CompletedNCT02783300Meteor 1Updated Mar 10, 2025Results posted

An Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK3326595 in Participants With Solid Tumors and Non-Hodgkin's Lymphoma

A Phase 1 interventional study of GSK3326595 and Pembrolizumab in Neoplasms, sponsored by GlaxoSmithKline. Completed at 15 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-03-10.

Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 297
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

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).

Conditions studied

Neoplasms

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Keywords

GSK3326595
Solid tumor
Non-Hodgkin's lymphoma (NHL)
Urinary tract cancer
Dose escalation
Adenoid cystic carcinoma (ACC)
Non small-cell lung cancer (NSCLC)
Squamous cell carcinoma of the head and neck (HNSCC)
Melanoma

In context

Lymphoma

5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.

This study's enrollment of 297 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained)
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
Diagnosis of non-resectable or metastatic solid malignancy (as defined in the protocol) or NHL
Presence of evaluable disease
Adequate organ function (as defined in the protocol)
Reproductive criteria (as defined in the protocol).

Exclusion criteria

Exclusion Criteria:

Malignancy attributed to prior solid organ transplant
Leptomeningeal disease, spinal cord compression, or brain metastases that require immediate central nervous system (CNS)-specific treatment in the opinion of the Investigator (for example [e.g.], for symptomatic disease)
History of a second malignancy, excluding non-melanoma skin cell cancer within the last three years
Evidence of severe or uncontrolled systemic diseases, or serious and/or pre-existing medical or other condition that could interfere with participant's safety, obtaining informed consent or compliance to the study procedures, in the opinion of the Investigator
Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
Select cardiac abnormalities (as defined in the protocol)
History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.
History of optic nerve neuropathy or neuritis.

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 297 participants (actual)

Study arms

Experimental
Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet
Participants will receive escalating doses of GSK3326595 until the maximum tolerated dose level is reached. The recommended phase 2 dose (RP2D) will be determined. Participants will be dosed in a fed (high-fat, high-calorie meal) and fasted state to determine the effect of food on bioavailability of GSK3326595, and will be dosed with tablet and capsule to compare two formulations of GSK3326595 (capsule versus tablet).
Drug: GSK3326595
Experimental
Part 2: Disease-Specific Expansion cohort
Participants with triple-negative breast cancer (TNBC), metastatic transitional cell carcinoma of the urinary system (mTCC), Grade IV anaplastic astrocytoma (glioblastoma multiforme \[GBM\]), non-Hodgkin's lymphoma (NHL), adenoid cystic carcinoma (ACC), hormone receptor-positive adenocarcinoma of the breast (ER+BC), human papillomavirus (HPV)-positive solid tumors of any histology, and p53-wild type non-small cell lung cancer (NSCLC) will be administered GSK3326595 at the recommended phase 2 dose (RP2D) as determined in Part 1.
Drug: GSK3326595
Experimental
Part 3: GSK3326595 in combination with pembrolizumab
Participants with selected solid tumors will be administered GSK3326595 in combination with pembrolizumab as part of this dose determination study.
Drug: GSK3326595 · Drug: Pembrolizumab

Interventions

DrugGSK3326595
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
DrugPembrolizumab
Pembrolizumab will be administered.

What researchers measure

Primary outcomes

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
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

Secondary outcomes

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

Results

Posted Mar 10, 2025

Limitations and caveats

Data was not available for pharmacokinetic parameters in samples that were out of stability or lost in transit.

Participant flow

Part 1- Dose Escalation Phase

Participant flow — Part 1- Dose Escalation Phase
Milestone	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Started	1	1	1	1	8	3	19	3	1	7	6	3	15
Completed	1	1	1	0	7	3	13	3	1	6	6	3	8
Not completed	0	0	0	1	1	0	6	0	0	1	0	0	7
Withdrew: Site terminated by sponsor	0	0	0	0	0	0	1	0	0	0	0	0	0
Withdrew: Lost to follow-up	0	0	0	1	0	0	0	0	0	0	0	0	0
Withdrew: Other reasons	0	0	0	0	0	0	0	0	0	0	0	0	2
Withdrew: Investigator discretion	0	0	0	0	0	0	4	0	0	0	0	0	3
Withdrew: Withdrawal by subject	0	0	0	0	1	0	1	0	0	1	0	0	2

Part 2- Disease-specific Expansion Phase

Participant flow — Part 2- Disease-specific Expansion Phase
Milestone	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Started	22	16	29	37	28	34	16	6	2	8	2	11	7
Completed	16	10	22	31	25	20	3	4	1	5	1	7	3
Not completed	6	6	7	6	3	14	13	2	1	3	1	4	4
Withdrew: Lost to follow-up	0	0	1	0	2	2	1	0	0	0	0	1	0
Withdrew: Site terminated by sponsor	0	0	0	1	0	1	2	0	0	0	0	0	0
Withdrew: Other reasons	0	0	0	1	0	1	3	1	0	0	0	0	0
Withdrew: Investigator site closed	0	0	1	0	0	0	0	0	0	1	0	0	0
Withdrew: Withdrawal by subject	1	3	2	1	0	7	2	0	0	0	0	0	0
Withdrew: Investigator discretion	5	3	3	3	1	3	5	1	1	2	1	3	4

Part 3- Dose Determination Phase

Participant flow — Part 3- Dose Determination Phase
Milestone	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Started	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	10
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	6
Not completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	4
Withdrew: Withdrawal by subject	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Withdrew: Investigator discretion	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3

Outcome measures

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Any AEs	1	1	1	1	7	3	19	3	1	7	6	3	15
Any SAEs	0	0	0	0	4	1	10	1	0	2	3	3	6

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants Withdrawn Due to AEs
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Part 1: Number of Participants Withdrawn Due to AEs	0	0	0	0	2	0	2	0	0	0	0	1	1

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)	0	0	0	0	0	1	2	0	0	0	1	1	0

PrimaryPart 1: 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 30 months
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Dose Modifications of GSK3326595
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Dose interruptions	1	1	1	1	5	3	18	2	0	5	4	2	14
Dose reductions	0	0	0	0	0	1	16	2	0	2	2	3	4

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Alanine Aminotransferase, decreases to low	0	0	0	0	2	0	4	1	0	0	1	1	4
Alanine Aminotransferase, changes to normal or no changes	0	1	1	1	4	1	13	1	1	6	4	2	11
Alanine Aminotransferase, increases to high	1	0	0	0	1	2	2	1	0	1	1	0	0
Albumin, decreases to low	1	1	1	1	4	1	12	1	0	2	5	1	7
Albumin, changes to normal or no changes	0	0	0	0	3	2	7	2	1	5	1	2	8
Albumin, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Alkaline Phosphatase, decreases to low	0	0	0	0	0	0	0	0	0	0	0	0	0
Alkaline Phosphatase, changes to normal or no changes	1	1	1	0	7	2	17	1	0	4	5	3	11
Alkaline Phosphatase, increases to high	0	0	0	1	0	1	2	2	1	3	1	0	4
Amylase, decreases to low	0	0	0	0	0	0	1	1	1	0	0	0	2
Amylase, changes to normal or no changes	1	1	1	1	7	3	15	2	0	6	5	3	13
Amylase, increases to high	0	0	0	0	0	0	3	0	0	1	1	0	0
Aspartate Aminotransferase, decreases to low	0	0	0	0	0	0	1	0	0	0	0	1	0
Aspartate Aminotransferase, changes to normal or no changes	0	1	0	0	4	2	11	2	0	6	4	2	11
Aspartate Aminotransferase, increases to high	1	0	1	1	3	1	7	1	1	1	2	0	4
Bilirubin, decreases to low	0	0	0	0	0	1	0	0	0	1	0	0	0
Bilirubin, changes to normal or no changes	1	1	1	1	5	2	13	2	0	3	4	2	13
Bilirubin, increases to high	0	0	0	0	2	0	6	1	1	3	2	1	2
Calcium, decreases to low	1	0	0	0	3	2	12	1	1	4	3	1	7
Calcium, changes to normal or no changes	0	1	1	1	2	1	7	2	0	3	3	2	8
Calcium, increases to high	0	0	0	0	2	0	0	0	0	0	0	0	0
Creatinine, decreases to low	0	0	1	1	0	0	1	0	0	1	1	0	2
Creatinine, changes to normal or no changes	1	1	0	0	6	3	16	3	1	6	4	3	11
Creatinine, increases to high	0	0	0	0	1	0	2	0	0	0	1	0	2
Direct Bilirubin, decreases to low	0	0	0	0	0	0	0	0	0	0	0	0	0
Direct Bilirubin, changes to normal or no changes	1	1	1	1	3	2	11	2	0	2	4	1	9
Direct Bilirubin, increases to high	0	0	0	0	4	1	8	1	1	5	2	2	6
Glucose, decreases to low	0	0	0	0	0	0	0	1	0	0	0	0	1
Glucose, changes to normal or no changes	1	1	1	1	6	3	9	1	0	4	5	0	11
Glucose, increases to high	0	0	0	0	1	0	10	1	1	3	1	3	3
Lipase, decreases to low	0	0	0	0	0	0	1	0	0	0	1	0	2
Lipase, changes to normal or no changes	1	1	1	1	7	2	15	3	1	6	5	1	13
Lipase, increases to high	0	0	0	0	0	1	3	0	0	1	0	2	0
Potassium, decreases to low	0	0	0	0	1	1	1	1	0	1	2	0	5
Potassium, changes to normal or no changes	1	1	1	1	5	2	13	2	1	4	3	1	9
Potassium, increases to high	0	0	0	0	1	0	5	0	0	2	3	2	1
Protein, decreases to low	1	0	0	0	3	0	12	1	0	4	4	1	6
Protein, changes to normal or no changes	0	1	1	1	4	3	6	2	1	3	2	2	8
Protein, increases to high	0	0	0	0	0	0	1	0	0	0	0	0	1
Sodium, decreases to low	0	0	0	0	3	1	4	0	0	2	2	0	2
Sodium, changes to normal or no changes	1	1	1	1	3	2	14	3	1	5	3	3	11
Sodium, increases to high	0	0	0	0	1	0	1	0	0	0	1	0	2
Urea Nitrogen, decreases to low	0	0	0	1	1	0	0	0	1	0	0	0	1
Urea Nitrogen, changes to normal or no changes	1	1	1	0	3	2	9	2	0	2	2	2	11
Urea Nitrogen, increases to high	0	0	0	0	4	0	6	1	0	3	2	0	3

