Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02783300
Recruitment Status : Recruiting
First Posted : May 26, 2016
Last Update Posted : May 17, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE April 11, 2016
First Posted Date  ICMJE May 26, 2016
Last Update Posted Date May 17, 2021
Actual Study Start Date  ICMJE August 30, 2016
Estimated Primary Completion Date April 29, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 13, 2021)
  • Parts 1 and 3: Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions [ Time Frame: Up to approximately 2 years ]
    All AEs, SAEs and dose modifications will be collected.
  • Part 1: Number of participants with dose limiting toxicities (DLTs) [ Time Frame: Up to 21 days ]
    An event is considered to be a DLT if the event occurs within the first 21 days of treatment and meets the dose-limiting toxicity criteria, unless it can be clearly established that the event is unrelated to treatment.
  • Parts 1 and 3: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters. [ Time Frame: Up to approximately 2 years ]
    Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points.
  • Part 2: Participants with solid tumors (non-GBM): Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1 [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. ACC tablet cohort will score ORR by independent central review, all other non-GBM solid tumor cohorts will score ORR by investigator assessment.
  • Part 2: Participants with NHL: ORR based on Lugano criteria [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.
  • Part 2: GBM cohort: Six-month progression free survival (PFS) rate [ Time Frame: Up to 6 months ]
    PFS is 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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 23, 2016)
  • Part 1: Number of subjects with any adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
    AEs and SAEs will be collected from the start of study treatment until 30 days after the last dose of study treatment
  • Part 1: Number of subjects withdrawn due to AEs, with dose interruptions and with dose reductions. [ Time Frame: Up to 2 years ]
  • Part 1: Dose limiting toxicity (DLT) [ Time Frame: Up to 2 years ]
    An event is considered to be a dose-limiting toxicity (DLT) if the event is attributed (definitely, probably or possibly) to the study treatment during the first 21 days of treatment.
  • Part 1: Changes from Baseline in hematology laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in clinical chemistry laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in urinalysis laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in temperature [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in systolic and diastolic blood pressure [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in pulse rate [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in respiratory rate [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline performance status assessment is based on the Eastern cooperative oncology group (ECOG) scale [ Time Frame: Baseline and up to 2 years ]
    Eastern Cooperative Oncology Group (ECOG) scale rating from 0 to 5
  • Part 1: Changes from Baseline in Electrocardiogram (ECG) parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in Echocardiogram (ECHO) parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in Troponin [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Solid tumor cohorts: Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR is defined as the percentage of subjects achieving a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1
  • Part 2: Glioblastoma multiforme (GBM) cohort: Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR is defined as CR or PR and is based on Response Assessment in Neuro-Oncology (RANO) Working Group criteria
  • Part 2: Non-Hodgkin's lymphoma (NHL) cohort(s): Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR is defined as the percentage of subjects achieving CR or PR based on International Workshop criteria
  • Part 1: Changes from Baseline in physical examinations parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Changes from Baseline in organ-specific parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 1: Number of pregnancies reported during study period [ Time Frame: Up to 2 years ]
    Details of all pregnancies in female subjects and female partners of male subjects will be collected.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2021)
  • Parts 1, 2 and 3: Change from Baseline in symmetrical arginine dimethylation (SDMA) as a PD measure [ Time Frame: Baseline and up to approximately 2 years ]
    Evaluation of change from baseline in SDMA, a PD biomarker of PRMT5 inhibition.
  • Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595 [ Time Frame: Baseline and up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the Cmax of GSK3326595.
  • Parts 1 and 3: Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the AUC (0-inf) of GSK3326595.
  • Parts 1 and 3: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the AUC (0-t) of GSK3326595.
  • Parts 1 and 3: AUC over the dosing interval tau (AUC[0-tau]) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the AUC (0-tau) of GSK3326595.
  • Parts 1 and 3: Terminal phase half-life (t1/2) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the half-life of GSK3326595.
  • Parts 1 and 3: Oral clearance (CL/F) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the CL/F of GSK3326595.
  • Parts 1 and 3: Accumulation ratio (AR) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the AR of GSK3326595.
  • Parts 1 and 3: Time invariance (TI) of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected at given time points to determine the TI of GSK3326595.
  • Parts 1 and 2 (Participants with ACC only) ORR based on RECIST 1.1 criteria [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RANO working group criteria.
  • Part 3: ORR based on immune-based RECIST (iRECIST) criteria [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants achieving confirmed CR or confirmed PR based on immune-based RECIST (iRECIST) criteria.
  • Part 2: PFS [ Time Frame: Up to approximately 2 years ]
    Progression-free survival (PFS) is defined as the time from first dose until radiographic progression per standard criteria or death due to any cause, whichever is earlier.
  • Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria [ Time Frame: Up to approximately 2 years ]
    ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RANO working group criteria.
  • Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR) [ Time Frame: Up to approximately 2 years ]
    DOR is defined as the 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 ICR.
  • Part 2: (Participants in ACC tablet cohort): Overall survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from first dose until death from any cause.
  • Part 2: Number of participants with any AEs, SAEs, withdrawal due to AEs, dose reductions or delays [ Time Frame: Up to approximately 2 years ]
    All AEs, SAEs and dose modifications will be collected.
