Effect of Food Intake on Pharmacokinetics of Oral Almonertinib: A Randomized Crossover Trial in Healthy Chinese Participants

Abstract The third‐generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) almonertinib (HS‐10296) targets both EGFR‐sensitizing and T790M resistance mutations. This randomized, open‐label, two‐period crossover trial investigated the effect of food intake on the single‐dose pharmacokinetic properties of almonertinib and its metabolite HAS‐719. Twenty healthy adults received a single dose of almonertinib tablets (110 mg) on days 1 and 22 under overnight fasting or fed conditions, respectively. Plasma samples were collected 216 hours post‐dosing and almonertinib and HAS‐719 concentrations were determined using liquid chromatography‐tandem mass spectrometry. For almonertinib, the geometric mean ratio (GMR, fed/fasting) and 90% confidence interval (CI) for the area under the curve (AUC) from time 0 to 216 hours and apparent oral clearance (CL z /F) were 119.9 (110.0–130.7) and 83.5 (76.6–90.9), respectively. Fasting and fed groups showed significant differences in these parameters, but not for maximum concentration (C max ) and time to C max (T max ). The C max GMR of HAS‐719 was 81.7 (75.8–88.0), which decreased significantly in the fed group. The drug‐related adverse reaction (AR) incidence was similar in the two groups, 50% in the fasting group and 52.6% in the fed group. ARs were mainly gastrointestinal diseases and abnormal laboratory test results, and all participants fully recovered. In conclusion, a high‐fat diet slightly affected the pharmacokinetic profile of almonertinib in healthy participants, but not the safety tolerance. Therefore, almonertinib is suitable for administration under fasting or fed conditions.