This is a Phase I, open-label, 2-part study in patients with a confirmed diagnosis of epidermal growth factor receptor (EGFR) mutation positive (EGFRm+) non-small cell lung cancer (NSCLC), who have progressed following prior therapy with an approved EGFR tyrosine kinase inhibitor (TKI) agent. Part A will assess the effect of AZD9291 on the pharmacokinetic (PK) parameters of simvastatin and simvastatin acid, following multiple oral dosing of AZD9291 in a fasted state. Part B will allow patients further access to AZD9291 after the PK phase (Part A) and will provide for additional safety data collection. All patients from Part A who completed treatment may continue to receive AZD9291 80 mg once daily until: disease progression; they are no longer deriving clinical benefit; or any other reason.
Name: Pharmacokinetic sampling - AZD9291
Name: Simvastatin
Name: AZD9291 tablet dosing
Name: Pharmacokinetic sampling - simvastatin
Name: Pharmacokinetic sampling - AZ5140 and AZ7550
Description: Pharmacokinetics of simvastatin by assessment of maximum plasma simvastatin concentration
Measure: Cmax of Simvastatin Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Pharmacokinetics of simvastatin by assessment of area under the plasma concentration time curve from zero to infinity
Measure: AUC of Simvastatin Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Pharmacokinetics of simvastatin and simvastatin acid by time to Cmax
Measure: Tmax of Simvastatin and Simvastatin Acid Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Rate and extent of absorption of simvastatin by assessment of apparent clearance following oral administration
Measure: CL/F of Simvastatin Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Pharmacokinetics of simvastatin acid by assessment of maximum plasma simvastatin acid concentration
Measure: Cmax of Simvastatin Acid Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Pharmacokinetics of simvastatin acid by assessment of area under the plasma concentration time curve from zero to infinity
Measure: AUC of Simvastatin Acid Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part ADescription: Pharmacokinetics of simvastatin and simvastatin acid by assessment of area under the plasma concentration time curve from time zero to last quantifiable dose
Measure: AUC(0-t) of Simvastatin and Simvastatin Acid Time: Blood samples collected on Days 1 and 31 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 28, and 32 hours post simvastatin dose in Part AAllocation: N/A
Single Group Assignment
There are 2 SNPs
4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G). 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. --- L858R ---
4. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including G719X, exon 19 deletion, L858R, L861Q). 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 with no deterioration over the previous 2 weeks (Appendix G). 6. Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening. --- L858R --- --- L861Q ---