hours^-1	—

Secondary

Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including T1/2 following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. The data for Day 15 was not computed due to the long half-life of GSK2879552. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	16.9 Hours	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	24.0 Hours	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	17.3 Hours	Geometric Coefficient of Variation 62.6
Part 1:GSK2879552 1.5 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	8.8 Hours	Geometric Coefficient of Variation 8.7
Part 1: GSK2879552 2.0 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	18.1 Hours	Geometric Coefficient of Variation 8.7
Part 1: GSK2879552 3.0 mg Daily	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	15.4 Hours	Geometric Coefficient of Variation 19.1
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	11.5 Hours	Geometric Coefficient of Variation 47.9
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	8.9 Hours	Geometric Coefficient of Variation 23.2
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 6, 3, 2, 5, 1	8.4 Hours	—

Secondary

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-infinity) following single (Day 1) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1

Population: Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	14.5 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	27.2 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	40.0 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 18.7
Part 1:GSK2879552 1.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	70.7 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 15
Part 1: GSK2879552 2.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	108.6 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 56.1
Part 1: GSK2879552 3.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	206.3 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 27.7
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	163.6 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 25.3
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	182.9 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 27.1
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552	180.9 Hour*Nanogram per milliliter	—

Secondary

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-t) following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	10.4 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 0.25 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	27.0 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	21.6 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	40.7 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	53.6 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 31.5
Part 1:GSK2879552 1.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	32.4 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 15.7
Part 1:GSK2879552 1.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	91.1 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 1.5 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	60.8 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 13.8
Part 1: GSK2879552 2.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	144.1 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 64.6
Part 1: GSK2879552 2.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	86.0 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 57.6
Part 1: GSK2879552 3.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	190.0 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 29.6
Part 1: GSK2879552 3.0 mg Daily	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	122.1 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 30.4
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	148.0 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 29.9
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	164.1 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 7.8
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0	184.4 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 40.4
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	155.2 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 29
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	129.1 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 26.2

Secondary

Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including AUC (0-tau) following repeat (Day 15) dose administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Day 15

Population: Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	27.3 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	40.3 Hour*Nanogram per milliliter	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	53.3 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 31.2
Part 1:GSK2879552 1.5 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	91.1 Hour*Nanogram per milliliter	—
Part 1: GSK2879552 2.0 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	143.8 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 64.2
Part 1: GSK2879552 3.0 mg Daily	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	141.9 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 32.4
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	164.7 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 8.2
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552	203.4 Hour*Nanogram per milliliter	Geometric Coefficient of Variation 37.2

Secondary

Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)

The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Estimates and standard error have been presented.

Time frame: Baseline and median of 7.286 weeks of drug exposure

Population: Pharmacokinetic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)	81.8512 Hour*Nanogram per milliliter	Standard Error 6.0391

Secondary

Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax

Time frame: Baseline and median of 7.286 weeks of drug exposure

Population: Pharmacokinetic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax	10.3948 Nanogram per milliliter	Standard Error 1.2666

Secondary

Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including Cmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	3.8 Nanogram per milliliter	—
Part 1:GSK2879552 0.25 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	3.4 Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	4.3 Nanogram per milliliter	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	2.9 Nanogram per milliliter	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	6.4 Nanogram per milliliter	Geometric Coefficient of Variation 17.3
Part 1:GSK2879552 1.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	6.9 Nanogram per milliliter	Geometric Coefficient of Variation 29.2
Part 1:GSK2879552 1.5 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	13.8 Nanogram per milliliter	—
Part 1:GSK2879552 1.5 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	9.3 Nanogram per milliliter	Geometric Coefficient of Variation 12.2
Part 1: GSK2879552 2.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	12.9 Nanogram per milliliter	Geometric Coefficient of Variation 36.6
Part 1: GSK2879552 2.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	15.7 Nanogram per milliliter	Geometric Coefficient of Variation 39.4
Part 1: GSK2879552 3.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	22.0 Nanogram per milliliter	Geometric Coefficient of Variation 42.9
Part 1: GSK2879552 3.0 mg Daily	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	15.2 Nanogram per milliliter	Geometric Coefficient of Variation 23.1
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	31.2 Nanogram per milliliter	Geometric Coefficient of Variation 26.8
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	24.4 Nanogram per milliliter	Geometric Coefficient of Variation 21.5
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	23.9 Nanogram per milliliter	Geometric Coefficient of Variation 20.8
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	28.1 Nanogram per milliliter	Geometric Coefficient of Variation 7.7
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	23.4 Nanogram per milliliter	Geometric Coefficient of Variation 68.8

Secondary

Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose

The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was characterized by linear and/or non-linear mixed effect models. Only dose cohorts with repeat daily dosing were included in the analysis of platelet as a pharmacodynamic effect. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. Estimates and standard error have been presented.

