This first time in human (FTIH) open-label, dose escalation study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK3326595 in participants with advanced or recurrent solid tumors, as well as clinical activity in participants with a subset of solid tumors and non-Hodgkin's lymphoma (NHL).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
297
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
Pembrolizumab will be administered.
GSK Investigational Site
Denver, Colorado, United States
GSK Investigational Site
Miami, Florida, United States
GSK Investigational Site
New York, New York, United States
Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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 resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the Medical Dictionary for Regulatory Affairs (MedDRA dictionary).
Time frame: Up to 30 months
Part 1: Number of Participants Withdrawn Due to AEs
The data for number of participants withdrawn due to AEs have been presented.
Time frame: Up to 30 months
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
DLT is considered to be clinically relevant AE by investigator if it met at least one of the criteria: Grade(G)3 neutropenia for \>=5 days/G4 neutropenia of any duration, G3 or greater febrile neutropenia, G4 or greater anemia of any duration and thrombocytopenia, or G3 thrombocytopenia with bleeding, Alanine aminotransferase (ALT) \>3x upper limit of normal (ULN)+bilirubin, \>=2xULN or ALT between 3-5 X ULN with bilirubin \< 2Xuln but with hepatitis symptoms/rash, G3 nausea/vomiting/diarrhea that does not improve within 72 hour, G4 or greater nausea/vomiting/diarrhea, G3 or greater hypertension, G3 or greater clinically significant non-hematologic toxicity per National Cancer Institute -- Common Terminology Criteria for Adverse Events (NCICTCAE), Inability to receive at least 80% of scheduled doses in the DLT observation period due to toxicity, G2 or higher toxicity that occurs beyond 21 days which in the judgment of the investigator and GSK Medical Monitor was considered to be a DLT.
Time frame: Up to 21 days
Part 1: Number of Participants With Dose Modifications of GSK3326595
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GSK Investigational Site
Nashville, Tennessee, United States
GSK Investigational Site
Dallas, Texas, United States
GSK Investigational Site
San Antonio, Texas, United States
GSK Investigational Site
Edmonton, Alberta, Canada
GSK Investigational Site
Ottawa, Ontario, Canada
GSK Investigational Site
Toronto, Ontario, Canada
GSK Investigational Site
Bordeaux, France
...and 5 more locations
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Time frame: Up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for evaluation of hematology parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Blood samples were collected for evaluation of coagulation parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v4.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Urine samples were collected for evaluation of urinalysis parameters. The summaries of worst-case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with no change or change to negative and change to positive have been presented.
Time frame: Baseline (Day 1) and up to 30 months
Part 1: Changes From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected from participants to assess urine pH levels.
Time frame: Baseline (Day 1) and up to week 132
Part 1: Changes From Baseline in Urine Specific Gravity
Urine samples were collected from participants to assess urine specific gravity.
Time frame: Baseline (Day 1) and up to week 132
Part 1: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs
The abnormal vital sign ranges are: Heart Rate:- Low (\<60 beats per minute (bpm)), Normal (\>=60 bpm to \<=100 bpm), High (\>100 bpm); Temperature:- Low (\<=35 degree Celsius (°C)), Normal (\>35 °C and \<38 °C), High (\>=38 °C); Systolic Blood Pressure:- Low (\<90 millimeter of mercury (mmHg)), Normal (\>=90 mmHg to \<120 mmHg), High (\>=120 mmHg); Diastolic Blood Pressure:- Low (\<60 mmHg), Normal (\>=60 mmHg to \<80 mmHg), High (\>=80 mmHg). Participants were counted in the worst-case category and their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 30 months
Part 3: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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 resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or was a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or is associated with liver injury and impaired liver function. SAEs are subset of AEs. A summary of number of participants with any AEs and SAEs is presented. AEs were coded using the MedDRA dictionary.
Time frame: Up to 10 months
Part 3: Number of Participants Withdrawn Due to AEs
The data for number of participants withdrawn due to AEs have been presented.
Time frame: Up to 10 months
Part 3: Number of Participants With Dose Modifications of GSK3326595 and Pembrolizumab
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 and pembrolizumab have been presented.
Time frame: Up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented.
Time frame: Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for evaluation of hematology parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with decreases to low, changes to normal or no changes from Baseline, and increases to high values have been presented.
Time frame: Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Blood samples were collected for evaluation of coagulation parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented.
Time frame: Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Urine samples were collected for evaluation of urinalysis parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with no change or change to negative and change to positive values have been presented.
Time frame: Baseline (Day 1) and up to 10 months
Part 3: Changes From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected from participants to assess urine pH levels.
Time frame: Baseline (Day 1) and up to Week 42
Part 3: Changes From Baseline in Urine Specific Gravity
Urine samples were collected from participants to assess urine specific gravity.
Time frame: Baseline (Day 1) and up to Week 42
Part 3: Number of Participants With Maximum Worst-case Increase Post-baseline Relative to Baseline in Vital Signs
The abnormal vital sign ranges are: Heart Rate:- Low \[\<60 bpm\], Normal (\>=60 bpm to \<=100 bpm), High (\>100 bpm); Temperature:- Low (\<=35 C), Normal (\>35 C and \<38 C), High (\>=38 C); Systolic Blood Pressure:- Low (\<90 mmHg), Normal (\>=90 mmHg to \<120 mmHg), High (\>=120 mmHg); Diastolic Blood Pressure:- Low (\<60 mmHg), Normal (\>=60 mmHg to \<80 mmHg), High (\>=80 mmHg). Participants were counted in the maximum worst case increase category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 10 months
Part 2: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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 resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involved medical or scientific judgment or was associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the MedDRA dictionary.
Time frame: Up to 42 months
Part 2: Number of Participants Withdrawn Due to AEs
The data for number of participants withdrawn due to AEs have been presented.
Time frame: Up to 42 months
Part 2: Number of Participants With Dose Modifications of GSK3326595
The number of participants who had any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Time frame: Up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for evaluation of hematology parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high values' have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Blood samples were collected for evaluation of coagulation parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Urine samples were collected for evaluation of urinalysis parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented.
Time frame: Baseline (Day 1) and up to 42 months
Part 2: Changes From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected from participants to assess urine pH levels.
Time frame: Baseline (Day 1) and up to week 184
Part 2: Changes From Baseline in Urine Specific Gravity
Urine samples were collected from participants to assess urine specific gravity.
Time frame: Baseline (Day 1) and up to week 184
Part 2: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs
The abnormal vital sign ranges are: Heart Rate:- Low (\<60 beats per minute (bpm)), Normal (\>=60 bpm to \<=100 bpm), High (\>100 bpm); Temperature:- Low (\<=35 degree Celsius (C)), Normal (\>35 C and \<38 C), High (\>=38 C); Systolic Blood Pressure:- Low (\<90 millimeter of mercury (mmHg)), Normal (\>=90 mmHg to \<120 mmHg), High (\>=120 mmHg); Diastolic Blood Pressure:- Low (\<60 mmHg), Normal (\>=60 mmHg to \<80 mmHg), High (\>=80 mmHg). Participants were counted in the worst-case category and their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to 42 months
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours (h) post-dose; pre-dose on day 8; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose on day 15
Part 3: Maximum Observed Plasma Concentration (Cmax) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Area Under the Plasma Concentration-time Curve (AUC) Extrapolated From Time Zero to Infinity (AUC[0-inf]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Part 3: Area Under the Plasma Concentration-time Curve (AUC) Extrapolated From Time Zero to Infinity (AUC[0-inf]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: AUC From Time Zero to the Last Quantifiable Concentration After Dosing (AUC[0-t]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose; pre-dose on day 8; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose on day 15
Part 3: AUC From Time Zero to the Last Quantifiable Concentration After Dosing (AUC[0-t]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose; pre-dose on day 8; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose on day 15
Part 3: AUC Over the Dosing Interval Tau (AUC[0-tau]) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Terminal Phase Half-life (t1/2) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 h post-dose; pre-dose on day 8; pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 h post-dose on day 15
Part 3: Terminal Phase Half-life (t1/2) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Oral Clearance (CL/F) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 3: Oral Clearance (CL/F) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Accumulation Ratio (AR) of GSK3326595
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose on Day 1 and Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose on Day 15
Part 3: Accumulation Ratio (AR) of GSK3326595
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Time Invariance (TI) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods. Time invariance was calculated as AUC(0-tau) at Day 15 divided by AUC(0-infinity) at Day 1 for GSK3326595.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose on Day 1 and Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose on Day 15
Part 3: Time Invariance (TI) of GSK3326595
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595.
Time frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Part 1: Overall Response Rate (ORR) Based on RECIST 1.1
ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) per RECIST version 1.1. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 mm.
Time frame: Up to 30 months
Part 2: Overall Response Rate (ORR) (Non-glioblastoma Multiforme [GBM] Cohorts)
Overall response rate (ORR) was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response (CR) was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm).
Time frame: Up to 42 months
Part 2: Six-month Progression Free Survival (PFS) Rate (GBM Cohort)
Six-month progression free survival (PFS) rate was defined as the percentage of participants free from radiographic progression per Response Assessment in Neuro-Oncology (RANO) criteria, or death due to any cause, for six months after starting GSK3326595. The RANO criteria were used to ascertain response (Wen, 2010).
Time frame: At month 6
Part 2: Duration of Response (DOR) (ACC Tablet Cohort)
Duration of response (DOR) was defined as time from first evidence of response (CR or PR per RECIST 1.1) to earlier date of disease progression or death due to any cause, as determined by Investigator assessment.
Time frame: Up to 42 months
Part 3: ORR Based on Immune-based RECIST (iRECIST) Criteria
ORR was defined as the percentage of participants with irCR or irPR per irRECIST. irCR is defined as disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeters (mm). irPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
Time frame: Up to 10 months
Part 2: ORR (GBM Cohort) Based on Response Assessment Neuro-Oncology (RANO) Working Group Criteria
ORR was defined as the percentage of participants with a CR or PR, confirmed no less than 4 weeks based on the RANO criteria. CR was defined as complete disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks, stable or improved non-enhancing (T2/FLAIR) lesions, no new lesions, participants must be off corticosteroids (or on physiologic replacement doses only), and clinically stable or improved. PR was defined as at least 50% decrease compared to Baseline in the size of all measurable enhancing lesions sustained for at least 4 weeks, no progression of non-measurable disease or any new lesions, stable of lower dose of corticosteroids than Baseline dose, and stable or improved non-enhancing (T2/FLAIR) lesions.
Time frame: Up to 42 months
Part 2: ORR (Non-Hodgkin's Lymphoma (NHL) Cohorts) Based on Lugano Criteria
ORR was defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) based on Lugano Criteria for Non-Hodgkin's lymphoma cohorts.
Time frame: Up to 42 months
Part 2: Overall Survival (OS) (ACC Tablet Cohort)
Overall survival (OS) was defined as time from first dose until death from any cause in ACC participants who are systemic-treatment naïve.
Time frame: Up to 42 months
Part 2: Progression-free Survival
PFS was defined as time from first dose until radiographic progression per standard criteria or death due to any cause, whichever is earlier.
Time frame: Up to 42 months
RP2D Phase: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
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 resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, or is a congenital anomaly/birth defect, other situations which involve medical or scientific judgment or was associated with liver injury and impaired liver function. SAEs are subset of AEs. AEs were coded using the MedDRA dictionary.
Time frame: Up to maximum 42 months
RP2D Phase: Number of Participants Withdrawn Due to AEs
The data for number of participants withdrawn due to AEs have been presented.
Time frame: Up to maximum 42 months
RP2D Phase: Number of Participants With Dose Modifications of GSK3326595
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Time frame: Up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Blood samples were collected for evaluation of clinical chemistry parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Blood samples were collected for evaluation of hematology parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Blood samples were collected for evaluation of coagulation parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v5.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Urine samples were collected for evaluation of urinalysis parameters. The summaries of worst case change from Baseline with respect to normal range have been presented for only those laboratory tests that are gradable by CTCAE v4.0. The number of participants with 'decreases to low', 'changes to normal' or 'no changes from Baseline', and 'increases to high' values have been presented.
Time frame: Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Changes From Baseline in Urine Potential of Hydrogen (pH)
Urine samples were collected from participants to assess urine pH levels.
Time frame: Baseline (Day 1) and up to Week 184
RP2D Phase: Changes From Baseline in Urine Specific Gravity
Urine samples were collected from participants to assess urine specific gravity.
Time frame: Baseline (Day 1) and up to Week 184
RP2D Phase: Number of Participants With Worst-case Increase Post-baseline Relative to Baseline in Vital Signs
Vital signs were measured. The abnormal vital sign ranges are: Heart Rate:- Low \[\<60 beats per minute (bpm)\], Normal (\>=60 bpm to \<=100 bpm), High (\>100 bpm); Temperature:- Low (\<=35 C), Normal (\>35 C and \<38 C), High (\>=38 C); Systolic Blood Pressure:- Low (\<90 mmHg), Normal (\>=90 mmHg to \<120 mmHg), High (\>=120 mmHg); Diastolic Blood Pressure:- Low (\<60 mmHg), Normal (\>=60 mmHg to \<80 mmHg), High (\>=80 mmHg). Participants were counted in the worst-case category that their value changes to (low, normal or high), unless there is no change in their category. Participants whose value category was unchanged (e.g., High to High), or whose value became normal, are recorded in the "To Normal or No Change" category. Participants were counted twice if the participants have values that changed 'To Low' and 'To High', so the percentages may not add to 100%.
Time frame: Baseline (Day 1) and up to maximum 42 months