PURPOSE: Osimertinib (AZD9291) 80 mg once daily is approved by the US FDA for 
the treatment of patients with metastatic EGFR T790M-positive NSCLC whose 
disease has previously progressed on EGFR-TKI therapy. Osimertinib PK was 
evaluated to define the dose and dosing interval, whether a fixed-dosing 
approach can be used globally, and the impact of formulation and food on 
exposure.
METHODS: AURA (NCT01802632): single- and multiple-dose PK of osimertinib 
(20-240 mg daily) was determined in patients with advanced NSCLC. 
Bioavailability study (NCT01951599): single-dose PK of osimertinib (20 mg) was 
determined in healthy volunteers with administration of capsule, solution, or 
tablet formulations fasted, and as a tablet in the fed and fasted state.
RESULTS: Osimertinib was slowly absorbed and displayed dose-proportional 
increases in exposure from 20 to 240 mg. Distribution was extensive and 
clearance low to moderate, resulting in a mean half-life of 48.3 h. Steady state 
was achieved by 15 days of dosing, consistent with single-dose PK, with a 
peak-to-trough ratio of 1.6. Two active metabolites circulated at ~10 % of 
osimertinib exposure. Ethnicity did not appear to affect exposure. Osimertinib 
PK profiles in healthy volunteers were similar to those in patients and were 
unaffected by formulation. Food caused a clinically insignificant increase in 
exposure.
CONCLUSIONS: Osimertinib PK supports once-daily dosing; the same dose for Asian 
and non-Asian populations; a fixed-dosing approach; a minimal effect of food on 
exposure; and a switch to tablet formulation without alteration to dose or 
schedule. Osimertinib plasma concentrations are sustained throughout the dosing 
period, which is considered optimal for efficacy.