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Basophils, decreases to low	0	0	0	0	0	0	0	0	0	0	0	0	0
Basophils, changes to normal or no changes	1	1	1	1	6	2	19	3	1	7	6	2	15
Basophils, increases to high	0	0	0	0	1	1	0	0	0	0	0	1	0
Eosinophils, decreases to low	0	1	0	0	2	0	1	0	0	0	0	0	1
Eosinophils, changes to normal or no changes	1	0	1	1	5	3	16	3	1	6	6	0	14
Eosinophils, increases to high	0	0	0	0	0	0	2	0	0	1	0	3	0
Mean Corpuscular Hemoglobin, decreases to low	0	0	0	0	2	0	1	0	0	2	0	1	6
Mean Corpuscular Hemoglobin, changes to normal or no changes	1	1	1	1	5	3	17	2	0	5	6	1	9
Mean Corpuscular Hemoglobin, increases to high	0	0	0	0	0	0	1	1	1	0	0	1	0
Mean Corpuscular Volume, decreases to low	0	0	0	0	0	0	1	0	0	0	0	0	0
Mean Corpuscular Volume, changes to normal or no changes	0	1	1	1	7	2	16	3	1	7	5	3	15
Mean Corpuscular Volume, increases to high	1	0	0	0	0	1	2	0	0	0	1	0	0
Erythrocytes, decreases to low	0	0	0	0	1	1	12	0	0	3	3	1	7
Erythrocytes, changes to normal or no changes	1	1	1	1	6	2	7	2	1	4	3	2	8
Erythrocytes, increases to high	0	0	0	0	0	0	0	1	0	1	0	0	0
Hematocrit, decreases to low	0	0	0	0	2	2	14	1	0	2	2	2	5
Hematocrit, changes to normal or no changes	1	1	1	1	5	1	5	2	1	5	4	1	10
Hematocrit, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Hemoglobin, decreases to low	0	1	0	0	2	2	11	0	1	2	3	1	6
Hemoglobin, changes to normal or no changes	1	0	1	1	5	1	8	3	0	5	3	2	9
Hemoglobin, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Leukocytes, decreases to low	1	0	0	0	2	2	8	1	0	4	1	2	8
Leukocytes, changes to normal or no changes	0	1	0	1	4	1	9	2	1	2	3	1	7
Leukocytes, increases to high	0	0	1	0	2	0	3	0	0	1	2	1	0
Lymphocytes, decreases to low	0	0	0	0	0	2	7	2	1	2	3	2	4
Lymphocytes, changes to normal or no changes	1	1	1	1	7	1	12	1	0	5	3	1	11
Lymphocytes, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Monocytes, decreases to low	0	1	0	0	0	2	4	0	0	0	1	0	0
Monocytes, changes to normal or no changes	1	0	1	1	4	1	10	3	1	7	3	2	12
Monocytes, increases to high	0	0	0	0	3	0	5	0	0	0	3	1	3
Neutrophils, decreases to low	0	0	0	0	0	2	5	0	0	2	1	2	4
Neutrophils, changes to normal or no changes	1	1	0	1	4	1	9	1	1	3	2	1	10
Neutrophils, increases to high	0	0	1	0	3	0	5	2	0	2	3	1	2
Neutrophils/ Leukocytes, decreases to low	0	—	0	—	—	0	2	0	0	0	1	0	0
Neutrophils/ Leukocytes, changes to normal or no changes	1	—	1	—	—	1	5	2	1	2	0	1	6
Neutrophils/ Leukocytes, increases to high	0	—	0	—	—	0	1	1	0	1	1	0	2
Platelets, decreases to low	0	0	0	0	2	1	12	2	0	3	3	2	7
Platelets, changes to normal or no changes	1	1	1	1	4	2	4	1	1	4	3	0	7
Platelets, increases to high	0	0	0	0	2	0	3	0	0	0	0	1	2
Reticulocytes, decreases to low	0	0	0	0	2	0	13	2	0	0	2	2	4
Reticulocytes, changes to normal or no changes	1	1	1	1	2	1	2	0	1	3	2	1	4
Reticulocytes, increases to high	0	0	0	0	2	2	13	2	0	4	2	1	8

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Partial Thromboplastin Time, decreases to low	0	0	0	0	0	0	1	0	1	0	0	0	1
Partial Thromboplastin Time, changes to normal or no changes	1	0	1	0	4	1	8	1	0	4	1	1	7
Partial Thromboplastin Time, increases to high	0	1	0	1	3	1	6	2	0	1	3	1	7
Prothrombin Intl. Normalized Ratio, decreases to low	0	0	0	0	0	0	1	0	0	0	0	0	0
Prothrombin Intl. Normalized Ratio, changes to normal or no changes	1	1	0	0	4	2	8	1	0	2	2	2	5
Prothrombin Intl. Normalized Ratio, increases to high	0	0	1	1	3	1	10	2	1	5	4	1	10
Prothrombin Time, decreases to low	0	0	0	0	0	0	1	0	0	0	0	0	0
Prothrombin Time, changes to normal or no changes	1	1	0	1	3	3	9	1	0	4	3	3	7
Prothrombin Time, increases to high	0	0	1	0	0	0	7	2	1	2	2	0	8

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Occult Blood, No Change or Change to Negative	0	1	0	1	5	2	12	2	1	4	4	1	10
Occult Blood, Change to Positive	1	0	1	0	2	1	7	1	0	3	2	2	5
Protein, No Change or Change to Negative	1	1	1	1	4	2	11	1	1	2	4	1	10
Protein, Change to Positive	0	0	0	0	3	1	8	2	0	5	2	2	5
Ketones, No Change or Change to Negative	1	1	1	1	5	2	11	2	0	3	3	3	8
Ketones, Change to Positive	0	0	0	0	2	1	8	1	1	4	3	0	7
Glucose, No Change or Change to Negative	1	1	1	1	7	3	18	3	1	7	5	3	11
Glucose, Change to Positive	0	0	0	0	0	0	1	0	0	0	1	0	4

PrimaryPart 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
Reported as:: Mean · Potential of Hydrogen (pH)

