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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)

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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

Study Description
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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).

Condition or disease Intervention/treatment Phase
Neoplasms Drug: GSK3326595 Drug: Pembrolizumab Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 322 participants
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
Official 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
Actual Study Start Date : August 30, 2016
Estimated Primary Completion Date : April 29, 2025
Estimated Study Completion Date : April 29, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
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.


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Part 2: AUC of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected to determine AUC of GSK3326595.

  20. Part 2: Cmax of GSK3326595 [ Time Frame: Up to approximately 2 years ]
    Blood samples will be collected to determine Cmax of GSK3326595.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02783300


Contacts
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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

Locations
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United States, Colorado
GSK Investigational Site Recruiting
Denver, Colorado, United States, 80218
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Gerald Falchook         
United States, Florida
GSK Investigational Site Recruiting
Miami, Florida, United States, 33136
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Izidore S Lossos         
United States, New Jersey
GSK Investigational Site Recruiting
Middletown, New Jersey, United States, 07748
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Mrinal M. Gounder         
United States, New York
GSK Investigational Site Recruiting
Harrison, New York, United States, 10604
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Mrinal M. Gounder         
GSK Investigational Site Recruiting
New York, New York, United States, 10065
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Mrinal M. Gounder         
United States, Tennessee
GSK Investigational Site Recruiting
Nashville, Tennessee, United States, 37203
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Meredith Ann McKean         
United States, Texas
GSK Investigational Site Recruiting
Dallas, Texas, United States, 75230
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: James Strauss         
GSK Investigational Site Recruiting
San Antonio, Texas, United States, 78229
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Drew W Rasco         
Canada, Alberta
GSK Investigational Site Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Quincy Chu         
Canada, Ontario
GSK Investigational Site Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: John Hilton         
GSK Investigational Site Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Lillian Siu         
France
GSK Investigational Site Recruiting
Bordeaux Cedex, France, 33076
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Antoine Italiano         
GSK Investigational Site Recruiting
Lyon Cedex 08, France, 69373
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Philippe Cassier         
GSK Investigational Site Recruiting
Villejuif cedex, France, 94805
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Patricia Martin         
Netherlands
GSK Investigational Site Recruiting
Amsterdam, Netherlands, 1066 CX
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Frans L. Opdam         
GSK Investigational Site Recruiting
Leiden, Netherlands, 2333 ZA
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Joost S.P. Vermaat         
GSK Investigational Site Recruiting
Rotterdam, Netherlands, 3015 GD
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Centre    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Principal Investigator: Maja J.A. de Jonge         
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02783300    
Other Study ID Numbers: 204653
2016-000278-39 ( EudraCT Number )
First Posted: May 26, 2016    Key Record Dates
Last Update Posted: May 17, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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
Keywords provided by GlaxoSmithKline:
GSK3326595
Solid tumor
Non-Hodgkin's lymphoma (NHL)
Urinary tract cancer
Dose escalation
 Adenoid cystic carcinoma (ACC)
Non small-cell lung cancer (NSCLC)
Squamous cell carcinoma of the head and neck (HNSCC)
Melanoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
 Immunoproliferative Disorders
Immune System Diseases
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents