Effects of food and race on the pharmacokinetics of lazertinib in healthy subjects and patients with EGFR mutation-positive advanced non-small cell lung cancer. (January 2023)

• Record Type: Journal Article
• Authors: Huh, Ki Young; Lim, Yeji; Yoon, Deok Yong; Hwang, Jun Gi; Sim, Sujin; Kang, Jiah; Wang, Jangyoung; Kim, Mikyung; Jang, Seong Bok; Shreeve, S. Martin; Mehta, Jaydeep; Haddish-Berhane, Nahor; Oh, Jaeseong; Lee, SeungHwan; Yu, Kyung-Sang
• Is Part Of: Lung cancer. Volume 175(2023)
• Page Start: 112
• Page End: 120
• Publication Date: 2023-01
• Subjects: ADR adverse drug reactions -- AE adverse event -- ANOVA analysis of variance -- AUC area under the time-concentration curve -- AUCinf area under the time-concentration curve extrapolated to infinity -- AUCss area under the time-concentration curve during the dosing interval at steady state -- AUCt area under the time-concentration curve to the last quantitative concentration after a single dose -- BCRP (breast cancer resistance protein -- CI confidence interval -- CL/F apparent clearance -- Clast last measurable concentration -- Cmax maximum plasma concentration after a single dose -- Cmax ss, maximum plasma concentration after a single dose at steady state -- CNS central nervous system -- CYP cytochrome P450 -- DN dose-normalized -- ECG electrocardiograms -- ECOG PS European Cooperative Oncology Group performance status -- EDTA ethylene-diamine-tetraacetic acid -- EGFR epidermal growth factor receptor -- NSCLC non-small cell lung cancer -- PK pharmacokinetics -- QD once daily -- t1/2 terminal half-life -- T790M threonine to methionine substitution at amino acid position 790 -- TKI tyrosine kinase inhibitor -- Tmax time to reach the maximum plasma concentration -- Vd/F apparent volume of distribution -- λz terminal elimination rate constant; Genes -- erbB-1 -- Pharmacokinetics -- Adenocarcinoma of lung -- Food-drug interactions -- Racial groups; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2022.11.021
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: The systemic exposure of lazertinib was not significantly altered by food. Lazertinib can be administered without regard to food, enhancing the patient's adherence to treatment. Non-Asian and Asian patients showed similar systemic exposure both after single and multiple doses of lazertinib. No separate dose adjustment of lazertinib for race is required. Abstract: Objectives: Lazertinib is a potent, irreversible, brain-penetrant, mutant-selective, and wild type-sparing third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for advanced non-small cell lung cancer (NSCLC). The study aimed to evaluate the effects of food and race on the pharmacokinetics (PK) of lazertinib from a healthy volunteer trial and PK data from NSCLC patients with EGFR mutation. Materials and methods: An open-label, single-dose, two-period, single-sequence crossover study was conducted in healthy subjects with two race groups (non-Asian and Asian). Subjects orally received a single dose of lazertinib 240 mg in fasted and fed state (high-fat meal) in each period separated by a 21-day washout. An open-label, multicenter, phase 1/2 study was conducted in Asian and non-Asian patients with NSCLC. Patients were given oral lazertinib 20–320 mg once daily in fasted state continuously in 21-day cycles. PK parameters were evaluated using non-compartmental analysis. Results: A total of 24 healthy subjects (12 non-Asians and 12 Asians) and 52 NSCLC patients (22 non-Asians and 30 Asians) were evaluated. The change in the overall systemic exposure of lazertinib at fed state was less than 15%. Non-Asians showed 58–76% of the systemic exposure than Asians in healthy subjects. In contrast, there were no significant differences in systemic exposure by race both after single and multiple doses among NSCLC patients. Conclusion: Lazertinib can be taken with or without food considering the comparable systemic exposures related to food. Although effect of race was not consistent across studies, there was no evidence for dose adjustment based on race.