Part 1: Changes From Baseline in Urine Potential of Hydrogen (pH)
Potential of Hydrogen (pH)	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Baseline	5.00 ± NA	5.50 ± NA	7.00 ± NA	6.50 ± NA	6.00 ± 0.886	6.17 ± 0.289	6.11 ± 0.698	5.67 ± 0.764	6.50 ± NA	5.79 ± 1.075	5.75 ± 0.524	6.17 ± 0.764	5.63 ± 0.834
CFB to Day 8	0.00 ± NA	0.00 ± NA	-1.00 ± NA	0.50 ± NA	0.17 ± 0.516	-0.25 ± 0.354	-0.28 ± 0.548	0.83 ± 0.764	0.50 ± NA	-0.07 ± 1.239	0.08 ± 0.492	0.33 ± 1.258	-0.03 ± 0.516
CFB to Day 15	0.00 ± NA	0.00 ± NA	-1.00 ± NA	0.50 ± NA	0.21 ± 0.488	-0.17 ± 0.289	-0.24 ± 0.731	0.00 ± 1.000	0.00 ± NA	-0.29 ± 0.859	0.10 ± 0.548	1.00 ± NA	0.03 ± 0.719
CFB to Week 4 Day 1	0.00 ± NA	0.00 ± NA	0.00 ± NA	0.50 ± NA	-0.20 ± 0.447	-0.75 ± 0.354	-0.13 ± 0.611	0.67 ± 1.041	-0.50 ± NA	-0.21 ± 0.488	0.10 ± 0.548	—	-0.10 ± 0.849
CFB to Week 6 Day 1	0.00 ± NA	0.00 ± NA	0.00 ± NA	0.50 ± NA	-0.17 ± 0.577	0.00 ± 0.000	-0.43 ± 0.799	0.25 ± 1.061	-0.50 ± NA	-0.29 ± 1.035	-0.08 ± 0.492	0.00 ± 0.707	-0.04 ± 0.865
CFB to Week 8	0.00 ± NA	-0.50 ± NA	—	0.50 ± NA	-1.17 ± 1.155	-0.75 ± 0.354	-0.19 ± 0.630	1.00 ± 0.707	—	0.75 ± 0.645	-0.20 ± 0.274	0.00 ± 0.000	0.44 ± 0.682
CFB to Week 12	0.00 ± NA	—	—	—	0.00 ± 0.500	-0.50 ± NA	-0.11 ± 0.546	1.00 ± 1.414	—	0.38 ± 0.629	0.00 ± NA	-0.25 ± 1.061	0.08 ± 1.021
CFB to Week 16	—	—	—	—	-0.25 ± 1.061	0.00 ± NA	0.14 ± 0.690	0.50 ± 1.414	—	0.33 ± 0.289	0.00 ± NA	0.00 ± 0.000	-0.13 ± 0.250
CFB to Week 20	—	—	—	—	-0.75 ± 0.354	—	0.00 ± 0.548	-0.50 ± 0.000	—	0.00 ± 0.000	0.00 ± NA	0.50 ± 0.707	-0.13 ± 0.854
CFB to Week 24	—	—	—	—	-0.75 ± 1.768	—	0.10 ± 0.418	0.75 ± 1.768	—	1.00 ± 1.414	0.00 ± NA	0.50 ± 0.707	-0.60 ± 0.418
CFB to Week 28	—	—	—	—	-1.25 ± 1.061	—	-0.13 ± 0.479	-0.25 ± 0.354	—	1.50 ± 0.707	—	-0.50 ± NA	-0.40 ± 0.418
CFB to Week 32	—	—	—	—	-1.00 ± 0.707	—	0.00 ± 0.408	0.00 ± NA	—	0.25 ± 0.354	—	0.75 ± 0.354	0.10 ± 1.194
CFB to Week 36	—	—	—	—	-1.00 ± 0.707	—	0.00 ± 0.000	0.00 ± NA	—	0.50 ± 0.000	—	0.00 ± 0.000	-0.63 ± 0.479
CFB to Week 40	—	—	—	—	-1.50 ± 1.414	—	-0.17 ± 0.289	—	—	1.00 ± 1.414	—	0.50 ± 0.707	-0.20 ± 0.758
CFB to Week 44	—	—	—	—	0.25 ± 0.354	—	0.00 ± 0.000	—	—	0.25 ± 0.354	—	1.50 ± NA	-0.13 ± 0.854
CFB to Week 48	—	—	—	—	0.75 ± 0.354	—	-0.17 ± 0.289	—	—	0.50 ± 0.000	—	1.00 ± NA	-0.50 ± 0.707
CFB to Week 52	—	—	—	—	-0.50 ± 0.707	—	0.50 ± 0.500	—	—	0.50 ± NA	—	1.00 ± NA	-0.30 ± 0.274
CFB to Week 56	—	—	—	—	—	—	0.00 ± 0.000	—	—	0.00 ± NA	—	1.00 ± NA	-0.83 ± 0.289
CFB to Week 60	—	—	—	—	—	—	-0.25 ± 0.354	—	—	0.50 ± NA	—	-0.50 ± NA	-1.00 ± 0.500
CFB to Week 64	—	—	—	—	—	—	0.00 ± NA	—	—	0.00 ± NA	—	-0.50 ± NA	-0.33 ± 0.764
CFB to Week 68	—	—	—	—	—	—	-0.25 ± 0.354	—	—	1.50 ± NA	—	0.00 ± NA	-0.25 ± 0.866
CFB to Week 72	—	—	—	—	—	—	-0.25 ± 0.354	—	—	0.50 ± NA	—	0.50 ± NA	-0.33 ± 0.764
CFB to Week 76	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	0.50 ± NA	-0.75 ± 0.354
CFB to Week 80	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	0.00 ± 0.866
CFB to Week 84	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	0.00 ± NA
CFB to Week 88	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	-0.25 ± 1.061
CFB to Week 92	—	—	—	—	—	—	-1.00 ± NA	—	—	—	—	1.00 ± NA	-0.75 ± 0.354
CFB to Week 96	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	-0.33 ± 0.289
CFB to Week 100	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	-0.25 ± 0.354
CFB to Week 104	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	-0.83 ± 0.289
CFB to Week 108	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	-0.50 ± NA	-1.00 ± 0.000
CFB to Week 112	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	1.00 ± NA	-0.50 ± 0.866
CFB to Week 116	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—	-0.75 ± 0.354
CFB to Week 120	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—	-0.33 ± 0.289
CFB to Week 124	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—	-0.50
CFB to Week 128	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	—	-0.33 ± 0.764
CFB to Week 132	—	—	—	—	—	—	0.50 ± NA	—	—	—	—	—	—

PrimaryPart 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
Reported as:: Mean · Ratio

