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).
Title
- 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
- 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 IDs
- ORG STUDY ID:
204653
- SECONDARY ID:
2016-000278-39
- NCT ID:
NCT02783300
Conditions
Interventions
Drug | Synonyms | Arms |
---|
GSK3326595 | | Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet |
Pembrolizumab | | Part 3: GSK3326595 in combination with pembrolizumab |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Part 1: Dose Escalation, Food effect and Relative Bioavailability of Capsule formulation to Tablet | Experimental | 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). | |
Part 2: Disease-Specific Expansion cohort | Experimental | 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. | |
Part 3: GSK3326595 in combination with pembrolizumab | Experimental | Participants with selected solid tumors will be administered GSK3326595 in combination with pembrolizumab as part of this dose determination study. | |
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Parts 1 and 3: Number of participants with any adverse events (AEs), serious adverse events (SAEs), withdrawal due to AEs, dose interruptions and reductions |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | All AEs, SAEs and dose modifications will be collected. |
Secondary Outcome Measures
Measure: | Parts 1, 2 and 3: Change from Baseline in symmetrical arginine dimethylation (SDMA) as a PD measure |
Time Frame: | Baseline and up to approximately 2 years |
Safety Issue: | |
Description: | Evaluation of change from baseline in SDMA, a PD biomarker of PRMT5 inhibition. |
Measure: | Parts 1 and 3: Maximum observed plasma concentration (Cmax) of GSK3326595 |
Time Frame: | Baseline and up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the Cmax of GSK3326595. |
Measure: | Parts 1 and 3: Area under the plasma concentration-time curve (AUC) extrapolated from time zero to infinity (AUC[0-inf]) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the AUC (0-inf) of GSK3326595. |
Measure: | Parts 1 and 3: AUC from time zero to the last quantifiable concentration after dosing (AUC[0-t]) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the AUC (0-t) of GSK3326595. |
Measure: | Parts 1 and 3: AUC over the dosing interval tau (AUC[0-tau]) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the AUC (0-tau) of GSK3326595. |
Measure: | Parts 1 and 3: Terminal phase half-life (t1/2) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the half-life of GSK3326595. |
Measure: | Parts 1 and 3: Oral clearance (CL/F) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the CL/F of GSK3326595. |
Measure: | Parts 1 and 3: Accumulation ratio (AR) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the AR of GSK3326595. |
Measure: | Parts 1 and 3: Time invariance (TI) of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected at given time points to determine the TI of GSK3326595. |
Measure: | Parts 1 and 2 (Participants with ACC only) ORR based on RECIST 1.1 criteria |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
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. |
Measure: | Part 3: ORR based on immune-based RECIST (iRECIST) criteria |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | ORR is defined as the percentage of participants achieving confirmed CR or confirmed PR based on immune-based RECIST (iRECIST) criteria. |
Measure: | Part 2: PFS |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
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. |
Measure: | Part 2: ORR in participants with GBM based on Response Assessment Neuro-Oncology (RANO) Working group criteria |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
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. |
Measure: | Part 2: (Participants in ACC tablet cohort): Duration of Response (DOR) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
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 ICR. |
Measure: | Part 2: (Participants in ACC tablet cohort): Overall survival (OS) |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | OS is defined as the time from first dose until death from any cause. |
Measure: | Part 2: Number of participants with any AEs, SAEs, withdrawal due to AEs, dose reductions or delays |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | All AEs, SAEs and dose modifications will be collected. |
Measure: | Part 2: Number of participants with clinically significant changes in laboratory parameters, vital signs, physical examination and organ-specific parameters |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
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. |
Measure: | Part 2: ORR relative to p53 mutational status in participants with NHL |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | P53 mutational status is collected for participants with NHL to determine the relationship between p53 status and ORR. |
Measure: | Part 2: AUC of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected to determine AUC of GSK3326595. |
Measure: | Part 2: Cmax of GSK3326595 |
Time Frame: | Up to approximately 2 years |
Safety Issue: | |
Description: | Blood samples will be collected to determine Cmax of GSK3326595. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | GlaxoSmithKline |
Trial 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
Last Updated
May 17, 2021