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GSK2256098

Phase 1

Cancer | Small molecule | Oncology |GSK plc|Last Updated: Jul 12, 2019

Success Probability

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Trial Design

RandomizedCONTROLLED
Total Trials3
Total Enrollment146

FDA Designations

No designations recorded

Clinical trial landscape

GSK2256098 · 3 trials · 2 indications

Phase 1 3
NCT01938443A Dose Escalation Study to Assess Safety of GSK2256098 (FAK Inhibitor) in Combination With Trametinib (MEK Inhibitor) in Subjects With Advanced Solid TumorsCancer
COMPLETED34 Analytics
NCT01138033Study of a Focal Adhesion Kinase Inhibitor in Subjects With Solid TumorsCancer
COMPLETED74 Analytics
NCT00996671Phase I Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2256098 in Healthy VolunteersCancer
COMPLETED38 Analytics
PHASE1COMPLETED
A Dose Escalation Study to Assess Safety of GSK2256098 (FAK Inhibitor) in Combination With Trametinib (MEK Inhibitor) in Subjects With Advanced Solid Tumors
CancerUnlock trial analytics
PHASE1COMPLETED
Study of a Focal Adhesion Kinase Inhibitor in Subjects With Solid Tumors
CancerUnlock trial analytics
PHASE1COMPLETED
Phase I Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2256098 in Healthy Volunteers
CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Part 1: Safety assessment as assessed by adverse events (AEs) and serious adverse events (SAEs)
From Day 1 till post study visit (approximately 21 days from last dose)

AEs and SAEs will be assessed to determine the MTD and RP2D combination of GSK2256098 and trametinib.

Part 1: Safety assessment as assessed by 12-lead electrocardiogram (ECG)
Screening, Day 1, Day 15, Day 22, and every 8 weeks from first dose till post study visit (approximately 21 days from last dose)

Twelve lead ECGs will be obtained to determine the MTD and RP2D combination of GSK2256098 and trametinib.

Part 1: Safety assessment as assessed by vital signs
From Day 1 till post study visit (approximately 21 days from last dose)

Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and temperature

Part 1: Safety assessment as assessed by change from baseline in laboratory values
From Day 1 till post study visit (approximately 21 days from last dose)

Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters

Part 1: Safety assessment as assessed by echocardiogram
Screening, Day 28 and Day 1 of Weeks 13, 21, 33, then every 12 weeks.

Echocardiograms will be performed to assess cardiac ejection fraction.

Part 1: Safety assessment as assessed by eye examination
Screening and as clinically warranted

A standard ophthalmic exam will be performed by an ophthalmologist.

Part 1: Safety assessment as assessed by urine protein to creatinine (UPC) ratio
From Day 1 till post study visit (approximately 21 days from last dose)

Urine samples will be collected for the analyses of UPC ratio.

Part 2: Long term safety assessment as assessed by AEs and SAEs
From Day 1 till post study visit (approximately 21 days from last dose)

AEs and SAEs will be recorded to assess longer term safety of the GSK2256098/trametinib combination at the RP2D in a larger cohort of subjects with MPM.

Part 2: Long term safety assessment as assessed by 12-lead ECG
Screening, Day 1, Day 15, Day 22, and every 8 weeks from first dose till post study visit (approximately 21 days from last dose)

Twelve lead ECGs will be obtained to assess longer term safety of the GSK2256098/trametinib combination at the RP2D in a larger cohort of subjects with MPM

Part 2: Long term safety assessment as assessed by vital signs
From Day 1 till post study visit (approximately 21 days from last dose)

Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and temperature

Part 2: Long term safety assessed as change from baseline in laboratory values
From Day 1 till post study visit (approximately 21 days from last dose)

Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters

Part 2: Long term safety assessment as assessed by echocardiogram
Screening, Day 28 and Day 1 of Weeks 13, 21, 33, then every 12 weeks.

Echocardiograms will be performed to assess cardiac ejection fraction.

Part 2: Long term safety assessment as assessed by eye examination
Screening and as clinically warranted

A standard ophthalmic exam will be performed by an ophthalmologist.

Part 2: Long term safety assessment as assessed by UPC ratio
From Day 1 till post study visit (approximately 21 days from last dose)

Urine samples will be collected for the analyses of UPC ratio.

