E13065 Background: Crizotinib is a selective, ATP-competitive, small molecule inhibitor of the ALK and MET/HGF receptor tyrosine kinases. Crizotinib is currently being developed as an orally administered agent in treatment of advanced ALK-positive NSCLC. The recommended clinical dose is 250 mg BID. Methods: Plasma crizotinib concentration data were collected in an ongoing, open-label, multi-center phase I study (J Clin Oncol 28:15s, 2010). A total of 167 patients receiving crizotinib at a dose of 250 mg BID who had at least 1 measurable plasma concentration of crizotinib were included in this PK analysis. Of these, 118 patients were ALK-positive NSCLC patients; and 42 were Asian and 125 were non‐Asian (including White, Black, and Other). The mean age was 51.0 years, and the mean weight was 70.7 kg. Results: After a single crizotinib dose of 250 mg, crizotinib Cmax was achieved at a median Tmax of 4.0 hours and the mean apparent terminal half life was 42 hours. Neither age, gender, race or body weight appeared to have overt effects on the single-dose crizotinib PK. After repeated dosing at 250 mg BID, crizotinib plasma concentrations appeared to reach steady state within 15 days. Crizotinib appeared to exhibit non-linear PK as reflected by decreases in CL/F observed with multiple dosing. The geometric mean values for CL/F following 15 and 28 Days of dosing of 64.5 L/hr and 60.1 L/hr, respectively, were lower than that seen after a single dose (100 L/hr). Crizotinib PK in the ALK-positive NSCLC patients was similar to that seen for patients with other tumor types. Mean values for crizotinib Cmax and AUC in Asian patients were 1.57- (90% CI: 1.16-2.13) and 1.50- (90% CI: 1.10 2.04) fold those seen in non-Asian patients, respectively. Comparison of BW-adjusted crizotinib PK parameters suggests that body size may be a factor that influences the observed PK difference. Conclusions: The observed change in CL/F prior to and after achievement of steady-state was likely due to autoinhibition of CYP3A. Increased systemic exposure to crizotinib was seen in Asian patients, however, based on the safety and efficacy profile, no dose adjustment is warranted seen in this population.