Back to resultsAn 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)
Primary Purpose
Neoplasms
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
GSK3326595
Pembrolizumab
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms focused on measuring 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
Eligibility 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.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet
Part 2: Disease-Specific Expansion cohort
Part 3: GSK3326595 in combination with pembrolizumab
Arm Description
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).
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.
Participants with selected solid tumors will be administered GSK3326595 in combination with pembrolizumab as part of this dose determination study.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Parts 1 and 3: Accumulation ratio (AR) of GSK3326595
Blood samples will be collected at given time points to determine the AR of GSK3326595.
Parts 1 and 3: Time invariance (TI) of GSK3326595
Blood samples will be collected at given time points to determine the TI of GSK3326595.
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.
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.
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.
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.
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.
Part 2: (Participants in ACC tablet cohort): Overall survival (OS)
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
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02783300
Brief Title
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
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 30, 2016 (Actual)
Primary Completion Date
August 31, 2023 (Anticipated)
Study Completion Date
August 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
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.
Allocation
Non-Randomized
Enrollment
288 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet
Arm Type
Experimental
Arm Description
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).
Arm Title
Part 2: Disease-Specific Expansion cohort
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 3: GSK3326595 in combination with pembrolizumab
Arm Type
Experimental
Arm Description
Participants with selected solid tumors will be administered GSK3326595 in combination with pembrolizumab as part of this dose determination study.
Intervention Type
Drug
Intervention Name(s)
GSK3326595
Intervention Description
GSK3326595 will be administered with and without food, in tablet and capsule formulation.
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Intervention Description
Pembrolizumab will be administered.
Primary Outcome Measure Information:
Title
Parts 1 and 3: Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions
Description
All AEs, SAEs and dose modifications will be collected.
Time Frame
Up to approximately 2 years
Title
Part 1: Number of participants with dose limiting toxicities (DLTs)
Description
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.
Time Frame
Up to 21 days
Title
Parts 1 and 3: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters.
Description
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.
Time Frame
Up to approximately 2 years
Title
Part 2: Participants with solid tumors (non-GBM): Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1
Description
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Time Frame
Up to approximately 2 years
Title
Part 2: Participants with NHL: ORR based on Lugano criteria
Description
ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.
Time Frame
Up to approximately 2 years
Title
Part 2: GBM cohort: Six-month progression free survival (PFS) rate
Description
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.
Time Frame
Up to 6 months
Secondary Outcome Measure Information:
Title
Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595
Description
Blood samples will be collected at given time points to determine the Cmax of GSK3326595.
Time Frame
Baseline and up to approximately 2 years
Title
Parts 1 and 3: Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of GSK3326595
Description
Blood samples will be collected at given time points to determine the AUC (0-inf) of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3326595
Description
Blood samples will be collected at given time points to determine the AUC (0-t) of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: AUC over the dosing interval tau (AUC[0-tau]) of GSK3326595
Description
Blood samples will be collected at given time points to determine the AUC (0-tau) of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: Terminal phase half-life (t1/2) of GSK3326595
Description
Blood samples will be collected at given time points to determine the half-life of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: Oral clearance (CL/F) of GSK3326595
Description
Blood samples will be collected at given time points to determine the CL/F of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: Accumulation ratio (AR) of GSK3326595
Description
Blood samples will be collected at given time points to determine the AR of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Parts 1 and 3: Time invariance (TI) of GSK3326595
Description
Blood samples will be collected at given time points to determine the TI of GSK3326595.
Time Frame
Up to approximately 2 years
Title
Part 1: Participants with solid tumors: Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1
Description
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RECIST 1.1 criteria.
Time Frame
Up to approximately 2 years
Title
Part 3: ORR based on immune-based RECIST (iRECIST) criteria
Description
ORR is defined as the percentage of participants achieving confirmed CR or confirmed PR based on immune-based RECIST (iRECIST) criteria.
Time Frame
Up to approximately 2 years
Title
Part 2: PFS
Description
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.
Time Frame
Up to approximately 2 years
Title
Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria
Description
ORR is defined as the percentage of participants achieving a confirmed complete response (CR) or partial response (PR) based on RANO working group criteria.
Time Frame
Up to approximately 2 years
Title
Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR)
Description
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.
Time Frame
Up to approximately 2 years
Title
Part 2: (Participants in ACC tablet cohort): Overall survival (OS)
Description
OS is defined as the time from first dose until death from any cause.
Time Frame
Up to approximately 2 years
Title
Part 2: Number of participants with any AEs, SAEs, withdrawal due to AEs, dose reductions or delays
Description
All AEs, SAEs and dose modifications will be collected.
Time Frame
Up to approximately 2 years
Title
Part 2: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters
Description
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.
Time Frame
Up to approximately 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
GSK Investigational Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
GSK Investigational Site
City
Middletown
State/Province
New Jersey
ZIP/Postal Code
07748
Country
United States
Facility Name
GSK Investigational Site
City
Harrison
State/Province
New York
ZIP/Postal Code
10604
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
Facility Name
GSK Investigational Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
GSK Investigational Site
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
GSK Investigational Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 1Z5
Country
Canada
Facility Name
GSK Investigational Site
City
Bordeaux Cedex
ZIP/Postal Code
33076
Country
France
Facility Name
GSK Investigational Site
City
Lyon Cedex 08
ZIP/Postal Code
69373
Country
France
Facility Name
GSK Investigational Site
City
Villejuif cedex
ZIP/Postal Code
94805
Country
France
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1066 CX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands
Facility Name
GSK Investigational Site
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD for this study will be made available via the Clinical Study Data Request site.
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
http://clinicalstudydatarequest.com
Learn more about this trial
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
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