Pharmacokinetics of Osimertinib in Chinese Patients With Advanced NSCLC: A Phase 1 Study

Abstract Osimertinib is an oral, irreversible, central nervous system active epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI) selective for both EGFR‐TKI sensitizing and T790M resistance mutations. The study's (NCT02529995) primary objective was to characterize the pharmacokinetics (PK) of osimertinib and its metabolites in Chinese patients enrolled in China. PK was assessed following single and multiple doses of 40 or 80 mg osimertinib once daily. Patients were aged ≥ 18 years with locally advanced or metastatic EGFR‐TKI‐sensitizing (EGFRm) non–small cell lung cancer and World Health Organization performance status of 0/1, who had progressed following prior EGFR‐TKI. Thirty‐one patients were assigned to treatment (40 mg, n = 15; 80 mg, n = 16), and 25 were included in the PK analyses set (40 mg, n = 12; 80 mg, n = 13). Six were excluded from analyses because of prior treatment with an osimertinib‐like substance. At steady state a flat PK profile with a low maximum–minimum plasma concentration ratio was observed. Investigator‐assessed objective response rate was 47% (7 of 15; 95%CI, 21.3–73.4) in the 40‐mg cohort and 75% (12 of 16; 95%CI, 47.6–92.7) in the 80‐mg cohort. Adverse events (AEs) leading to dose modification and treatment discontinuation were reported in 2 patients (6%) and 3 patients (10%), respectively. Serious AEs were reported in 8 patients (26%) and AEs leading to death in 1 patient (3%). Interstitial lung disease/pneumonitis‐like event was reported in 1 patient (3%). Osimertinib PK in a Chinese patient population is well characterized and consistent with the global population, supporting the use of a once‐daily 80‐mg dose.