Time frame: Baseline and median of 7.286 weeks of drug exposure

Population: Pharmacokinetic Population

Arm	Measure	Value (MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose	1.7444 Milligrams	Standard Error 0.1436

Secondary

Part 1: Number of Participants Achieving Disease Control Rate at Week 16

The clinical activity of GSK2879552 given orally in participants with SCLC was evaluated by assessing disease control rate. Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate (CR+PR+SD) based on RECIST version 1.1 at Week 16. Disease control rate was defined as number of participants achieving CR, PR and SD per RECIST version 1.1. The number of participants achieving disease control rate have been presented.

Time frame: Week 16

Population: All Treated Population.

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	1 Participants
Part 1:GSK2879552 0.5 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	0 Participants
Part 1:GSK2879552 1.0 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	0 Participants
Part 1:GSK2879552 1.5 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	0 Participants
Part 1: GSK2879552 2.0 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	1 Participants
Part 1: GSK2879552 3.0 mg Daily	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	1 Participants
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	0 Participants
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Number of Participants Achieving Disease Control Rate at Week 16	0 Participants

Secondary

Part 1: Time Invariance Ratio Following Administration of GSK2879552

Time invariance was assessed to evaluate whether the pharmacokinetics remains unaltered after repeat dosing. The mixed effect model was fitted with day as a fixed effect and participant as a random effect for each treatment (dose) separately. AUC (0-tau) on Day 15 was compared to AUC (0-infinity) on Day 1 in order to assess time invariance for each dose. The ratio and 90 percent CI were calculated by back-transforming the difference between the LS means for the two days and associated 90 percent CI, for each dose. Only dose cohorts with repeat daily dosing were analyzed.

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population. Only those participants with data available at specific time point were analyzed.

Arm	Measure	Value (NUMBER)
Part 1:GSK2879552 0.25 mg Daily	Part 1: Time Invariance Ratio Following Administration of GSK2879552	1.332 Ratio of AUC
Part 1:GSK2879552 0.5 mg Daily	Part 1: Time Invariance Ratio Following Administration of GSK2879552	1.206 Ratio of AUC
Part 1:GSK2879552 1.0 mg Daily	Part 1: Time Invariance Ratio Following Administration of GSK2879552	0.688 Ratio of AUC

Secondary

Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552

Blood samples were collected from participants for pharmacokinetic analysis including Tmax following single (Day 1) and repeat dose (Day 15) administration of GSK2879552. Tmax is the time to reach Cmax, determined directly from the concentration-time data. Pharmacokinetic analysis of GSK2879552 in Part 1 was conducted by non-compartmental methods. NA represents data was not available. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1 and Day 15

Population: Pharmacokinetic Population

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Part 1:GSK2879552 0.25 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.5 Hours	—
Part 1:GSK2879552 0.25 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.0 Hours	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	1.5 Hours	—
Part 1:GSK2879552 0.5 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.5 Hours	—
Part 1:GSK2879552 1.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	0.9 Hours	Geometric Coefficient of Variation 65.1
Part 1:GSK2879552 1.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.5 Hours	Geometric Coefficient of Variation 2.8
Part 1:GSK2879552 1.5 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	0.5 Hours	—
Part 1:GSK2879552 1.5 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	1.3 Hours	Geometric Coefficient of Variation 110.4
Part 1: GSK2879552 2.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.1 Hours	Geometric Coefficient of Variation 88.6
Part 1: GSK2879552 2.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.8 Hours	Geometric Coefficient of Variation 108.5
Part 1: GSK2879552 3.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	1.6 Hours	Geometric Coefficient of Variation 42.5
Part 1: GSK2879552 3.0 mg Daily	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.5 Hours	Geometric Coefficient of Variation 86.3
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.8 Hours	Geometric Coefficient of Variation 85.8
Part 1: GSK2879552 3.0 mg 4 Days on/3 Days Off	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.4 Hours	Geometric Coefficient of Variation 52.1
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0	1.0 Hours	Geometric Coefficient of Variation 46.7
Part 1: GSK2879552 3.0 mg 4 Days on/10 Days Off	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	1.2 Hours	Geometric Coefficient of Variation 52.6
Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off	Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552	Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2	0.7 Hours	Geometric Coefficient of Variation 52.1

Secondary

Part 2: Clearance Following Administration of GSK2879552

Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including clearance. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Population: Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Secondary

Part 2: Duration of Response

Duration of response for participants is defined as the time from the first documented evidence of a PR or CR until the first documented sign of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)

The pharmacokinetic/pharmacodynamic relationship of GSK2879552 administered orally was planned to be characterized by linear and/or non-linear mixed effect models. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date. Percentage change from Baseline was defined as post-dose visit value minus Baseline value, divided by Baseline value and multiplied by 100. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Baseline and Up to 2 years

Population: Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Secondary

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax

Time frame: Baseline and up to 2 years

Population: Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Secondary

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose

Time frame: Baseline and up to 2 years

Population: Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Secondary

Part 2: Number of Participants With Abnormal Findings for ECG Parameters

Single measurements of 12-lead ECGs were planned to be obtained in a semi-recumbent or supine position after at least a 5 minutes rest using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With Abnormal Findings Undergoing Physical Examinations

