Best Overall Response (BOR) Rate-Part 1
Best overall response is defined as the best unconfirmed response (Complete Response [CR] > Partial Response [PR] > Stable Disease [SD] [or non-CR/non-PD] > Progressive Disease [PD] > Not Evaluable [NE]) from treatment start date until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST version 1.1 Criteria. The BOR rate is defined as the percentage of participants with each best unconfirmed response category. Participants with unknown or missing responses were treated as non-responders, i.e., these participants were included in the denominator when calculating percentages of response.
Best Overall Response (BOR) Rate-Part 2
Best overall response is defined as the best unconfirmed response (CR > PR > SD [or non-CR/non-PD] > PD] > NE) from treatment start date until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST 1.1 Criteria. The BOR rate is defined as the percentage of participants with each best unconfirmed response category. Participants with unknown or missing responses were treated as non-responders, i.e., these participants were included in the denominator when calculating percentages of response.
Progression-free Survival (PFS)-Part 3
PFS is defined as time from the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. If the participant received subsequent anti-cancer therapy prior to the date of documented events, PFS was to be censored at the last adequate assessment (e.g., assessment where visit level response is confirmed response, partial response or stable disease) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of event, PFS was to be censored at the date of the last adequate assessment.
Progression-Free Survival (PFS) -Part 4
PFS is defined as time from the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. If the participant received subsequent anti-cancer therapy prior to the date of documented events, PFS was to be censored at the last adequate assessment (e.g., assessment where visit level response is confirmed response, partial response or stable disease) prior to the initiation of therapy. Otherwise, if the participant did not have a documented date of event, PFS was to be censored at the date of the last adequate assessment.
Overall Survival -Part 3
Overall survival is defined as time from the date of first dose to the date of death due to any cause. If a participant does not have a documented date of death, time of death is censored at the date of last contact.
Overall Survival -Part 4
Overall survival is defined as time from the date of first dose to the date of death due to any cause. If a participant does not have a documented date of death, time of death is censored at the date of last contact.
Number of Participants With Non-serious AEs and SAEs-Part 3
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations.
Number of Participants With Non-serious AEs and SAEs-Part 4
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. SAE is defined as any untoward medical occurrence that, at any dose which results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or other situations.
Number of Participants With AEs by Severity Grades-Part 3
All adverse events were planned to be analyzed using NCI-CTCAE Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition.
Number of Participants With AEs by Severity Grades-Part 4
All adverse events were planned to be analyzed using NCI-CTCAE Version 5.0. Graded from Grade 1: mild asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated, Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL, Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL, Grade 4: Life-threatening consequences; urgent intervention indicated, Grade 5: death related AE. Higher grade indicates more severe condition.
Area Under the Plasma Drug Concentration Versus Time Curve (AUC[0-t]) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of AUC(0-t) following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
AUC (0-t) Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095 on Day 1 and was to be calculated by standard non-compartmental analysis.
Area Under the Concentration-time Curve Over the Dosing Interval (AUC [0-tau]) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
AUC (0-tau) Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following single dose of GSK3145095.
Maximum Observed Plasma Drug Concentration (Cmax) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of Cmax following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
Cmax Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095 on Day 1.
Minimum Observed Plasma Drug Concentration (Cmin) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of Cmin following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
Cmin Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of Cmin following single dose of GSK3145095 on Day 1.
Time to Maximum Observed Plasma Drug Concentration (Tmax) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of tmax following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
Tmax Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of tmax following single dose of GSK3145095 on Day 1.
Clearance (CL/F) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of CL/F following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
CL/F Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of CL/F following single dose of GSK3145095 on Day 1.
Volume of Distribution (Vz/F) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of Vz/F following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
Vz/F Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of V/F following single dose of GSK3145095 on Day 1.
Terminal Half-life (t1/2) Following Single Dose of GSK3145095 on Day 1-Part 1
Blood samples were collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095 on Day 1 and was calculated by standard non-compartmental analysis.
T1/2 Following Single Dose of GSK3145095 on Day 1-Part 2
Blood samples were to be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095 on Day 1.