Part 1: Changes From Baseline in Urine Specific Gravity
Ratio	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Baseline	1.02 ± NA	1.03 ± NA	1.01 ± NA	1.02 ± NA	1.02 ± 0.008	1.02 ± 0.006	1.02 ± 0.007	1.02 ± 0.004	1.01 ± NA	1.02 ± 0.006	1.03 ± 0.008	1.02 ± 0.008	1.02 ± 0.007
CFB to Day 8	-0.01 ± NA	0.00 ± NA	0.01 ± NA	0.01 ± NA	0.00 ± 0.010	0.00 ± 0.004	0.00 ± 0.007	0.00 ± 0.010	0.00 ± NA	0.00 ± 0.008	0.00 ± 0.006	0.00 ± 0.009	0.00 ± 0.008
CFB to Day 15	-0.01 ± NA	-0.01 ± NA	0.01 ± NA	0.00 ± NA	0.00 ± 0.010	-0.01 ± 0.005	0.00 ± 0.007	0.00 ± 0.005	0.01 ± NA	0.00 ± 0.010	0.00 ± 0.004	0.00	0.00 ± 0.008
CFB to Week 4 Day 1	-0.01 ± NA	-0.01 ± NA	0.00 ± NA	0.00 ± NA	0.00 ± 0.007	0.00 ± 0.004	0.00 ± 0.008	0.00 ± 0.002	0.01 ± NA	0.00 ± 0.007	0.00 ± 0.007	—	0.00 ± 0.007
CFB to Week 6 Day 1	-0.01 ± NA	-0.01 ± NA	0.01 ± NA	0.01 ± NA	0.00 ± 0.008	-0.01 ± 0.004	0.00 ± 0.010	0.00 ± 0.006	0.01 ± NA	0.00 ± 0.012	0.00 ± 0.004	-0.01 ± 0.007	0.00 ± 0.006
CFB to Week 8	-0.01 ± NA	0.00 ± NA	—	0.01 ± NA	0.00 ± 0.008	-0.01 ± 0.004	0.00 ± 0.008	0.00 ± 0.006	—	0.00 ± 0.006	0.00 ± 0.004	-0.01 ± 0.007	0.00 ± 0.007
CFB to Week 12	-0.01 ± NA	—	—	—	0.00 ± 0.005	-0.01	0.00 ± 0.008	-0.01 ± 0.008	—	0.00 ± 0.010	-0.01 ± NA	-0.01 ± 0.004	0.00 ± 0.006
CFB to Week 16	—	—	—	—	0.00 ± 0.011	-0.02 ± NA	0.00 ± 0.006	-0.01 ± 0.004	—	-0.01 ± 0.008	0.00 ± NA	0.00 ± 0.004	0.00 ± 0.004
CFB to Week 20	—	—	—	—	0.00 ± 0.004	—	0.00 ± 0.008	0.00 ± 0.002	—	0.00 ± 0.007	0.00 ± NA	-0.01 ± 0.004	0.00 ± 0.003
CFB to Week 24	—	—	—	—	0.00 ± 0.011	—	0.00 ± 0.004	0.00 ± 0.004	—	0.00 ± 0.006	0.00 ± NA	-0.01 ± 0.000	0.00 ± 0.002
CFB to Week 28	—	—	—	—	0.00 ± 0.011	—	0.00 ± 0.012	0.00 ± 0.004	—	0.00 ± 0.015	—	-0.01 ± NA	0.00 ± 0.006
CFB to Week 32	—	—	—	—	0.00 ± 0.004	—	0.00 ± 0.007	0.01 ± NA	—	0.00 ± 0.014	—	0.00 ± 0.004	0.00 ± 0.003
CFB to Week 36	—	—	—	—	-0.01 ± 0.014	—	0.01 ± 0.013	0.01 ± NA	—	0.00 ± 0.008	—	0.01 ± 0.011	0.00 ± 0.002
CFB to Week 40	—	—	—	—	0.00 ± 0.014	—	0.00 ± 0.012	—	—	0.00 ± 0.015	—	-0.01 ± 0.000	0.00 ± 0.003
CFB to Week 44	—	—	—	—	0.00 ± 0.014	—	0.00 ± 0.008	—	—	0.00 ± 0.010	—	-0.01	0.00 ± 0.004
CFB to Week 48	—	—	—	—	-0.01 ± 0.014	—	0.00 ± 0.006	—	—	0.00 ± 0.010	—	-0.01 ± NA	0.00 ± 0.005
CFB to Week 52	—	—	—	—	0.00 ± 0.018	—	0.00 ± 0.009	—	—	0.01 ± NA	—	-0.01 ± NA	0.00 ± 0.004
CFB to Week 56	—	—	—	—	—	—	-0.01 ± 0.004	—	—	0.01 ± NA	—	0.01 ± NA	0.00 ± 0.005
CFB to Week 60	—	—	—	—	—	—	-0.01 ± 0.004	—	—	0.01 ± NA	—	-0.01 ± NA	0.00 ± 0.006
CFB to Week 64	—	—	—	—	—	—	-0.01 ± NA	—	—	0.01 ± NA	—	-0.01 ± NA	0.00 ± 0.007
CFB to Week 68	—	—	—	—	—	—	-0.01 ± 0.000	—	—	0.01 ± NA	—	-0.01 ± NA	0.00 ± 0.003
CFB to Week 72	—	—	—	—	—	—	0.00 ± 0.007	—	—	0.01 ± NA	—	-0.01 ± NA	0.00 ± 0.002
CFB to Week 76	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	-0.01 ± NA	0.00 ± 0.004
CFB to Week 80	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	0.00 ± NA	0.00 ± 0.006
CFB to Week 84	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	0.00 ± NA	0.00 ± NA
CFB to Week 88	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	0.00 ± NA	0.00 ± 0.003
CFB to Week 92	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	0.00 ± NA	0.00 ± 0.006
CFB to Week 96	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	0.01 ± NA	0.00 ± 0.003
CFB to Week 100	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	0.01 ± NA	0.00 ± 0.001
CFB to Week 104	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	0.01 ± NA	-0.01 ± 0.008
CFB to Week 108	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	-0.01 ± NA	0.00 ± 0.004
CFB to Week 112	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	-0.01 ± NA	0.00 ± 0.007
CFB to Week 116	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	—	0.00 ± 0.004
CFB to Week 120	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	—	0.01 ± 0.008
CFB to Week 124	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	—	0.01 ± NA
CFB to Week 128	—	—	—	—	—	—	-0.01 ± NA	—	—	—	—	—	0.01 ± 0.008
CFB to Week 132	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—	—

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs
Participants	Part 1: GSK3326595 12.5 Milligram (mg) Once a Day (QD)	Part 1: GSK3326595 25mg QD	Part 1: GSK3326595 50mg QD	Part 1: GSK3326595 100mg QD	Part 1: GSK3326595 200mg QD	Part 1: GSK3326595 300mg QD	Part 1: GSK3326595 400mg QD	Part 1: GSK3326595 600mg QD	Part 1: GSK3326595 50mg Twice Daily (BID)	Part 1: GSK3326595 100mg BID	Part 1: GSK3326595 150mg BID	Part 1: GSK3326595 200mg BID	Part 1: GSK3326595 300mg QD (Food Effect)
Heart Rate, changes to low	0	0	0	0	1	0	2	0	0	1	0	0	2
Heart Rate, changes to normal or no changes	1	1	1	0	5	3	12	3	1	3	6	2	10
Heart Rate, changes to high	0	0	0	1	1	0	6	0	0	3	0	1	3
Temperature, changes to low	0	0	0	0	0	0	0	0	0	0	0	0	0
Temperature, changes to normal or no changes	1	1	1	1	6	3	17	3	1	6	6	3	15
Temperature, changes to high	0	0	0	0	1	0	2	0	0	1	0	0	0
Systolic Blood Pressure, changes to low	0	0	0	0	0	0	3	1	0	1	0	0	2
Systolic Blood Pressure, changes to normal or no changes	0	1	1	1	5	2	9	1	1	5	5	1	11
Systolic Blood Pressure, changes to high	1	0	0	0	2	1	7	1	0	1	1	2	2
Diastolic Blood Pressure, changes to low	0	0	0	0	1	2	6	1	0	0	0	1	3
Diastolic Blood Pressure, changes to normal or no changes	1	0	1	0	4	1	7	0	1	7	4	1	8
Diastolic Blood Pressure, changes to high	0	1	0	1	2	1	8	3	0	0	2	1	5

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Any AEs	9
Any SAEs	5

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants Withdrawn Due to AEs
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Part 3: Number of Participants Withdrawn Due to AEs	1

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Dose Modifications of GSK3326595 and Pembrolizumab
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Dose interruptions of GSK3326595	1
Dose reductions of GSK3326595	0
Dose Interruptions of Pembrolizumab	1
Dose reductions of Pembrolizumab	0

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Alanine Aminotransferase, decreases to low	2
Alanine Aminotransferase, changes to normal or no changes	3
Alanine Aminotransferase, increases to high	4
Albumin, decreases to low	3
Albumin, changes to normal or no changes	6
Albumin, increases to high	0
Alkaline Phosphatase, decreases to low	0
Alkaline Phosphatase, changes to normal or no changes	8
Alkaline Phosphatase, increases to high	1
Amylase, decreases to low	2
Amylase, changes to normal or no changes	6
Amylase, increases to high	1
Aspartate Aminotransferase, decreases to low	0
Aspartate Aminotransferase, changes to normal or no changes	6
Aspartate Aminotransferase, increases to high	3
Bilirubin, decreases to low	0
Bilirubin, changes to normal or no changes	7
Bilirubin, increases to high	2
Calcium, decreases to low	7
Calcium, changes to normal or no changes	2
Calcium, increases to high	0
Creatinine, decreases to low	0
Creatinine, changes to normal or no changes	8
Creatinine, increases to high	1
Direct Bilirubin, decreases to low	0
Direct Bilirubin, changes to normal or no changes	6
Direct Bilirubin, increases to high	3
Glucose, decreases to low	0
Glucose, changes to normal or no changes	7
Glucose, increases to high	2
Lipase, decreases to low	2
Lipase, changes to normal or no changes	6
Lipase, increases to high	1
Potassium, decreases to low	4
Potassium, changes to normal or no changes	4
Potassium, increases to high	1
Protein, decreases to low	5
Protein, changes to normal or no changes	3
Protein, increases to high	1
Sodium, decreases to low	2
Sodium, changes to normal or no changes	6
Sodium, increases to high	1
Urea Nitrogen, decreases to low	0
Urea Nitrogen, changes to normal or no changes	4
Urea Nitrogen, increases to high	1

