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

Neoplasms Clinical Trial

— Meteor 1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02783300
• Other study ID #: 204653
• Secondary ID: 2016-000278-39
• Status: Completed
• Phase: Phase 1
• Start date: August 30, 2016
• Est. completion date: August 30, 2023

Study information

• Verified date: December 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 288
• Est. completion date: August 30, 2023
• Est. primary completion date: August 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Neoplasms

Intervention

Drug:
• GSK3326595
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
• Pembrolizumab
Pembrolizumab will be administered.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Ottawa	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Lyon Cedex 08
France	GSK Investigational Site	Villejuif cedex
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Leiden
Netherlands	GSK Investigational Site	Rotterdam
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Harrison	New York
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Middletown	New Jersey
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Canada,  France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Parts 1 and 3: Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions	All AEs, SAEs and dose modifications will be collected.	Up to approximately 2 years
Primary	Part 1: Number of participants with dose limiting toxicities (DLTs)	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.	Up to 21 days
Primary	Parts 1 and 3: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters.	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.	Up to approximately 2 years
Primary	Part 2: Participants with solid tumors (non-GBM): Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1	ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.	Up to approximately 2 years
Primary	Part 2: Participants with NHL: ORR based on Lugano criteria	ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.	Up to approximately 2 years
Primary	Part 2: GBM cohort: Six-month progression free survival (PFS) rate	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.	Up to 6 months
Secondary	Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595	Blood samples will be collected at given time points to determine the Cmax of GSK3326595.	Baseline and up to approximately 2 years
Secondary	Parts 1 and 3: Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of GSK3326595	Blood samples will be collected at given time points to determine the AUC (0-inf) of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3326595	Blood samples will be collected at given time points to determine the AUC (0-t) of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: AUC over the dosing interval tau (AUC[0-tau]) of GSK3326595	Blood samples will be collected at given time points to determine the AUC (0-tau) of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: Terminal phase half-life (t1/2) of GSK3326595	Blood samples will be collected at given time points to determine the half-life of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: Oral clearance (CL/F) of GSK3326595	Blood samples will be collected at given time points to determine the CL/F of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: Accumulation ratio (AR) of GSK3326595	Blood samples will be collected at given time points to determine the AR of GSK3326595.	Up to approximately 2 years
Secondary	Parts 1 and 3: Time invariance (TI) of GSK3326595	Blood samples will be collected at given time points to determine the TI of GSK3326595.	Up to approximately 2 years
Secondary	Part 1: Participants with solid tumors: Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1	ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.	Up to approximately 2 years
Secondary	Part 3: ORR based on immune-based RECIST (iRECIST) criteria	ORR is defined as the percentage of participants achieving confirmed CR or confirmed PR based on immune-based RECIST (iRECIST) criteria.	Up to approximately 2 years
Secondary	Part 2: PFS	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.	Up to approximately 2 years
Secondary	Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria	ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RANO working group criteria.	Up to approximately 2 years
Secondary	Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR)	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 Investigator Assessment.	Up to approximately 2 years
Secondary	Part 2: (Participants in ACC tablet cohort): Overall survival (OS)	OS is defined as the time from first dose until death from any cause.	Up to approximately 2 years
Secondary	Part 2: Number of participants with any AEs, SAEs, withdrawal due to AEs, dose reductions or delays	All AEs, SAEs and dose modifications will be collected.	Up to approximately 2 years
Secondary	Part 2: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters	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.	Up to approximately 2 years