Director, Clinical Pharmacology EQRx International, Inc. Napa, California, United States
Background: Aumolertinib is a novel, third generation EGFR tyrosine kinase inhibitor that selectively inhibits both EGFR sensitizing and T790M mutations and is in clinical development for the treatment of non-small cell lung cancer. This Phase 1 study compared the pharmacokinetics (PK) of aumolertinib in non-Chinese vs Chinese healthy subjects to assess the effect of ethnic sensitivity of aumolertinib PK. Methods: This was an open-label, non-randomized study. Healthy subjects received a single oral dose of 110 mg aumolertinib. Serial PK samples were collected and safety was assessed throughout the study. An analysis of variance using a mixed-effects model was applied to the natural logarithmic transformation of primary PK parameters (AUCinf and Cmax) for aumolertinib and its major metabolite (MET). Geometric mean ratios (GMR) and 90% confidence intervals (CI) were estimated for all subjects. Results: Fifteen Chinese and thirty non-Chinese subjects (15 Caucasian, 7 Black/African American, 8 Hispanic/Latino) were enrolled. All subjects completed study treatment. The mean (range) age was 35 (18-61) years, and 49% were male. Aumolertinib and major MET exposures were comparable between Chinese and non-Chinese healthy subjects. The GMR (90% CI) for AUCinf and Cmax of aumolertinib were 1.2 (0.93, 1.6) and 1.2 (0.94, 1.4), respectively, and for MET were 1.1 (0.91, 1.3) and 0.94 (0.80, 1.1), respectively, indicating no clinically relevant difference in exposures between Chinese and non-Chinese healthy subjects. The incidence of treatment-related AEs was low ( < 24%) and the safety profiles were similar between the different ethnicities evaluated in this study. Conclusion: Results of this study indicate that aumolertinib PK is not sensitive to differences in ethnicity. No dose adjustment for aumolertinib is warranted based on ethnicity.