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Basophils, decreases to low	0
Basophils, changes to normal or no changes	9
Basophils, increases to high	0
Eosinophils, decreases to low	0
Eosinophils, changes to normal or no changes	8
Eosinophils, increases to high	1
Mean Corpuscular Hemoglobin, decreases to low	1
Mean Corpuscular Hemoglobin, changes to normal or no changes	8
Mean Corpuscular Hemoglobin, increases to high	0
Mean Corpuscular Volume, decreases to low	1
Mean Corpuscular Volume, changes to normal or no changes	7
Mean Corpuscular Volume, increases to high	1
Erythrocytes, decreases to low	1
Erythrocytes, changes to normal or no changes	8
Erythrocytes, increases to high	0
Hematocrit, decreases to low	0
Hematocrit, changes to normal or no changes	9
Hematocrit, increases to high	0
Hemoglobin, decreases to low	2
Hemoglobin, changes to normal or no changes	7
Hemoglobin, increases to high	0
Leukocytes, decreases to low	3
Leukocytes, changes to normal or no changes	5
Leukocytes, increases to high	1
Lymphocytes, decreases to low	5
Lymphocytes, changes to normal or no changes	4
Lymphocytes, increases to high	0
Monocytes, decreases to low	0
Monocytes, changes to normal or no changes	8
Monocytes, increases to high	1
Neutrophils, decreases to low	1
Neutrophils, changes to normal or no changes	7
Neutrophils, increases to high	1
Platelets, decreases to low	1
Platelets, changes to normal or no changes	6
Platelets, increases to high	2
Reticulocytes, decreases to low	0
Reticulocytes, changes to normal or no changes	5
Reticulocytes, increases to high	3

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Partial Thromboplastin Time, decreases to low	1
Partial Thromboplastin Time, changes to normal or no changes	5
Partial Thromboplastin Time, increases to high	3
Prothrombin Intl. Normalized Ratio, decreases to low	1
Prothrombin Intl. Normalized Ratio, changes to normal or no changes	6
Prothrombin Intl. Normalized Ratio, increases to high	2
Prothrombin Time, decreases to low	1
Prothrombin Time, changes to normal or no changes	4
Prothrombin Time, increases to high	4

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Occult Blood, No Change or Change to Negative	7
Occult Blood, Change to Positive	3
Protein, No Change or Change to Negative	8
Protein, Change to Positive	2
Ketones, No Change or Change to Negative	7
Ketones, Change to Positive	3
Glucose, No Change or Change to Negative	10
Glucose, Change to Positive	0

PrimaryPart 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
Reported as:: Mean · Potential of Hydrogen (pH)

Part 3: Changes From Baseline in Urine Potential of Hydrogen (pH)
Potential of Hydrogen (pH)	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Baseline	5.60 ± 0.937
CFB to Day 1	0.00 ± NA
CFB to Day 8	0.38 ± 0.582
CFB to Day 15	0.33 ± 0.750
CFB to Week 4 Day 1	0.33 ± 0.500
Week 6 Day 1	0.31 ± 0.704
CFB to Week 8	0.25 ± 0.354
CFB to Week 9	0.33 ± 0.577
CFB to Week 12	0.83 ± 0.764
CFB to Week 15	0.67 ± 0.289
CFB to Week 18	0.50 ± 0.500
CFB to Week 21	0.50 ± 0.500
CFB to Week 24	0.25 ± 0.354
CFB to Week 27	0.25 ± 0.354
CFB to Week 30	0.00 ± NA
CFB to Week 33	0.00 ± NA
CFB to Week 36	0.00 ± NA
CFB to Week 39	0.00 ± NA
CFB to Week 42	0.00 ± NA

PrimaryPart 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
Reported as:: Mean · Ratio

Part 3: Changes From Baseline in Urine Specific Gravity
Ratio	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Baseline	1.02 ± 0.008
CFB to Day 1	0.00 ± NA
CFB to Day 8	-0.01 ± 0.009
CFB to Day 15	0.00 ± 0.006
CFB to Week 4 Day 1	-0.01 ± 0.008
CFB to Week 6 Day 1	0.00 ± 0.007
CFB to Week 8	0.00 ± 0.001
CFB to Week 9	-0.01 ± 0.003
CFB to Week 12	-0.01 ± 0.006
CFB to Week 15	0.00 ± 0.008
CFB to Week 18	-0.01 ± 0.007
CFB to Week 21	0.00 ± 0.009
CFB to Week 24	-0.01 ± 0.001
CFB to Week 27	0.00 ± 0.016
CFB to Week 30	0.00 ± NA
CFB to Week 33	0.00 ± NA
CFB to Week 36	0.00 ± NA
CFB to Week 39	0.01 ± NA
CFB to Week 42	0.01 ± NA

PrimaryPart 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
Reported as:: Count of participants · Participants

Part 3: Number of Participants With Maximum Worst-case Increase Post-baseline Relative to Baseline in Vital Signs
Participants	Part 3: GSK3326595 100mg + Pembrolizumab 200mg
Heart Rate, changes to low	0
Heart Rate, changes to normal or no changes	6
Heart Rate, changes to high	3
Temperature, changes to low	0
Temperature, changes to normal or no changes	9
Temperature, changes to high	0
Systolic Blood Pressure, changes to low	0
Systolic Blood Pressure, changes to normal or no changes	5
Systolic Blood Pressure, changes to high	4
Diastolic Blood Pressure, changes to low	2
Diastolic Blood Pressure, changes to normal or no changes	2
Diastolic Blood Pressure, changes to high	6

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Any AEs	22	16	27	37	28	34	16	6	2	8	2	11	7
Any SAEs	13	7	15	10	13	15	5	4	2	4	0	4	0

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants Withdrawn Due to AEs
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Part 2: Number of Participants Withdrawn Due to AEs	4	4	4	3	1	3	2	1	0	1	0	3	1

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Dose Modifications of GSK3326595
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Dose interruptions	13	12	11	22	20	28	13	4	2	3	2	5	2
Dose reductions	8	11	11	26	18	27	7	4	2	4	0	6	3

