Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Carcinoma

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma, Small Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

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).The dose escalation will complete when RP2D is determined. The RP2D will be the MTD or a lower dose that provides adequate PK exposure and biologic activity with superior tolerability.

Once the RP2D has been determined, an expansion cohort of up to 30 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D

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

GSK2879552

GSK Clinical Trials

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.

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

IPD for this study will be made available via the Clinical Study Data Request site.

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.

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.

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

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.

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).

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.

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.

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.

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.

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.

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).

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.

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.

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).

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).

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).

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).

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

GlaxoSmithKline

SAEs and non-SAEs were collected in Part 1 from All Treated Population which included all participants who received at least one dose of study treatment. Data were not collected in Part 2 as no participant was enrolled in Part 2.

Participants received GSK2879552 with a starting dose of 0.25 mg once daily, administered orally with approximately 200 milliliter of water for 28 days.

Part 1:GSK2879552 0.25 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.

Part 1:GSK2879552 0.5 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.

Part 1:GSK2879552 1.0 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.

Part 1:GSK2879552 1.5 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.

Part 1: GSK2879552 2.0 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.

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 4 days during the treatment period following buffer period of 3 days.

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 10 days.

Part 1: GSK2879552 3.0 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.

Part 1: GSK2879552 4.0 mg 4 Days on/10 Days Off

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.

Part 2:GSK2879552 0.25 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.

Part 2:GSK2879552 0.5 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.

Part 2:GSK2879552 1.0 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.

Part 2:GSK2879552 1.5 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.

Part 2: GSK2879552 2.0 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.

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 4 days during the treatment period following buffer period of 3 days.

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 10 days.

Part 2: GSK2879552 3.0 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.

Part 2: GSK2879552 4.0 mg 4 Days on/10 Days Off

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Data was collected only in Part 1 and no participants were enrolled in Part 2.

GSK Response Center

Any non-SAE

Any SAE

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

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

Albumin;n=1,1,5,3,5,3,2,5,2

Alkaline Phosphatase;n=1,1,5,3,5,3,2,5,2

ALT;n=1,1,5,3,5,3,2,5,2

AST;n=1,1,5,3,5,3,2,5,2

Total Bilirubin;n=1,1,5,3,5,3,2,5,2

Calcium;n=1,1,5,3,5,3,2,5,2

Calcium (hypercalcemia);n=1,1,5,3,5,3,2,5,2

Calcium (hypocalcemia);n=1,1,5,3,5,3,2,5,2

Creatinine;n=1,1,5,3,5,3,2,5,2

GGT;n=1,1,5,3,5,3,2,5,2

Glucose;n=1,1,5,3,6,3,2,5,2

Glucose (hyperglycemia);n=1,1,5,3,6,3,2,5,2

Glucose (hypoglycemia);n=1,1,5,3,6,3,2,5,2

Potassium;n=1,1,5,2,5,3,2,5,2

Potassium (hyperkalemia);n=1,1,5,2,5,3,2,5,2

Potassium (hypokalemia);n=1,1,5,2,5,3,2,5,2

Sodium;n=1,1,5,3,5,3,2,5,2

Sodium (hypernatremia);n=1,1,5,3,5,3,2,5,2

Sodium (hyponatremia);n=1,1,5,3,5,3,2,5,2

Phosphorus, inorganic;n=1,1,5,3,5,3,2,5,2

Uric acid;n=0,0,1,0,0,1,0,0,1

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

Hemoglobin

Hemoglobin (Increased)

Hemoglobin (Anemia)

Lymphocytes

Lymphocytes (Increased)

Lymphocytes (Decreased)

Total Neutrophils

Platelet count

WBC count

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

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

Abnormal - not clinically significant

Abnormal - clinically significant

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

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

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

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

Day 1; n=1, 1, 5, 3, 7, 3, 2, 5, 2

Day 15; n=1, 1, 5, 1, 5, 3,2, 5,0

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

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

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 Over the Dosing Interval (AUC [0-tau]) Following Repeat Dose Administration of GSK2879552

Day 15; n=1, 1, 5, 1, 5, 3, 2, 5, 0

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

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

Day 1; n= 1, 1, 5, 3, 6, 3, 2, 5, 1

Day 15; n=0,0,0,0, 0,0,0,0,0

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

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

Part 1: Accumulation Ratio Following Administration of GSK2879552

Part 1: Time Invariance Ratio Following Administration of GSK2879552

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

Participants received repeat daily dosing with GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were escalated to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.

Part 1: Participants With Repeat Daily Dosing

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

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

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

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

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 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 Abnormal Findings for ECG Parameters

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

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

Part 2: Clearance Following Administration of GSK2879552

Part 2: Volume of Distribution Following Administration of GSK2879552

Participants with repeat daily dosing were planned to receive GSK2879552 with a starting dose of 0.25 mg once daily for 28 days. The doses were planned to escalate to receive either 0.25 mg or 0.5 or 1 mg or 1.5 or 2 mg or 3 mg daily for 28 days.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Investigation of GSK2879552 in Subjects With Relapsed/Refractory Small Cell Lung Carcinoma	NCT02034123	Carcinoma, Smal...	GSK2879552	18 Years -	GlaxoSmithKline
First Time in Humans (FTIH) Study of GSK3368715 in Participants With Solid Tumors and Diffuse Large B-cell Lymphoma (DLBCL)	NCT03666988	Neoplasms	GSK3368715 GSK3368715	18 Years -	GlaxoSmithKline

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