The complete physical examination includes assessments of the head, eyes, ears, nose, throat, skin, thyroid, neurological, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. A brief physical examination includes assessments of the skin, lungs, cardiovascular system, and abdomen (liver and spleen). This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline

Blood samples were planned to be collected for evaluation of clinical chemistry parameters including potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, ALT, uric acid, glucose, GGT, albumin, sodium, calcium, alkaline phosphatase, and phosphorus inorganic. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Baseline and up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With Change in Hematology Toxicity Grade From Baseline

Blood samples were planned to be collected for the analysis of hematology parameters including hemoglobin, lymphocytes, total neutrophils, platelet count and white blood cell (WBC) count. Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Baseline and up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug

Vital sign measurement includes SBP, DBP, temperature, respiration rate and heart rate. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With DLTs

An event was considered a DLT if it occured within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event is unrelated to treatment: recurrent Grade 3 anemia after initial transfusion or Grade 3 anemia lasting \> 7 days in participants who are not transfused, Grade 4 neutropenia, Grade 3 neutropenia \> 7 days duration, febrile neutropenia as defined by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, Grade 3 thrombocytopenia requiring dose reduction, Grade 4 thrombocytopenia lasting \> 3 days or of any duration if associated with clinically significant bleeding, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 2 toxicity (at any time during treatment) and treatment delay of 14 days or greater due to unresolved drug-related toxicity. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With Dose Reduction or Delays

The number of participants who had any dose reduction or delay were planned to be analyzed. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants Withdrawn Due to Toxicities

Participants were planned to be monitored from start of the study till the development of toxicity in Part 2. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Number of Participants With SAEs and Non-SAEs

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Percentage of Participants Achieving CR and PR

Overall response rate is defined as percentage of participants achieving CR and PR per RECIST version 1.1. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Progression Free Survival (PFS)

PFS is defined as the interval between the first dose of study medication and the earliest date of disease progression or death due to any cause. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Up to 2 years

Population: All Treated Population. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Secondary

Part 2: Volume of Distribution Following Administration of GSK2879552

Blood samples were planned to be collected for population pharmacokinetic analysis of GSK2879552 including volume of distribution. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

Time frame: Pre-dose, 0.5, and 3 hours post-dose on Day 1; Pre-dose on Day 8; Pre-dose, 0.5 to 1 hour, and 4 to 6 hours on Day 15; Pre-dose at Day 22 and up to every 4 weeks until Week 48

Population: Pharmacokinetic Population. Data was not collected in Part2 as no participant was enrolled in Part2.

Source: ClinicalTrials.gov · Data processed: Mar 2, 2026

Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma

Conditions

Keywords

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Part 1: Number of Participants With Abnormal Findings for Electrocardiogram (ECG) Parameters

Part 1: Number of Participants With Abnormal Findings Undergoing Physical Examinations

Part 1: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline

Part 1: Number of Participants With Change in Hematology Toxicity Grade From Baseline

Part 1:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug

Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

Part 1: Number of Participants With Dose Reduction or Delays

Part 1: Number of Participants Withdrawn Due to Toxicities

Part 1: Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs

Part 2: Number of Participants Achieving Disease Control Rate at Week 16

Part 1: Accumulation Ratio Following Administration of GSK2879552

Part 1: Apparent Terminal Phase Elimination Rate Constant (Lambda z) Following Single and Repeat Dose Administration of GSK2879552

Part 1: Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of GSK2879552

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of GSK2879552

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) Following Single and Repeat Dose Administration of GSK2879552

Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552

Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)

Part 1: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax

Part 1: Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of GSK2879552

Part 1 :Median Effective Dose (ED50) of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose

Part 1: Number of Participants Achieving Disease Control Rate at Week 16

Part 1: Time Invariance Ratio Following Administration of GSK2879552

Part 1: Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of GSK2879552

Part 2: Clearance Following Administration of GSK2879552

Part 2: Duration of Response

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and AUC (0 to Infinity)

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Cmax

Part 2: ED50 of GSK2879552 With Respect to Platelet Nadir as Percent Change From Baseline and Dose

Part 2: Number of Participants With Abnormal Findings for ECG Parameters

Part 2: Number of Participants With Abnormal Findings Undergoing Physical Examinations

Part 2: Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline

Part 2: Number of Participants With Change in Hematology Toxicity Grade From Baseline

Part 2:Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug

Part 2: Number of Participants With DLTs

Part 2: Number of Participants With Dose Reduction or Delays

Part 2: Number of Participants Withdrawn Due to Toxicities

Part 2: Number of Participants With SAEs and Non-SAEs

Part 2: Percentage of Participants Achieving CR and PR

Part 2: Progression Free Survival (PFS)

Part 2: Volume of Distribution Following Administration of GSK2879552