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Alanine Aminotransferase, decreases to low	1	1	0	2	1	9	7	0	0	0	0	0	1
Alanine Aminotransferase, changes to normal or no changes	20	12	24	30	25	23	9	5	2	7	2	10	6
Alanine Aminotransferase, increases to high	1	3	4	6	2	2	0	1	0	1	0	1	0
Albumin, decreases to low	8	6	6	15	11	19	7	3	0	4	0	3	0
Albumin, changes to normal or no changes	14	10	22	22	17	14	9	3	2	4	2	8	7
Albumin, increases to high	0	0	0	0	0	1	0	0	0	0	0	0	0
Alkaline Phosphatase, decreases to low	0	0	0	0	0	0	0	1	0	0	0	0	0
Alkaline Phosphatase, changes to normal or no changes	19	10	27	30	24	26	14	3	1	5	2	9	4
Alkaline Phosphatase, increases to high	3	6	1	7	4	8	2	2	1	3	0	2	3
Amylase, decreases to low	1	1	0	4	4	1	1	1	0	0	0	0	2
Amylase, changes to normal or no changes	19	10	25	31	23	28	14	3	2	7	2	10	5
Amylase, increases to high	2	5	3	2	2	5	1	2	0	1	0	1	0
Aspartate Aminotransferase, decreases to low	0	0	0	0	0	2	1	0	0	0	0	1	0
Aspartate Aminotransferase, changes to normal or no changes	15	12	25	30	22	19	15	4	1	6	1	8	6
Aspartate Aminotransferase, increases to high	7	4	3	7	6	13	0	2	1	2	1	2	1
Bilirubin, decreases to low	0	0	1	0	0	0	1	0	0	1	0	0	0
Bilirubin, changes to normal or no changes	17	11	22	30	25	30	11	5	1	7	2	10	7
Bilirubin, increases to high	5	5	5	7	3	4	4	1	1	0	0	1	0
Calcium, decreases to low	6	7	9	8	10	11	3	6	1	5	0	5	3
Calcium, changes to normal or no changes	16	9	19	25	17	23	13	0	1	3	2	5	4
Calcium, increases to high	0	1	0	5	1	0	0	0	0	0	0	1	0
Creatinine, decreases to low	5	0	3	5	5	6	4	0	0	0	1	1	1
Creatinine, changes to normal or no changes	15	10	22	24	17	25	12	3	2	6	1	7	5
Creatinine, increases to high	2	6	3	8	6	3	1	3	0	2	0	3	1
Direct Bilirubin, decreases to low	0	0	0	0	0	0	0	0	0	0	0	0	0
Direct Bilirubin, changes to normal or no changes	15	7	16	27	23	20	10	4	1	5	0	6	7
Direct Bilirubin, increases to high	7	9	12	10	5	14	6	2	1	3	2	4	0
Glucose, decreases to low	2	2	0	3	2	4	2	0	0	1	0	0	2
Glucose, changes to normal or no changes	14	10	25	24	13	16	9	3	1	2	2	7	3
Glucose, increases to high	6	5	3	10	14	15	6	3	1	6	0	4	2
Lipase, decreases to low	1	1	1	1	0	3	1	1	0	0	0	0	1
Lipase, changes to normal or no changes	19	12	21	31	25	26	15	4	2	7	1	11	5
Lipase, increases to high	2	3	6	5	3	6	0	1	0	1	1	0	1
Potassium, decreases to low	3	4	3	5	5	2	1	0	1	0	0	1	0
Potassium, changes to normal or no changes	18	11	21	25	19	23	12	2	1	6	1	10	4
Potassium, increases to high	2	2	4	7	6	10	3	4	0	2	1	0	3
Protein, decreases to low	8	4	12	7	12	13	7	4	1	5	1	7	3
Protein, changes to normal or no changes	13	10	16	28	16	20	9	2	1	3	1	4	4
Protein, increases to high	1	3	0	2	0	1	0	0	0	0	0	0	0
Sodium, decreases to low	6	5	1	8	6	6	4	1	0	1	0	3	1
Sodium, changes to normal or no changes	13	9	25	29	22	25	10	4	2	7	2	7	6
Sodium, increases to high	3	2	2	1	0	4	2	1	0	0	0	1	0
Urea Nitrogen, decreases to low	0	0	0	2	1	2	2	0	—	0	—	0	0
Urea Nitrogen, changes to normal or no changes	3	5	9	11	7	8	6	0	—	3	—	2	1
Urea Nitrogen, increases to high	0	5	5	5	6	8	6	2	—	0	—	3	1

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Basophils, decreases to low	0	0	0	2	2	1	0	0	0	0	0	0	0
Basophils, changes to normal or no changes	21	16	24	35	26	33	16	5	2	5	2	8	7
Basophils, increases to high	0	0	1	0	1	0	0	0	0	1	0	0	0
Eosinophils, decreases to low	0	0	2	2	2	3	2	1	0	0	0	2	0
Eosinophils, changes to normal or no changes	21	14	23	33	26	29	14	4	2	6	2	5	4
Eosinophils, increases to high	0	2	0	2	0	2	1	0	0	0	0	1	3
Mean Corpuscular Hemoglobin, decreases to low	3	0	0	5	3	6	2	1	0	0	0	0	0
Mean Corpuscular Hemoglobin, changes to normal or no changes	18	16	26	28	25	26	12	5	2	8	2	11	7
Mean Corpuscular Hemoglobin, increases to high	1	0	2	3	0	2	2	0	0	0	0	0	0
Mean Corpuscular Volume, decreases to low	1	2	0	5	0	2	0	2	0	1	0	0	0
Mean Corpuscular Volume, changes to normal or no changes	20	11	28	29	28	29	13	4	2	7	2	9	7
Mean Corpuscular Volume, increases to high	1	3	0	3	0	3	3	0	0	0	0	2	0
Erythrocytes, decreases to low	13	7	11	17	12	22	10	2	1	3	2	1	3
Erythrocytes, changes to normal or no changes	9	9	17	19	16	12	5	3	1	5	0	10	4
Erythrocytes, increases to high	0	0	0	0	0	0	1	1	0	0	0	0	1
Hematocrit, decreases to low	11	9	13	18	12	24	10	3	1	6	2	5	4
Hematocrit, changes to normal or no changes	11	7	15	19	16	10	6	3	1	2	0	6	3
Hematocrit, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Hemoglobin, decreases to low	13	8	13	21	11	22	10	3	1	5	2	5	5
Hemoglobin, changes to normal or no changes	9	8	15	16	17	12	6	3	1	3	0	6	2
Hemoglobin, increases to high	0	0	0	0	0	0	0	0	0	0	0	0	0
Leukocytes, decreases to low	11	4	9	15	16	15	8	2	1	5	1	10	1
Leukocytes, changes to normal or no changes	10	8	18	20	9	15	6	3	0	3	1	1	4
Leukocytes, increases to high	3	4	1	2	4	4	4	1	1	1	0	1	2
Lymphocytes, decreases to low	8	6	8	8	11	15	7	1	1	1	0	3	3
Lymphocytes, changes to normal or no changes	14	10	20	29	17	19	9	5	0	7	2	8	4
Lymphocytes, increases to high	0	0	0	0	0	0	0	0	1	0	0	0	0
Monocytes, decreases to low	5	1	3	5	5	6	1	1	1	2	0	2	0
Monocytes, changes to normal or no changes	14	11	20	28	19	20	9	3	0	3	1	4	6
Monocytes, increases to high	4	5	3	4	5	10	6	1	1	2	1	2	1
Neutrophils, decreases to low	8	2	6	12	7	8	5	3	2	4	1	7	1
Neutrophils, changes to normal or no changes	12	11	19	22	18	22	7	2	0	1	1	2	4
Neutrophils, increases to high	2	3	3	3	3	4	4	2	0	4	0	4	2
Platelets, decreases to low	14	13	8	17	20	14	5	3	1	5	1	9	2
Platelets, changes to normal or no changes	6	3	20	18	8	14	10	2	1	3	1	2	4
Platelets, increases to high	3	3	1	2	1	10	2	1	0	0	0	1	1
Reticulocytes, decreases to low	9	12	8	9	15	19	5	2	1	1	0	5	2
Reticulocytes, changes to normal or no changes	8	1	11	13	3	6	4	2	0	3	1	3	3
Reticulocytes, increases to high	10	10	12	15	14	21	11	2	2	4	1	3	2

SecondaryPart 2: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters

Time frame:: Baseline (Day 1) and up to 42 months
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Partial Thromboplastin Time, decreases to low	2	0	3	0	0	1	2	0	1	0	—	0	1
Partial Thromboplastin Time, changes to normal or no changes	3	7	14	19	12	7	8	2	0	1	—	4	3
Partial Thromboplastin Time, increases to high	8	4	2	16	6	12	6	3	1	3	—	5	3
Prothrombin Intl. Normalized Ratio, decreases to low	0	0	0	0	0	1	0	0	0	0	0	0	0
Prothrombin Intl. Normalized Ratio, changes to normal or no changes	17	2	23	24	18	15	8	5	2	8	2	9	6
Prothrombin Intl. Normalized Ratio, increases to high	5	14	5	13	10	18	8	1	0	0	0	2	1
Prothrombin Time, decreases to low	0	0	0	0	0	1	2	1	0	0	0	0	1
Prothrombin Time, changes to normal or no changes	9	5	18	16	14	17	7	2	1	4	2	6	4
Prothrombin Time, increases to high	13	10	8	21	13	17	8	3	1	4	0	5	2

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Occult Blood, No Change or Change to Negative	19	10	20	28	18	20	13	3	2	5	2	3	4
Occult Blood, Change to Positive	3	6	8	9	10	14	3	2	0	3	0	6	3
Protein, No Change or Change to Negative	13	9	15	24	14	17	9	2	0	5	2	4	5
Protein, Change to Positive	9	7	13	13	14	17	7	3	2	3	0	5	2
Ketones, No Change or Change to Negative	17	9	22	27	20	24	9	4	2	8	2	7	4
Ketones, Change to Positive	5	7	6	10	8	10	7	1	0	0	0	2	3
Glucose, No Change or Change to Negative	20	15	24	32	24	34	14	5	2	7	2	9	7
Glucose, Change to Positive	2	1	4	5	4	0	2	0	0	1	0	0	0

