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 (Meteor 1)

February 15, 2025 updated by: GlaxoSmithKline

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

This first time in human (FTIH) open-label, dose escalation study will assess the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of GSK3326595 in participants with advanced or recurrent solid tumors, as well as clinical activity in participants with a subset of solid tumors and non-Hodgkin's lymphoma (NHL).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
297

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • GSK Investigational Site
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • GSK Investigational Site
      • Toronto, Ontario, Canada, M5G 1Z5
        • GSK Investigational Site
  • France
      • Bordeaux, France, 33076
        • GSK Investigational Site
      • Lyon Cedex 08, France, 69373
        • GSK Investigational Site
      • Villejuif cedex, France, 94805
        • GSK Investigational Site
  • Netherlands
      • Amsterdam, Netherlands, 1066 CX
        • GSK Investigational Site
      • Leiden, Netherlands, 2333 ZA
        • GSK Investigational Site
      • Rotterdam, Netherlands, 3015 GD
        • GSK Investigational Site
  • United States
    • Colorado
      • Denver, Colorado, United States, 80218
        • GSK Investigational Site
    • Florida
      • Miami, Florida, United States, 33136
        • GSK Investigational Site
    • New York
      • New York, New York, United States, 10065
        • GSK Investigational Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • GSK Investigational Site
    • Texas
      • Dallas, Texas, United States, 75230
        • GSK Investigational Site
      • San Antonio, Texas, United States, 78229
        • GSK Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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:

