Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01938443 | A Dose Escalation Study to Assess Safety of GSK2256098 (FAK Inhibitor) in Combination With Trametinib (MEK Inhibitor) in Subjects With Advanced Solid Tumors | PHASE1 | COMPLETED | 34 | — | — | Nov 18, 2013 | Jun 23, 2016 | Jul 12, 2019 | 4 | France, United Kingdom |
| NCT01138033 | Study of a Focal Adhesion Kinase Inhibitor in Subjects With Solid Tumors | PHASE1 | COMPLETED | 74 | — | — | Jul 27, 2010 | Dec 21, 2015 | May 11, 2017 | 10 | Australia, France +1 |
| NCT00996671 | Phase I Study to Evaluate Safety, Pharmacokinetics and Pharmacodynamics of GSK2256098 in Healthy Volunteers | PHASE1 | COMPLETED | 38 | — | — | Nov 6, 2009 | Mar 17, 2010 | Jun 14, 2017 | 1 | Australia |
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 |
|---|---|---|
| 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 |
|---|---|---|
| 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 |
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...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| GE Healthcare Technologies Inc. | GEHC | 1 | PHASE1 | GEH200520 / GEH200521 - Part A |
| Zimmer Biomet Holdings, Inc. | ZBH | 1 | — | Undisclosed |
| Ascentage Pharma Group International Unsponsored ADR | AAPG | 1 | PHASE1 | Olverembatinib |