To evaluate the Maximum tolerated dose, identify the recommended Phase 2 dose(s), dose limiting toxicities, safety and tolerability of GSK2256098 given orally on consecutive days.
Until disease progression
To characterize the safety of single doses of GSK2256098 in adult healthy subjects
within 10-14 days following administration of study drug
To characterize the single dose pharmacokinetics of GSK2256098 in blood and urine in adult healthy subjects
14 days after administration of study drug

Secondary Endpoints

Part 1: GSK2256098 and trametinib PK assessment following repeat-dose (Day 15) administration of GSK2256098 and trametinib
Day 15 (pre-dose, 1, 1.5, 2, 4, 6, 8 hours)
Part 1: Tumor response and analysis of change from baseline levels of PD markers including pFAK/FAK, and pERK/ERK measured in tumor biopsies
Screening (before the first dose on Day 1), Day 15 and 22
Part 2: Tumor response as measured by modified Response Evaluation Criteria In Solid Tumors (RECIST) for mesothelioma
Screening, Every 8 weeks from first dose and at progression and post study (approximately 21 days from last dose)
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Study Design & Arms

AllocationRANDOMIZED
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Part 1EXPERIMENTALPart 1 will determine the MTD and RP2D based on the safety and tolerability of GSK2256098 administered with trametinib. Subject will be administered starting dose of 1.0 mg OD trametinib combined with 500 mg BID GSK2256098. Dose escalation will continue until the MTD is established.
Part 2EXPERIMENTALBased on determination of combination dose regimen in Part 1, dose expansion cohorts for Part 2 will be opened.
Part 3EXPERIMENTALPart 3 - Characterize the biologically active dose range by analysis of PD markers in skin, hair and in tumor tissue in subjects with solid tumors amendable to biopsy and know to over express FAK
Part 4EXPERIMENTALPart 4 - Explore further the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM).
Part 5EXPERIMENTALPart 5 will investigate the time course, the extent of an apparent change in the PK of GSK2256098 following repeated dosing, and screen for potential CYP3A induction as a possible mechanism of reduced systemic exposure of GSK2256098 at Day 15 and later time points.
Dose Escalation CohortsEXPERIMENTALsingle dose administration escalating doses starting at 20 mg and continue escalation; the highest dose in this study will not exceed the mean Day 1 exposure in male dogs at the NOAEL dose (6 mg/kg/day).
Food effect CohortEXPERIMENTALDose to be selected based on emerging safety and PK data; subjects will be given FDA standard high fat meal followed by single dose of study drug.

Interventions

NameTypeDescription
GSK2256098DRUGGSK2256098 250 mg will be supplied as white to off-white, round, biconvex tablets with no markings. GSK2256098 will be administered 30 minutes after a light meal with approximately 240 milliliter of water.
TrametinibDRUGTrametinib 0.5 mg will be supplied as capsules with no identifying markings. Trametinib will be administered orally under fasting conditions two hours after a meal.
PlaceboDRUGPlacebo to be used as comparator for GSK2256098
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites4

Inclusion Criteria Part 1 Subject Inclusion Criteria: * Subjects with measurable tumors that may benefit from treatment with GSK2256098 and trametinib. This includes mesothelioma along with tumors with a high likelihood of MAPK pathway activation as reported in the medical literature. Part 2 Subj...

Countries:FranceUnited KingdomAustralia
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Frequently asked questions about GSK2256098

What is GSK2256098 used for?

GSK2256098 is an investigational small molecule being developed for the treatment of cancer. It has been studied in Phase 1 clinical trials in patients with solid tumors and advanced cancers, as well as in healthy volunteers. The drug is not approved and remains in clinical development.

What does GSK2256098 target?

GSK2256098 is a focal adhesion kinase (FAK) inhibitor. It works by inhibiting FAK, an enzyme involved in tumor growth and metastasis. The drug has been studied as a monotherapy and in combination with the MEK inhibitor trametinib in patients with advanced solid tumors.

Who makes GSK2256098?

GSK2256098 is being developed by GSK plc, a global biopharmaceutical company listed on the London Stock Exchange under the ticker GSK. The company has sponsored multiple Phase 1 clinical trials evaluating the drug in oncology indications.

What phase is GSK2256098 in?

GSK2256098 is in Phase 1 clinical development. All three completed trials were Phase 1 studies, including a healthy volunteer study and two trials in patients with solid tumors. The drug is investigational and has not received regulatory approval.

What clinical trials is GSK2256098 in?

GSK2256098 has been studied in three completed Phase 1 trials: NCT00996671 in healthy volunteers, NCT01138033 in subjects with solid tumors, and NCT01938443 in combination with trametinib in advanced solid tumors. Total enrollment across these trials was 146 participants.

Is GSK2256098 the same as a FAK inhibitor?

Yes, GSK2256098 is a focal adhesion kinase (FAK) inhibitor. It has been evaluated as a single agent and in combination with the MEK inhibitor trametinib. The drug is being studied for its potential role in treating various types of cancer.