  • Part 2: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters [ Time Frame: Up to approximately 2 years ]
    Blood and urine samples will be collected for analysis of lab parameters. Vital signs, physical examinations and organ-specific parameters will be collected at specified time points.
  • Part 2: ORR relative to p53 mutational status in participants with NHL [ Time Frame: Up to approximately 2 years ]
    P53 mutational status is collected for participants with NHL to determine the relationship between p53 status and ORR.
  • Part 2: AUC of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected to determine AUC of GSK3326595.
  • Part 2: Cmax of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected to determine Cmax of GSK3326595.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2016)
  • Part 1: Composite of PD data [ Time Frame: Baseline and 2 years ]
    Evaluation of change from baseline in symmetrical arginine dimethylation (SDMA), a pharmacodynamic biomarker of PRMT5 inhibition.
  • Part 1: Maximum observed plasma concentration (Cmax) in plasma following single dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Cmax in plasma following repeat-dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Time to Cmax (tmax) following single dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: tmax following repeat-dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Terminal phase half-life (t½) following single dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: t½ following repeat-dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Area under the plasma concentration-time curve (AUC) following single dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: AUC following repeat-dose administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Oral clearance (CL/F) following administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Time invariance (TI) following administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 1: Accumulation ratio (AR) following administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 2: Progression Free Survival (PFS) to describe the duration of response to GSK3326595 [ Time Frame: Up to 2 years ]
    PFS defined as time from first dose until radiographic progression as measured by standard measures and defined by standard criteria
  • Part 2: Relationship between p53 mutational status and clinical response in subjects with NHL [ Time Frame: Up to 2 years ]
    Tumor biopsies will be performed to obtain p53 gene data.
  • Part 2: Cmax, dose concentration following administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 2: AUC following administration of GSK3326595 [ Time Frame: Up to 2 years ]
  • Part 2: Number of subjects with any AEs and SAEs [ Time Frame: Up to 2 years ]
    AEs and SAEs will be collected from the start of study treatment until 30 days after the last dose of study treatment
  • Part 2: Number of subjects withdrawn due to AEs, with dose interruptions and with dose reductions [ Time Frame: Up to 2 years ]
  • Part 2: Dose limiting toxicity (DLT) [ Time Frame: Up to 2 years ]
    An event is considered to be a dose-limiting toxicity (DLT) if the event meets at least one of the pre-defined toxicity criteria and is attributed as related to the study treatment during the first 21 days of treatment.
  • Part 2: Changes from Baseline in hematology laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in clinical chemistry laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in urinalysis laboratory parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in temperature [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in systolic and diastolic blood pressure [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in pulse rate [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in respiratory rate [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in performance status assessment based on the Eastern Cooperative Oncology Group (ECOG) scale [ Time Frame: Baseline and up to 2 years ]
    Eastern Cooperative Oncology Group (ECOG) scale rating from 0 to 5.
  • Part 2: Changes from Baseline in ECG parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in Echocardiogram (ECHO) parameters [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in Troponin [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Number of pregnancies reported during study period [ Time Frame: Up to 2 years ]
    Details of all pregnancies in female subjects and female partners of male subjects will be collected.
  • Part 1: Disease control rate (DCR) based on RECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    DCR is defined as complete response ([CR)] + partial response ([PR)] + stable disease ([SD]).
  • Part 1: Overall Response Rate (ORR), based on RECIST 1.1 criteria [ Time Frame: Up to 2 years ]
    ORR is defined as CR + PR.
  • Part 2: Change from baseline in SDMA [ Time Frame: Up to 2 years ]
    Pharmacodynamic response assessed by change from baseline in symmetrical arginine dimethylation (SDMA).
  • Part 2: Changes from Baseline in physical examinations [ Time Frame: Baseline and up to 2 years ]
  • Part 2: Changes from Baseline in organ-specific parameters [ Time Frame: Baseline and up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
Brief 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).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
This will be a three-part study where Part 1 is dose escalation, including assessment of Food Effect and Relative Bioavailability, Part 2 is disease specific expansion cohorts to better characterize the clinical activity and safety profile of GSK3326595 and Part 3 is dose determination of GSK3326595 in combination with pembrolizumab.
Masking: None (Open Label)
Masking Description:
This is an open label study.
Primary Purpose: Treatment
Condition  ICMJE Neoplasms
Intervention  ICMJE
  • Drug: GSK3326595
    GSK3326595 will be administered with and without food, in tablet and capsule formulation.
  • Drug: Pembrolizumab
    Pembrolizumab will be administered.
Study Arms  ICMJE
  • 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).
    Intervention: 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.
    Intervention: 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.
    Interventions:
    • Drug: GSK3326595
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 13, 2021)
322
Original Estimated Enrollment  ICMJE
 (submitted: May 23, 2016)
208
Estimated Study Completion Date  ICMJE April 29, 2025
Estimated Primary Completion Date April 29, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com
Listed Location Countries  ICMJE Canada,   France,   Netherlands,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02783300
Other Study ID Numbers  ICMJE 204653
2016-000278-39 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
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.
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.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP