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OpenTrials
Completed

NCT Number: NCT02783300

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

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).

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Key information

Conditions

Neoplasms Adenocarcinoma Bronchial Neoplasms Carcinoma Carcinoma, Adenoid Cystic Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Carcinoma, Squamous Cell Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Head and Neck Neoplasms Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lung Diseases Lung Neoplasms Lymphatic Diseases Lymphoma Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Male Urogenital Diseases Melanoma Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Squamous Cell Carcinoma of Head and Neck Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site, Edmonton, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GSK3326595

Drug

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

Pembrolizumab

Drug

Pembrolizumab will be administered.

Primary outcomes

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. 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%.

  6. 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%.

  7. 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%.

  8. 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.

  9. 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.

  10. 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.

  11. 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%.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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%.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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%.

  5. 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%.

  6. 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%.

  7. 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.

  8. 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.

  9. 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.

  10. 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%.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  21. 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.

  22. 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.

  23. 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

  24. 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

  25. 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.

  26. 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.

  27. 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.

  28. 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).

  29. 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).

  30. 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.

  31. 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.

  32. 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.

  33. 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.

  34. 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.

  35. 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.

  36. 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.

  37. 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.

  38. 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.

  39. 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%.

  40. 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%.

  41. 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%.

  42. 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.

  43. 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.

  44. 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.

  45. 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%.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study title

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

Acronym: Meteor 1

Important dates

Study start
2016
Primary completion
2023
Study completion
2023
First posted
May 26, 2016
Registry last updated
Mar 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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