SecondaryPart 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
Reported as:: Mean · Potential of Hydrogen (pH)

Part 2: Changes From Baseline in Urine Potential of Hydrogen (pH)
Potential of Hydrogen (pH)	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Baseline	5.95 ± 0.800	6.19 ± 0.772	5.97 ± 0.706	6.35 ± 0.715	6.00 ± 0.707	6.15 ± 0.784	6.36 ± 0.842	5.90 ± 0.224	5.75 ± 0.354	6.25 ± 0.845	5.50 ± 0.000	6.17 ± 0.707	5.43 ± 0.345
CFB to Day 8	0.07 ± 0.795	-0.13 ± 0.694	-0.15 ± 0.525	-0.24 ± 0.760	-0.04 ± 0.693	-0.15 ± 0.892	-0.19 ± 0.693	-0.13 ± 0.250	-0.50 ± NA	-0.21 ± 0.859	0.00 ± 0.000	-0.06 ± 0.464	0.07 ± 0.189
CFB to Day 15	0.17 ± 0.842	-0.16 ± 0.700	0.11 ± 0.706	0.01 ± 0.809	-0.02 ± 0.620	0.03 ± 0.730	0.07 ± 0.842	0.10 ± 0.548	0.25 ± 0.354	-0.25 ± 0.964	0.00 ± 0.707	0.06 ± 0.464	0.00 ± 0.577
CFB to Week 4 Day 1	-0.29 ± 0.902	-0.06 ± 0.704	-0.03 ± 0.899	-0.23 ± 0.741	-0.13 ± 0.837	-0.32 ± 0.793	-0.15 ± 0.966	-0.20 ± 0.447	0.00 ± 0.707	0.00 ± 0.612	0.50 ± 0.707	0.33 ± 0.500	-0.07 ± 0.189
CFB to Week 6 Day 1	0.31 ± 0.727	-0.54 ± 0.594	-0.03 ± 0.591	-0.42 ± 0.767	0.08 ± 0.929	-0.48 ± 0.886	-0.27 ± 0.942	-0.13 ± 0.250	0.50 ± NA	-0.10 ± 0.822	0.50 ± NA	0.14 ± 0.627	0.33 ± 0.606
CFB to Week 8	0.57 ± 1.018	-0.50 ± 0.632	-0.31 ± 0.651	-0.16 ± 0.670	-0.38 ± 0.944	-0.30 ± 0.968	-0.25 ± 0.783	0.13 ± 0.629	0.50 ± NA	0.00 ± 0.935	0.00 ± NA	-0.10 ± 0.822	0.10 ± 0.224
CFB to Week 12	—	0.14 ± 0.988	0.00 ± NA	-0.17 ± 0.931	0.20 ± 0.837	-0.33 ± 1.000	-0.50 ± NA	-1.00 ± NA	—	—	—	0.50 ± NA	0.00 ± NA
CFB to Week 16	-1.00 ± NA	-0.50 ± 0.791	-0.25 ± 0.354	0.23 ± 0.932	0.10 ± 0.568	-0.23 ± 1.032	0.31 ± 0.704	-0.50 ± NA	—	-0.17 ± 0.764	—	—	0.75 ± 1.061
CFB to Week 20	—	0.00 ± 0.816	—	0.25 ± 0.866	-0.50 ± NA	-0.19 ± 0.799	0.50 ± NA	—	—	—	—	—	—
CFB to Week 24	-0.75 ± 0.354	0.00 ± 0.707	0.00 ± NA	0.58 ± 1.201	0.25 ± 0.354	-0.66 ± 1.012	-0.67 ± 0.606	—	—	0.75 ± 1.061	—	0.50 ± NA	0.00 ± 0.000
CFB to Week 28	—	-0.13 ± 0.854	—	1.25 ± 0.354	—	-0.75 ± 1.258	0.25 ± 0.354	—	—	—	—	—	—
CFB to Week 32	-0.50 ± NA	0.00 ± 0.866	—	0.67 ± 0.577	0.25 ± 0.354	-0.62 ± 1.121	-0.25 ± 0.645	0.00	—	0.00 ± NA	—	—	0.00 ± 0.000
CFB to Week 36	-0.50 ± NA	-0.17 ± 0.764	—	—	—	-0.20 ± 0.570	—	—	—	—	—	—	—
CFB to Week 40	-1.00 ± NA	0.25 ± 1.061	—	1.25 ± 1.061	—	-0.54 ± 0.946	-0.13 ± 0.629	—	—	—	—	—	0.00 ± 0.000
CFB to Week 44	-1.50 ± NA	0.00 ± NA	—	—	—	0.50 ± 0.866	0.00 ± NA	—	—	—	—	—	—
CFB to Week 48	—	0.50 ± 1.414	—	1.00 ± 1.414	0.00 ± 0.000	-0.50 ± 1.027	-0.13 ± 0.629	0.00 ± NA	—	—	—	—	0.00 ± 0.000
CFB to Week 52	—	0.00 ± NA	—	—	—	0.38 ± 0.629	0.00 ± NA	—	—	—	—	—	—
CFB to Week 56	—	0.00 ± NA	—	0.00 ± NA	—	-0.20 ± 0.570	0.00 ± 0.000	—	—	—	—	—	0.00 ± NA
CFB to Week 60	—	-0.50 ± NA	—	—	—	0.50 ± 0.707	—	—	—	—	—	—	—
CFB to Week 64	—	—	—	0.00 ± NA	—	-0.50 ± 0.447	-0.50 ± 0.707	—	—	—	—	—	0.00
CFB to Week 68	—	-0.50 ± NA	—	—	—	0.25 ± 0.354	—	—	—	—	—	—	—
CFB to Week 72	—	-0.50 ± NA	—	—	—	-0.50 ± 0.707	0.00 ± 0.000	0.50 ± NA	—	—	—	—	0.00 ± NA
CFB to Week 76	—	-0.50 ± NA	—	—	—	0.50 ± NA	—	—	—	—	—	—	—
CFB to Week 80	—	-0.50 ± NA	—	—	—	-0.38 ± 0.479	0.00 ± NA	0.00 ± NA	—	—	—	—	—
CFB to Week 84	—	-0.50 ± NA	—	—	—	2.00 ± NA	—	—	—	—	—	—	—
CFB to Week 88	—	-0.50 ± NA	—	—	—	-0.30 ± 0.671	0.00 ± NA	—	—	—	—	—	—
CFB to Week 92	—	-1.00 ± NA	—	—	—	1.00 ± NA	—	—	—	—	—	—	—
CFB to Week 96	—	-0.50 ± NA	—	—	—	0.17 ± 1.443	—	0.00 ± NA	—	—	—	—	—
CFB to Week 100	—	-0.50 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 104	—	-0.50 ± NA	—	—	—	-1.25 ± 0.354	—	—	—	—	—	—	—
CFB to Week 108	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 112	—	-0.50 ± NA	—	—	—	—	—	-0.50 ± NA	—	—	—	—	—
CFB to Week 116	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 120	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 124	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 128	—	-0.50 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 132	—	0.50 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 136	—	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	—
CFB to Week 144	—	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—
CFB to Week 152	—	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—
CFB to Week 160	—	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	—
CFB to Week 168	—	—	—	—	—	—	—	-0.50 ± NA	—	—	—	—	—
CFB to Week 176	—	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—
CFB to Week 184	—	—	—	—	—	—	—	0.00 ± NA	—	—	—	—	—

SecondaryPart 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
Reported as:: Mean · Ratio

