Last updated: 10/08/2025 08:00:16

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 lymphomaMeteor 1

GSK study ID
204653
See study documents
Clinicaltrials.gov ID
NCT02783300
See results summary
EudraCT ID
2016-000278-39
EU CT Number
Not applicable
Trial status
Other
Other
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: 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).
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
None (Open Label)
Allocation:
Non-randomized
Primary outcomes:

Parts 1 and 3: Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions

Timeframe: Up to approximately 2 years

Part 1: Number of participants with dose limiting toxicities (DLTs)

Timeframe: Up to 21 days

Parts 1 and 3: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters.

Timeframe: Up to approximately 2 years

Part 2: Participants with solid tumors (non-GBM): Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1

Timeframe: Up to approximately 2 years

Part 2: Participants with NHL: ORR based on Lugano criteria

Timeframe: Up to approximately 2 years

Part 2: GBM cohort: Six-month progression free survival (PFS) rate

Timeframe: Up to 6 months

Secondary outcomes:

Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595

Timeframe: Baseline and up to approximately 2 years

Parts 1 and 3: Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: AUC over the dosing interval tau (AUC[0-tau]) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: Terminal phase half-life (t1/2) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: Oral clearance (CL/F) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: Accumulation ratio (AR) of GSK3326595

Timeframe: Up to approximately 2 years

Parts 1 and 3: Time invariance (TI) of GSK3326595

Timeframe: Up to approximately 2 years

Part 1: Participants with solid tumors: Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1

Timeframe: Up to approximately 2 years

Part 3: ORR based on immune-based RECIST (iRECIST) criteria

Timeframe: Up to approximately 2 years

Part 2: PFS

Timeframe: Up to approximately 2 years

Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria

Timeframe: Up to approximately 2 years

Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR)

Timeframe: Up to approximately 2 years

Part 2: (Participants in ACC tablet cohort): Overall survival (OS)

Timeframe: Up to approximately 2 years

Part 2: Number of participants with any AEs, SAEs, withdrawal due to AEs, dose reductions or delays

Timeframe: Up to approximately 2 years

Part 2: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters

Timeframe: Up to approximately 2 years

Interventions:
  • Drug: GSK3326595
  • Drug: Pembrolizumab
    • Enrollment:
    288
    Primary completion date:
    2023-30-08
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    M M Gounder, P Martin-Romano, A Italiano, L L Siu, P A Cassier, G S Falchook, I S Lossos, D W Rasco, J F Hilton, M A McKean, F L Opdam, J Strauss, M De Jonge, J S P Vermaat, T Crossman, M Zajac, A Tarkar, F Gonzalez Carreras, B E Kremer, O Barbash, S Segal, R Parasrampuria, S Postel-Vinay. Phase 1b and Dose-Expansion Study of GSK3326595, a PRMT5 Inhibitor as Monotherapy and in Combination With Pembrolizumab in Patients With Advanced Cancers. Annals of oncology : official journal of the European Society for Medical Oncology. 2025-Sep-09; doi:10.1016/j.annonc.2025.08.3757 http://dx.doi.org/S0923-7534(25)04696-410.1016/j.annonc.2025.08.3757 PMID: 40935292 DOI: 10.1016/j.annonc.2025.08.3757
    Medical condition
    Neoplasms
    Product
    GSK3326595
    Collaborators
    NA
    Study date(s)
    August 2016 to August 2023
    Type
    Interventional
    Phase
    1

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Inclusion criteria:
    • Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained)
    Inclusion and exclusion criteria
    Inclusion 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.

    Trial location(s)

    Location
    Status
    Contact us
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    Location
    GSK Investigational Site
    AMSTERDAM, Netherlands, 1066 CX
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Dallas, TX, United States, 75230
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Lyon Cedex 08, France, 69373
    Status
    Study Complete
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    Location
    GSK Investigational Site
    Miami, FL, United States, 33136
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    San Antonio, TX, United States, 78229
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Toronto, ON, Canada, M5G 1Z5
    Status
    Study Complete
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    Showing 1 - 6 of 15 Results

    Study documents

    Protocol
    Available language(s): English
    Download document(s)
    Statistical analysis plan
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Other
    Actual primary completion date
    2023-30-08
    Actual study completion date
    2023-30-08

    Plain language summaries

    Summary of results in plain language
    Available language(s): English, Dutch, French
    Download document(s)

    To view plain language summaries on trialsummaries.com click here.

    Additional information about the trial

    Additional information
    Not applicable
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