AUC (0-t) Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.
AUC (0-t) Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095 on Day 15.
AUC (0-tau) Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.
AUC (0-tau) Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of GSK3145095 on Day 15.
Cmax Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095 on Day 15 and was calculated by standard non-compartmental analysis.
Cmax Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095 on Day 15.
Cmin Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095 on day 15 and was calculated by standard non-compartmental analysis.
Cmin Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of Cmin following repeat dose of GSK3145095 on Day 15.
Tmax Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095 and was calculated by standard non-compartmental analysis.
Tmax Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095 on Day 15.
CL/F Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095 on Day 15. For accurate estimation of CL/F following repeated administration, it is imperative that steady state has been achieved. As the attainment of steady state could not be confirmed with certainty, CL/F was not computed following repeated dose.
CL/F Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of CL/F following repeat dose of GSK3145095 on Day 15.
Vz/F Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of Vz/F following repeat dose of GSK3145095 on Day 15. As t1/2 following repeated administration could not be computed, Vz/F whose estimation is dependent upon the t1/2 could not be estimated as well.
Vz/F Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of V/F following repeat dose of GSK3145095 on Day 15.
T1/2 Following Repeat Dose of GSK3145095 on Day 15-Part 1
Blood samples were collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095 on Day 15. t1/2 following repeated administration was not computed because duration of observation (12 hours from the morning dose) was too short (less than 2 times the average half-life observed after the first dose) for its accurate estimation.
T1/2 Following Repeat Dose of GSK3145095 on Day 15-Part 2
Blood samples were to be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095 on Day 15.
Dose Proportionality of GSK3145095 for Dose Levels 100 mg (50 mg BID) to 1600 mg (800 mg BID) Using AUC (0-t) Following Single Dose-Part 1
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality. As only one dose level (100 mg) was tested prior to termination of the study and multiple dose levels are required to investigate dose proportionality, hence dose proportionality could not be analyzed.
Dose Proportionality of GSK3145095 for Dose Levels 100 mg (50 mg BID) to 1600 mg (800 mg) BID Using Cmax Following Single Dose-Part 1
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality. As only one dose level (100 mg) was tested prior to termination of the study and multiple dose levels are required to investigate dose proportionality, hence dose proportionality could not be analyzed.
Dose Proportionality of GSK3145095 for Dose Levels 100 mg (50 mg BID) to 1600 mg (800 mg BID) Using AUC (0-tau) Following Repeat Dose-Part 1
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality. As only one dose level (100 mg) was tested prior to termination of the study and multiple dose levels are required to investigate dose proportionality, hence dose proportionality could not be analyzed.
Dose Proportionality of GSK3145095 for Dose Levels 100 mg (50 mg BID) to 1600 mg (800 mg BID) Using Cmax Following Repeat Dose-Part 1
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality. As only one dose level (100 mg) was tested prior to termination of the study and multiple dose levels are required to investigate dose proportionality, hence dose proportionality could not be analyzed.
Dose Proportionality of GSK3145095 Using AUC (0-t) Following Single Dose-Part 2
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality of GSK3145095 Using Cmax Following Single Dose-Part 2
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality of GSK3145095 Using AUC (0-tau) Following Repeat Dose-Part 2
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality Using Cmax Following Repeat Dose of GSK3145095-Part 2
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Accumulation Ratio Following Repeat Dose of GSK3145095 on Day 15-Part 1
Accumulation ratio was calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Accumulation Ratio Following Repeat Dose of GSK3145095 on Day 15-Part 2
Accumulation ratio was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Time Invariance of GSK3145095-Part 1
Blood samples were collected at indicated time points for analysis of time invariance. Time invariance was calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Time Invariance of GSK3145095-Part 2
Blood samples were to be collected at indicated time points for analysis of time invariance. Time invariance were to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Plasma Concentration of Pembrolizumab -Part 2
Blood samples were to be collected at indicated time points for the determination of plasma concentration of pembrolizumab.
Cmax of Pembrolizumab-Part 2
Blood samples were to be collected at indicated time points for the determination of Cmax of pembrolizumab.
AUC (0-tau) of Pembrolizumab-Part 2
Blood samples were to be collected at indicated time points for the determination of AUC (0-tau) of pembrolizumab.
Cmin of Pembrolizumab-Part 2
Blood samples were to be collected at indicated time points for the determination of Cmin of pembrolizumab.
AUC (0-t) Following Single Dose of GSK3145095 on Day 1-Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of GSK3145095 on Day 1.
Cmax Following Single Dose of GSK3145095 on Day 1-Part 3
Blood samples were to be collected at the indicated time points for the determination of Cmax following single dose of GSK3145095 on Day 1.
Tmax Following Single Dose of GSK3145095 on Day 1-Part 3
Blood samples were to be collected at the indicated time points for the determination of tmax following single dose of GSK3145095 on Day 1.
T1/2 Following Single Dose of GSK3145095 on Day 1-Part 3
Blood samples were to be collected at the indicated time points for the determination of t1/2 following single dose of GSK3145095 on Day 1.
AUC (0-t) Following Repeat Dose of GSK3145095 on Day 15-Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of GSK3145095 on Day 15.
Cmax Following Repeat Dose of GSK3145095 on Day 15-Part 3
Blood samples were to be collected at the indicated time points for the determination of Cmax following repeat dose of GSK3145095 on Day 15.
Tmax Following Repeat Dose of GSK3145095 on Day 15-Part 3
Blood samples were to be collected at the indicated time points for the determination of tmax following repeat dose of GSK3145095 on Day 15.
T1/2 Following Repeat Dose of GSK3145095 on Day 15-Part 3
Blood samples were to be collected at the indicated time points for the determination of t1/2 following repeat dose of GSK3145095 on Day 15.
AUC (0-t) Following Single Dose of Pembrolizumab-Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following single dose of pembrolizumab.
AUC (0-tau) Following Single Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following single dose of pembrolizumab.
Cmax Following Single Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of Cmax following single dose of pembrolizumab.
Tmax Following Single Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of tmax following single dose of pembrolizumab.
T1/2 Following Single Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of t1/2 following single dose of pembrolizumab.
AUC (0-t) Following Repeat Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-t) following repeat dose of pembrolizumab.
AUC (0-tau) Following Repeat Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of AUC (0-tau) following repeat dose of pembrolizumab.
Cmax Following Repeat Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of Cmax following repeat dose of pembrolizumab.
Tmax Following Repeat Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of tmax following repeat dose of pembrolizumab.
T1/2 Following Repeat Dose of Pembrolizumab -Part 3
Blood samples were to be collected at the indicated time points for the determination of t1/2 following repeat dose of pembrolizumab.
Dose Proportionality of GSK3145095 Using AUC (0-t) Following Single Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality of GSK3145095 Using Cmax Following Single Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality of GSK3145095 Using AUC (0-tau) Following Repeat Dose of GSK3145095-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality of GSK3145095 Using Cmax Following Repeat Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Accumulation Ratio Following Repeat Dose of GSK3145095-Part 3
Accumulation ratio was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for GSK3145095.
Time Invariance Following Repeat Dose of GSK3145095-Part 3
Blood samples were to be collected at indicated time points for analysis of time invariance. Time invariance was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3145095.
Dose Proportionality for Pembrolizumab Using AUC (0-t) Following Single Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality for Pembrolizumab Using Cmax Following Single Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality for Pembrolizumab Using AUC (0-tau) Following Repeat Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Dose Proportionality for Pembrolizumab Using Cmax Following Repeat Dose-Part 3
Dose proportionality was to be evaluated for GSK3145095 using a fixed effects power model. Estimated slope was to be presented to express dose proportionality.
Accumulation Ratio Following Repeat Dose of Pembrolizumab-Part 3
Accumulation ratio was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-tau) at Day 1 for pembrolizumab.
Time Invariance Following Repeat Dose of Pembrolizumab-Part 3
Blood samples were to be collected at indicated timepoints for analysis of time invariance. Time invariance was to be calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for pembrolizumab.