Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Part 1: Number of Participants With Any Serious Adverse Event (SAE) and Non-serious Adverse Event (Non-SAE) |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
Up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Any SAE and Non-SAE |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
Up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Any SAE and Non-SAE |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward medical occurrence that, at any dose: resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly or birth defect or any other situation according to medical or scientific judgment was categorized as SAE. |
Up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs) |
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of >7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
28 days |
|
Primary |
Part 2A: Number of Participants With DLTs |
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of >7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
28 days |
|
Primary |
Part 2B: Number of Participants With DLTs |
An adverse event was considered as DLT if it was considered by the investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment, occurred within the first 28 days of the treatment, and met 1 of the following criteria: Hematologic: Febrile neutropenia, Grade4 neutropenia of >7days requiring Granulocyte colony-stimulating factor (G-CSF), Grade4 anemia of any duration, Grade4 thrombocytopenia of any duration or Grade3 thrombocytopenia with bleeding as described in National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4). Non-hematologic: Grade4 toxicity, Grade3 toxicity that cannot be controlled within 3days, Ocular toxicity of >=Grade3 or of Grade2 requiring systemic steroids. Any other event results in permanent discontinuation of treatment during the first 4 weeks of treatment or any other event which in the judgment of the investigator and GlaxoSmithKline medical monitor is considered to be a DLT. |
28 days |
|
Primary |
Part 1: Number of Participants With Any Adverse Event Leading to Withdrawal (AELD) From the Study |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
Up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
Up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Any Adverse Event Leading to Withdrawal From the Study |
An adverse event is any untoward medical occurrence in a participant or clinical investigation participant temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with any adverse event leading to withdrawal from the study is presented. |
Up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Dose Reductions or Delay |
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
Up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Dose Reductions or Delay |
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
Up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Dose Reductions or Delay |
Number of participants who had any dose reduction or dose delay (GSK3174998) due to any reason have been presented. |
Up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Any Grade Change From Baseline in Hematology Parameters |
Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), leukocyte count (leuko.), lymphocyte count (Lymph.), neutrophil count (Neutro.) and platelet count (PC). The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Any Grade Change From Baseline in Hematology Parameters |
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Any Grade Change From Baseline in Hematology Parameters |
Blood samples were collected for the analysis of following hematology parameters: Hb, leuko., Lymph., Neutro. and PC. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters |
Blood samples were collected for the analysis of following liver function laboratory parameters: alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters |
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Any Grade Change From Baseline in Liver Function Laboratory Parameters |
Blood samples were collected for the analysis of following liver function laboratory parameters: ALT, ALP, AST and bilirubin. The laboratory parameters were graded according to NCI-CTCAE version 4. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline was defined as the most recent, non-missing value from a central laboratory prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Any Grade Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) |
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Any Grade Change From Baseline in SBP and DBP |
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Any Grade Change From Baseline in SBP and DBP |
SBP and DBP were graded using NCI-CTCAE version 4. For SBP: Grade 0: <120 mmHg; Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Any grade increase is defined as an increase in NCI-CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with any grade increase have been presented. |
Baseline (Day 1) and up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Worst Case Change From Baseline in Heart Rate (HR) |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 beats per minute [bpm]', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 39 weeks |
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Primary |
Part 2A: Number of Participants With Worst Case Change From Baseline in HR |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Worst Case Change From Baseline in HR |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in heart rate is presented. Data was categorized as: heart rate 'decrease to low', 'increase to high' and 'change to normal or no change'; where low HR: <60 bpm', normal HR: 60 to 100 bpm and high HR: >100 bpm. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Worst Case Change From Baseline in Body Temperature |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Worst Case Change From Baseline in Body Temperature |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 105 weeks |
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Primary |
Part 2B: Number of Participants With Worst Case Change From Baseline in Body Temperature |
Baseline was defined as the most recent, non-missing value prior to or on the first study treatment dose date (Day 1). Change from Baseline was defined as post Baseline value minus Baseline value. Number of participants with worst case change from Baseline in body temperature is presented. Data was categorized as: 'decrease to low', 'increase to high' and 'change to normal or no change'; where low body temperature: <=35 degrees Celsius, normal body temperature: 35 to 38 degrees Celsius and high body temperature: >=38 degrees Celsius. If values were unchanged (example: increase to >=38 degrees Celsius to increase to >=38 degrees Celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both 'decreased to low' and 'increased to high' during post Baseline, so the percentages might not add to 100%. |
Baseline (Day 1) and up to maximum 33 weeks |
|
Primary |
Part 1: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant Electrocardiogram (ECG) Findings |
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
Up to maximum 39 weeks |
|
Primary |
Part 2A: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings |
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
Up to maximum 105 weeks |
|
Primary |
Part 2B: Number of Participants With Worst Case Post-Baseline Abnormal Clinically Significant ECG Findings |
A 12-lead ECG was obtained after the participant had rested at least 10 minutes in a semi-recumbent or supine position during the study using ECG machine. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Number of participants with worst case post Baseline abnormal clinical significant ECG findings are presented. |
Up to maximum 33 weeks |
|
Secondary |
Part 1: Objective Response Rate (ORR) |
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or a partial response (PR) as the Best Overall Response (BOR), as assessed by the investigator per Response Evaluation Criteria In Solid Tumors (RECIST) Version (v) 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30 percent (%) decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
Up to maximum 39 weeks |
|
Secondary |
Part 2A: Objective Response Rate (ORR) |
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
Up to maximum 105 weeks |
|
Secondary |
Part 2B: Objective Response Rate (ORR) |
ORR is defined as the percentage of participants achieving a confirmed CR or PR as the BOR, as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. |
Up to maximum 33 weeks |
|
Secondary |
Part 1: Disease Control Rate (DCR) |
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus stable disease (SD) >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
Up to maximum 39 weeks |
|
Secondary |
Part 2A: Disease Control Rate (DCR) |
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
Up to maximum 105 weeks |
|
Secondary |
Part 2B: Disease Control Rate (DCR) |
DCR is defined as the percentage of participants with a confirmed CR or PR at any time, plus SD >=12 weeks as assessed by the investigator per RECIST v 1.1 criteria. CR: Disappearance of all lesions in two consecutive observations not less than 4 weeks apart. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter. PR: >=30% decrease in tumor burden compared with Baseline in two observations at least 4 weeks apart. SD: 30% decrease in tumor burden compared with Baseline cannot be established nor 20% increase compared with nadir. |
Up to maximum 33 weeks |
|
Secondary |
Part 1: Plasma Concentrations of GSK3174998 at Indicated Time Points |
Blood samples for pharmacokinetic (PK) analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion |
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Secondary |
Part 2A: Plasma Concentrations of GSK3174998 at Indicated Time Points |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion |
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Secondary |
Part 2B: Plasma Concentrations of GSK3174998 at Indicated Time Points |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion (EOI); anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion |
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Secondary |
Part 1: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 2A: AUC(0-tau) of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 2B: AUC(0-tau) of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Day 43: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 1: Maximum Observed Concentration (Cmax) and Minimum Observed Concentration (Cmin) of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 2A: Cmax and Cmin of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 2B: Cmax and Cmin of GSK3174998 |
Blood samples for PK analysis of GSK3174998 were collected on Days 1, 22: Pre-dose and within 30 minutes, 4 hour, 24 hour after end of GSK3174998 infusion; anytime on Days 8, 15, 29 and 36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion. Each dosing cycle was of 21 days. PK parameters of GSK3174998 were calculated using non-compartmental methods. |
Days 1, 22: Pre-dose and within 30 minutes, 4 hours, 24 hours after end of GSK3174998 infusion; anytime on Days 8,15,29,36; Days 43, 64, 85, 106: Pre-dose and within 30 minutes after end of GSK3174998 infusion (each dosing cycle was of 21 days) |
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Secondary |
Part 2A: Plasma Concentrations of Pembrolizumab at Indicated Time Points |
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion (EOPI); anytime on Days 8,15; Pre-dose on Days 22, 64, 106. |
Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 |
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Secondary |
Part 2B: Plasma Concentrations of Pembrolizumab at Indicated Time Points |
Blood samples for PK analysis of pembrolizumab were collected on Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22, 64, 106. |
Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22, 64, 106 |
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Secondary |
Part 2A: AUC(0-tau) of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) |
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Secondary |
Part 2B: AUC(0-tau) of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) |
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Secondary |
Part 2A: Cmax of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) |
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Secondary |
Part 2B: Cmax of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15, Pre-dose on Day 22 (each dosing cycle was of 21 days) |
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Secondary |
Part 2A: Cmin of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) |
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Secondary |
Part 2B: Cmin of Pembrolizumab |
Blood samples for PK analysis of pembrolizumab were collected on Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after EOPI; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days). PK parameters of pembrolizumab were calculated using non-compartmental methods. |
Cycle 1 Day 1: Pre-dose and within 30 minutes, 24 hours after end of pembrolizumab infusion; anytime on Days 8,15; Pre-dose on Days 22; Cycle 3 (Day 64), Cycle 5 (Day 106) (each dosing cycle was of 21 days) |
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Secondary |
Part 1: Number of Participants With Positive Antidrug Antibodies (ADAs) Against GSK3174998 |
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point determined during assay validation. Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
Up to maximum 39 weeks |
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Secondary |
Part 2A: Number of Participants With Positive ADAs Against GSK3174998 |
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
Up to maximum 105 weeks |
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Secondary |
Part 2B: Number of Participants With Positive ADAs Against GSK3174998 |
Serum samples were collected for the determination of anti-GSK3174998 antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a GSK3174998 bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with GSK3174998 that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-GSK3174998 antibodies results at any visit during the study have been presented. |
Up to maximum 33 weeks |
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Secondary |
Part 2A: Number of Participants With Positive ADAs Against Pembrolizumab |
Serum samples were collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. The presence of treatment emergent ADA was determined using a pembrolizumab bridging style ADA assay with a bio-analytically determined cut-point (determined during assay validation). Samples taken after dosing with pembrolizumab that had a value at or above the cut-point was considered treatment-emergent ADA-positive. These ADA positive samples were further evaluated in a confirmatory assay, and confirmed positive samples were further characterized by assessment of titer. Number of participants with confirmed positive anti-pembrolizumab antibodies results at any visit during the study have been presented. |
Up to maximum 105 weeks |
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Secondary |
Part 2B: Number of Participants With Positive ADAs Against Pembrolizumab |
Serum samples were planned to be collected for the determination of anti-pembrolizumab antibodies using binding ADA assay method using a tiered testing schema: screening, confirmation and titration steps. |
Up to maximum 33 weeks |
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