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

Area of Science:

• Pharmacology
• Oncology
• Clinical Pharmacology

Background:

• Osimertinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) targeting specific mutations in non-small cell lung cancer (NSCLC).
• Understanding the pharmacokinetics (PK) of osimertinib in diverse populations is crucial for optimizing treatment.
• Previous studies have established the global PK profile of osimertinib.

Purpose of the Study:

• To characterize the pharmacokinetics (PK) and safety of osimertinib in Chinese patients with advanced or metastatic EGFR-mutated NSCLC.
• To evaluate the PK profile following single and multiple doses of osimertinib (40 mg and 80 mg once daily).
• To compare the PK of osimertinib in Chinese patients with existing global data.

Main Methods:

• A clinical study (NCT02529995) involving Chinese patients aged ≥18 years with EGFR-TKI-sensitizing NSCLC who progressed on prior EGFR-TKI therapy.
• Pharmacokinetic parameters were assessed after single and multiple daily doses of 40 mg or 80 mg osimertinib.
• Safety and efficacy (objective response rate) were evaluated alongside PK assessments.

Main Results:

• Osimertinib exhibited a flat pharmacokinetic profile with a low maximum-minimum plasma concentration ratio at steady state.
• The objective response rate was 47% in the 40 mg cohort and 75% in the 80 mg cohort.
• Adverse events were generally manageable, with serious adverse events reported in 26% of patients. One patient experienced an AE leading to death.

Conclusions:

• Osimertinib's PK in Chinese patients is well-characterized and consistent with the global population.
• The findings support the established once-daily 80 mg dose of osimertinib for treating Chinese patients with EGFR-mutated NSCLC.
• The safety and efficacy observed align with previous global studies, reinforcing its therapeutic value.