Last updated: 11/28/2025 06:31:09
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
EudraCT ID
EU CT Number
Not applicable
Trial status
Terminated (halted prematurely)
Terminated (halted prematurely)
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:
297
Observational study model:
Not applicable
Primary completion date:
2023-30-08
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
- 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
- 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)
Inclusion and exclusion 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)
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Terminated (halted prematurely)
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
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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