Part 2: Changes From Baseline in Urine Specific Gravity
Ratio	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Baseline	1.02 ± 0.007	1.02 ± 0.006	1.02 ± 0.007	1.02 ± 0.007	1.02 ± 0.006	1.02 ± 1.02	1.02 ± 0.007	1.02 ± 0.012	1.02 ± 0.004	1.02 ± 0.007	1.03 ± 0.004	1.02 ± 0.007	1.02 ± 0.009
CFB to Day 8	0.00 ± 0.007	0.00 ± 0.008	0.00 ± 0.008	0.00 ± 0.007	0.00 ± 0.006	0.00 ± 0.007	0.00 ± 0.007	0.00 ± 0.003	0.01 ± NA	0.00 ± 0.008	0.00 ± 0.000	0.00 ± 0.00	0.00 ± 0.005
CFB to Day 15	0.00 ± 0.007	0.00 ± 0.006	0.00 ± 0.005	0.00 ± 0.006	0.00 ± 0.006	0.00 ± 0.006	0.00 ± 0.008	0.00 ± 0.006	0.00 ± 0.004	0.00 ± 0.007	0.00 ± 0.000	0.00 ± 0.005	0.00 ± 0.006
CFB to Week 4 Day 1	0.00 ± 0.007	0.00 ± 0.006	0.00 ± 0.006	0.00 ± 0.008	0.00 ± 0.007	0.00 ± 0.008	0.00 ± 0.009	0.00 ± 0.008	0.00 ± 0.000	0.00 ± 0.006	-0.01 ± 0.004	0.00 ± 0.005	0.00 ± 0.006
CFB to Week 6 Day 1	0.00 ± 0.008	0.00 ± 0.005	0.00 ± 0.006	0.00 ± 0.008	0.00 ± 0.008	0.00 ± 0.008	0.00 ± 0.010	0.01 ± 0.004	-0.01 ± NA	0.01 ± 0.005	-0.01 ± NA	0.00 ± 0.004	0.00 ± 0.010
CFB to Week 8	0.00 ± 0.008	0.00 ± 0.006	0.00 ± 0.008	0.00 ± 0.029	0.00 ± 0.007	0.00 ± 0.008	0.00 ± 0.009	0.00 ± 0.011	0.00 ± NA	0.00 ± 0.003	-0.01 ± NA	0.00 ± 0.007	0.01 ± 0.005
CFB to Week 12	—	0.00 ± 0.005	0.00 ± NA	0.00 ± 0.006	0.00 ± 0.011	0.00 ± 0.006	-0.02 ± NA	-0.01 ± NA	—	—	—	0.00 ± NA	0.01 ± NA
CFB to Week 16	0.01 ± NA	0.00 ± 0.008	0.00 ± 0.004	0.00 ± 0.007	0.00 ± 0.006	0.00 ± 0.009	0.01 ± 0.007	0.02 ± NA	—	0.01 ± 0.005	—	—	0.01 ± 0.006
CFB to Week 20	—	0.00 ± 0.005	—	0.00 ± 0.010	0.01 ± NA	0.00 ± 0.009	-0.01 ± NA	—	—	—	—	—	—
CFB to Week 24	0.00 ± 0.002	0.00 ± 0.005	0.00 ± NA	NA ± 0.009	0.01 ± 0.011	0.00 ± 0.011	0.00 ± 0.007	—	—	0.00 ± 0.000	—	-0.01 ± NA	0.00 ± 0.001
CFB to Week 28	—	0.00 ± 0.008	—	-0.01 ± 0.021	—	0.00 ± 0.015	0.00 ± 0.023	—	—	—	—	—	—
CFB to Week 32	0.00 ± NA	0.00 ± 0.005	—	0.00 ± 0.008	0.00 ± 0.000	0.00 ± 0.012	0.00 ± 0.011	0.02 ± NA	—	0.00 ± NA	—	—	0.00 ± 0.007
CFB to Week 36	0.01 ± NA	0.00 ± 0.003	—	—	—	0.01 ± 0.009	—	—	—	—	—	—	—
CFB to Week 40	0.00 ± NA	-0.01 ± 0.007	—	0.00 ± 0.006	—	0.00 ± 0.011	0.01 ± 0.011	—	—	—	—	—	-0.01 ± 0.011
CFB to Week 44	0.01 ± NA	0.00 ± NA	—	—	—	0.00 ± 0.008	0.02 ± NA	—	—	—	—	—	—
CFB to Week 48	—	-0.01 ± 0.000	—	0.01 ± 0.013	0.01 ± 0.011	0.01 ± 0.009	0.01 ± 0.013	0.02 ± NA	—	—	—	—	0.00 ± 0.002
CFB to Week 52	—	-0.01 ± NA	—	—	—	0.00 ± 0.008	0.02 ± NA	—	—	—	—	—	—
CFB to Week 56	—	-0.01 ± NA	—	-0.01 ± NA	—	-0.01 ± 0.005	0.01 ± 0.009	—	—	—	—	—	0.01 ± NA
CFB to Week 60	—	-0.01 ± NA	—	—	—	-0.01 ± 0.001	—	—	—	—	—	—	—
CFB to Week 64	—	—	—	0.01 ± NA	—	0.00 ± 0.009	0.00 ± 0.011	—	—	—	—	—	0.01 ± NA
CFB to Week 68	—	-0.01 ± NA	—	—	—	-0.01 ± 0.002	—	—	—	—	—	—	—
CFB to Week 72	—	-0.01 ± NA	—	—	—	0.00 ± 0.005	0.00 ± 0.001	0.01 ± NA	—	—	—	—	0.00 ± NA
CFB to Week 76	—	-0.01 ± NA	—	—	—	-0.01 ± NA	—	—	—	—	—	—	—
CFB to Week 80	—	-0.01 ± NA	—	—	—	0.00 ± 0.004	0.00 ± NA	0.02 ± NA	—	—	—	—	—
CFB to Week 84	—	0.00 ± NA	—	—	—	-0.01 ± NA	—	—	—	—	—	—	—
CFB to Week 88	—	-0.01 ± NA	—	—	—	0.00 ± 0.005	0.01 ± NA	—	—	—	—	—	—
CFB to Week 92	—	0.00 ± NA	—	—	—	-0.01 ± NA	—	—	—	—	—	—	—
CFB to Week 96	—	-0.01 ± NA	—	—	—	0.00 ± 0.017	—	0.02 ± NA	—	—	—	—	—
CFB to Week 100	—	-0.01 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 104	—	-0.01 ± NA	—	—	—	0.00 ± 0.004	—	—	—	—	—	—	—
CFB to Week 108	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 112	—	-0.01 ± NA	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 116	—	-0.01 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 120	—	-0.01 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 124	—	-0.01 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 128	—	-0.01 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 132	—	0.00 ± NA	—	—	—	—	—	—	—	—	—	—	—
CFB to Week 136	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 144	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 152	—	—	—	—	—	—	—	0.01 ± NA	—	—	—	—	—
CFB to Week 160	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 168	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 176	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—
CFB to Week 184	—	—	—	—	—	—	—	0.02 ± NA	—	—	—	—	—

SecondaryPart 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
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Maximum Grade Worst Case Increase Post-baseline Relative to Baseline in Vital Signs
Participants	Part 2: GSK3326595 400mg (TNBC)	Part 2: GSK3326595 400mg (mTCC)	Part 2: GSK3326595 400mg (GBM)	Part 2: GSK3326595 400mg (ER+BC)	Part 2: GSK3326595 400mg (HPV+)	Part 2: GSK3326595 400mg (ACC)	Part 2: GSK3326595 300mg (ACC)	Part 2: GSK3326595 400mg (NHL P53 Mutant)	Part 2: GSK3326595 300mg (NHL P53 Mutant)	Part 2: GSK3326595 400mg (NHL P53 Wild Type)	Part 2: GSK3326595 300mg (NHL P53 Wild Type)	Part 2: GSK3326595 400mg (NHL P53 Unknown)	Part 2: GSK3326595 300mg (NSCLC)
Heart Rate, changes to low	0	3	2	3	2	6	3	0	0	1	0	2	0
Heart Rate, changes to normal or no changes	14	5	25	19	17	21	7	4	1	6	2	7	5
Heart Rate, changes to high	8	9	1	16	9	8	6	2	1	1	0	3	2
Temperature, changes to low	0	0	0	1	0	0	0	1	0	0	0	0	0
Temperature, changes to normal or no changes	21	14	28	36	25	31	16	4	2	8	2	10	7
Temperature, changes to high	1	2	0	0	3	3	0	1	0	0	0	1	0
Systolic Blood Pressure, changes to low	4	3	0	1	2	2	2	0	0	0	0	0	1
Systolic Blood Pressure, changes to normal or no changes	14	7	20	28	21	23	12	5	1	7	2	8	4
Systolic Blood Pressure, changes to high	5	6	8	9	5	9	2	1	1	1	0	3	2
Diastolic Blood Pressure, changes to low	7	6	2	16	5	10	6	3	0	3	0	3	2
Diastolic Blood Pressure, changes to normal or no changes	10	6	20	15	18	16	7	2	1	3	1	6	4
Diastolic Blood Pressure, changes to high	8	4	6	11	6	11	4	3	1	2	1	3	1

SecondaryPart 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595