  • 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
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
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
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
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
Drug: Pembrolizumab
Pembrolizumab will be administered.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part 1: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 30 months
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).
Up to 30 months
Part 1: Number of Participants Withdrawn Due to AEs
Time Frame: Up to 30 months
The data for number of participants withdrawn due to AEs have been presented.
Up to 30 months
Part 1: Number of Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Up to 21 days
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.
Up to 21 days
Part 1: Number of Participants With Dose Modifications of GSK3326595
Time Frame: Up to 30 months
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Time Frame: Baseline (Day 1) and up to 30 months
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%.
Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Time Frame: Baseline (Day 1) and up to 30 months
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%.
Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Time Frame: Baseline (Day 1) and up to 30 months
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%.
Baseline (Day 1) and up to 30 months
Part 1: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Time Frame: Baseline (Day 1) and up to 30 months
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.
Baseline (Day 1) and up to 30 months
Part 1: Changes From Baseline in Urine Potential of Hydrogen (pH)
Time Frame: Baseline (Day 1) and up to week 132
Urine samples were collected from participants to assess urine pH levels.
Baseline (Day 1) and up to week 132
Part 1: Changes From Baseline in Urine Specific Gravity
Time Frame: Baseline (Day 1) and up to week 132
Urine samples were collected from participants to assess urine specific gravity.
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
Time Frame: Baseline (Day 1) and up to 30 months
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%.
Baseline (Day 1) and up to 30 months
Part 3: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 10 months
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.
Up to 10 months
Part 3: Number of Participants Withdrawn Due to AEs
Time Frame: Up to 10 months
The data for number of participants withdrawn due to AEs have been presented.
Up to 10 months
Part 3: Number of Participants With Dose Modifications of GSK3326595 and Pembrolizumab
Time Frame: Up to 10 months
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 and pembrolizumab have been presented.
Up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Time Frame: Baseline (Day 1) and up to 10 months
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.
Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Time Frame: Baseline (Day 1) and up to 10 months
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.
Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Time Frame: Baseline (Day 1) and up to 10 months
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.
Baseline (Day 1) and up to 10 months
Part 3: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Time Frame: Baseline (Day 1) and up to 10 months
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.
Baseline (Day 1) and up to 10 months
Part 3: Changes From Baseline in Urine Potential of Hydrogen (pH)
Time Frame: Baseline (Day 1) and up to Week 42
Urine samples were collected from participants to assess urine pH levels.
Baseline (Day 1) and up to Week 42
Part 3: Changes From Baseline in Urine Specific Gravity
Time Frame: Baseline (Day 1) and up to Week 42
Urine samples were collected from participants to assess urine specific gravity.
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
Time Frame: Baseline (Day 1) and up to 10 months
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%.
Baseline (Day 1) and up to 10 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part 2: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to 42 months
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.
Up to 42 months
Part 2: Number of Participants Withdrawn Due to AEs
Time Frame: Up to 42 months
The data for number of participants withdrawn due to AEs have been presented.
Up to 42 months
Part 2: Number of Participants With Dose Modifications of GSK3326595
Time Frame: Up to 42 months
The number of participants who had any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Time Frame: Baseline (Day 1) and up to 42 months
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%.
Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Time Frame: Baseline (Day 1) and up to 42 months
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%.
Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Time Frame: Baseline (Day 1) and up to 42 months
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%.
Baseline (Day 1) and up to 42 months
Part 2: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Time Frame: Baseline (Day 1) and up to 42 months
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.
Baseline (Day 1) and up to 42 months
Part 2: Changes From Baseline in Urine Potential of Hydrogen (pH)
Time Frame: Baseline (Day 1) and up to week 184
Urine samples were collected from participants to assess urine pH levels.
Baseline (Day 1) and up to week 184
Part 2: Changes From Baseline in Urine Specific Gravity
Time Frame: Baseline (Day 1) and up to week 184
Urine samples were collected from participants to assess urine specific gravity.
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
Time Frame: Baseline (Day 1) and up to 42 months
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%.
Baseline (Day 1) and up to 42 months
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3326595
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
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
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
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
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
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
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
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595. PK parameter was determined using standard non-compartmental methods.
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
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
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3326595
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
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
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.
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
Time Frame: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24h post-dose
Blood samples were collected for pharmacokinetic (PK) analysis of GSK3326595.
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
Time Frame: Up to 30 months
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.
Up to 30 months
Part 2: Overall Response Rate (ORR) (Non-glioblastoma Multiforme [GBM] Cohorts)
Time Frame: Up to 42 months
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).
Up to 42 months
Part 2: Six-month Progression Free Survival (PFS) Rate (GBM Cohort)
Time Frame: At month 6
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).
At month 6
Part 2: Duration of Response (DOR) (ACC Tablet Cohort)
Time Frame: Up to 42 months
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.
Up to 42 months
Part 3: ORR Based on Immune-based RECIST (iRECIST) Criteria
Time Frame: Up to 10 months
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.
Up to 10 months
Part 2: ORR (GBM Cohort) Based on Response Assessment Neuro-Oncology (RANO) Working Group Criteria
Time Frame: Up to 42 months
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.
Up to 42 months
Part 2: ORR (Non-Hodgkin's Lymphoma (NHL) Cohorts) Based on Lugano Criteria
Time Frame: Up to 42 months
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.
Up to 42 months
Part 2: Overall Survival (OS) (ACC Tablet Cohort)
Time Frame: Up to 42 months
Overall survival (OS) was defined as time from first dose until death from any cause in ACC participants who are systemic-treatment naïve.
Up to 42 months
Part 2: Progression-free Survival
Time Frame: Up to 42 months
PFS was defined as time from first dose until radiographic progression per standard criteria or death due to any cause, whichever is earlier.
Up to 42 months
RP2D Phase: Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Up to maximum 42 months
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.
Up to maximum 42 months
RP2D Phase: Number of Participants Withdrawn Due to AEs
Time Frame: Up to maximum 42 months
The data for number of participants withdrawn due to AEs have been presented.
Up to maximum 42 months
RP2D Phase: Number of Participants With Dose Modifications of GSK3326595
Time Frame: Up to maximum 42 months
The number of participants who experienced any dose modifications (interruptions and reductions) of GSK3326595 have been presented.
Up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Clinical Chemistry Parameters
Time Frame: Baseline (Day 1) and up to maximum 42 months
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%.
Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Hematology Parameters
Time Frame: Baseline (Day 1) and up to maximum 42 months
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%.
Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Coagulation Parameters
Time Frame: Baseline (Day 1) and up to maximum 42 months
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%.
Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Number of Participants With Worst Case Change From Baseline in Urinalysis Parameters
Time Frame: Baseline (Day 1) and up to maximum 42 months
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.
Baseline (Day 1) and up to maximum 42 months
RP2D Phase: Changes From Baseline in Urine Potential of Hydrogen (pH)
Time Frame: Baseline (Day 1) and up to Week 184
Urine samples were collected from participants to assess urine pH levels.
Baseline (Day 1) and up to Week 184
RP2D Phase: Changes From Baseline in Urine Specific Gravity
Time Frame: Baseline (Day 1) and up to Week 184
Urine samples were collected from participants to assess urine specific gravity.
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
Time Frame: Baseline (Day 1) and up to maximum 42 months
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%.
Baseline (Day 1) and up to maximum 42 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 30, 2023

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 11, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 23, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 26, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 15, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 204653
  • 2016-000278-39 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.

IPD Sharing Access Criteria

Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings