Meteor 1: 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
Study Details
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).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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.
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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.
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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.
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Outcome Measures
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 [Up to approximately 2 years]
All AEs, SAEs and dose modifications will be collected.
- Part 1: Number of participants with dose limiting toxicities (DLTs) [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.
- Parts 1 and 3: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters. [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.
- Part 2: Participants with solid tumors (non-GBM): Overall response rate (ORR) based on Evaluation Criteria In Solid Tumors (RECIST) 1.1 [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.
- Part 2: Participants with NHL: ORR based on Lugano criteria [Up to approximately 2 years]
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 [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
- Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595 [Baseline and up to approximately 2 years]
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 [Up to approximately 2 years]
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 [Up to approximately 2 years]
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 [Up to approximately 2 years]
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 [Up to approximately 2 years]
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 [Up to approximately 2 years]
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 [Up to approximately 2 years]
Blood samples will be collected at given time points to determine the AR of GSK3326595.
- Parts 1 and 3: Time invariance (TI) of GSK3326595 [Up to approximately 2 years]
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 [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.
- Part 3: ORR based on immune-based RECIST (iRECIST) criteria [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.
- Part 2: PFS [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.
- Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria [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.
- Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR) [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 Investigator Assessment.
- Part 2: (Participants in ACC tablet cohort): Overall survival (OS) [Up to approximately 2 years]
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 [Up to approximately 2 years]
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 [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.
Eligibility Criteria
Criteria
Inclusion criteria:
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Males and females greater than or equal to (>=)18 years of age (at the time consent is obtained)
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Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 or 2
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Diagnosis of non-resectable or metastatic solid malignancy (as defined in the protocol) or NHL
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Presence of evaluable disease
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Adequate organ function (as defined in the protocol)
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Reproductive criteria (as defined in the protocol).
Exclusion Criteria:
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Malignancy attributed to prior solid organ transplant
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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)
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History of a second malignancy, excluding non-melanoma skin cell cancer within the last three years
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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
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Any clinically significant gastrointestinal (GI) abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach and/or bowels.
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Select cardiac abnormalities (as defined in the protocol)
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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.
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History of optic nerve neuropathy or neuritis.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | GSK Investigational Site | Denver | Colorado | United States | 80218 |
2 | GSK Investigational Site | Miami | Florida | United States | 33136 |
3 | GSK Investigational Site | Middletown | New Jersey | United States | 07748 |
4 | GSK Investigational Site | Harrison | New York | United States | 10604 |
5 | GSK Investigational Site | New York | New York | United States | 10065 |
6 | GSK Investigational Site | Nashville | Tennessee | United States | 37203 |
7 | GSK Investigational Site | Dallas | Texas | United States | 75230 |
8 | GSK Investigational Site | San Antonio | Texas | United States | 78229 |
9 | GSK Investigational Site | Edmonton | Alberta | Canada | T6G 1Z2 |
10 | GSK Investigational Site | Ottawa | Ontario | Canada | K1H 8L6 |
11 | GSK Investigational Site | Toronto | Ontario | Canada | M5G 1Z5 |
12 | GSK Investigational Site | Bordeaux Cedex | France | 33076 | |
13 | GSK Investigational Site | Lyon Cedex 08 | France | 69373 | |
14 | GSK Investigational Site | Villejuif cedex | France | 94805 | |
15 | GSK Investigational Site | Amsterdam | Netherlands | 1066 CX | |
16 | GSK Investigational Site | Leiden | Netherlands | 2333 ZA | |
17 | GSK Investigational Site | Rotterdam | Netherlands | 3015 GD |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 204653
- 2016-000278-39