Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as FAK Inhibitor GSK2256098
GSK2256098 · 4 trials · 5 indications
Point estimates and 95% binomial confidence intervals will be generated for the six month PFS rate within each cohort of each treatment arm. Kaplan-Meier curves will be generated for PFS for each cohort within each treatment arm.
Point estimates will be generated for response rates within each treatment arm with corresponding 95% binomial confidence intervals.
AEs and SAEs will be assessed to determine the MTD and RP2D combination of GSK2256098 and trametinib.
Twelve lead ECGs will be obtained to determine the MTD and RP2D combination of GSK2256098 and trametinib.
Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and temperature
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
Echocardiograms will be performed to assess cardiac ejection fraction.
A standard ophthalmic exam will be performed by an ophthalmologist.
Urine samples will be collected for the analyses of UPC ratio.
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.
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
Vital sign measurements will include systolic and diastolic blood pressure, pulse rate, and temperature
Clinical laboratory assessments will include hematology, clinical chemistry, routine urinalysis and additional parameters
Echocardiograms will be performed to assess cardiac ejection fraction.
A standard ophthalmic exam will be performed by an ophthalmologist.
Urine samples will be collected for the analyses of UPC ratio.
| Arm | Type | Description |
|---|---|---|
| Arm A (vismodegib) | EXPERIMENTAL | Patients receive vismodegib PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL FEBRUARY 2018) |
| Arm B (FAK inhibitor GSK2256098) | EXPERIMENTAL | Patients receive FAK inhibitor GSK2256098 PO BID. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED TO ACCRUAL JULY 2017) |
| Arm C (capivasertib) | EXPERIMENTAL | Patients receive capivasertib PO BID on days 1-4. Treatment repeats every 7 days for up to 1 cycle (28 days) in the absence of disease progression or unacceptable toxicity. |
| Arm D (abemaciclib) | EXPERIMENTAL | Patients receive abemaciclib PO Q12H. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
| Part 1 | EXPERIMENTAL | Part 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 2 | EXPERIMENTAL | Based on determination of combination dose regimen in Part 1, dose expansion cohorts for Part 2 will be opened. |
| Part 3 | EXPERIMENTAL | Part 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 4 | EXPERIMENTAL | Part 4 - Explore further the safety, PK, tolerability and anti-tumor activity of GSK2256098 in subjects with relapsed glioblastoma multiforme (GBM). |
| Part 5 | EXPERIMENTAL | Part 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 Cohorts | EXPERIMENTAL | single 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 Cohort | EXPERIMENTAL | Dose 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. |
| Name | Type | Description |
|---|---|---|
| Vismodegib | DRUG | Given PO |
| FAK Inhibitor GSK2256098 | DRUG | Given PO |
| Capivasertib | DRUG | Given PO |
| Abemaciclib | DRUG | Given PO |
| GSK2256098 | DRUG | GSK2256098 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. |
| Trametinib | DRUG | Trametinib 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. |
| Placebo | DRUG | Placebo to be used as comparator for GSK2256098 |
* Documentation of disease: * Histologic documentation: histologically proven intracranial meningioma as documented by central pathology review * Molecular documentation: Presence of SMO, PTCH1, NF2, CDKN2A, AKT1, PIK3CA, PTEN mutations, CDKN2A copy number loss, CDK4, CDK6, CCND1, CCND2, CCND3,...
GSK2256098 is an investigational small molecule drug being developed by GSK plc for the treatment of cancer. It is being studied in solid tumors and intracranial meningioma, including recurrent meningioma and tumors associated with NF2 gene mutation. It is not yet approved and remains in clinical development.
GSK2256098 targets PTK2, also known as focal adhesion kinase (FAK). It acts as an inhibitor of this target. PTK2 is a protein tyrosine kinase involved in cellular signaling, and inhibiting it is the intended mechanism of action for this small molecule in oncology research.
GSK2256098 is developed by GSK plc, which trades under the ticker GSK. The company sponsors the clinical trials evaluating the drug in cancer and intracranial meningioma. It is also referred to as FAK Inhibitor GSK2256098, a name that reflects its molecular target.
GSK2256098 is in Phase 1 development overall, with three completed Phase 1 trials. One Phase 2 trial, NCT02523014, is currently recruiting and is testing GSK2256098 in combination with other agents in patients with progressive meningiomas. The drug is investigational and has not been approved.
GSK2256098 has been studied in several trials. NCT02523014 is a recruiting Phase 2 study in progressive meningiomas. NCT01938443 was a completed Phase 1 study combining GSK2256098 with trametinib in advanced solid tumors, and NCT01138033 was a completed Phase 1 study in solid tumors. NCT00996671 evaluated the drug in healthy volunteers.
Yes. FAK Inhibitor GSK2256098 is another name for GSK2256098. The alternative name describes the drug's mechanism, since GSK2256098 inhibits focal adhesion kinase, also known as PTK2. Both names refer to the same investigational small molecule developed by GSK plc.