Boosting Osimertinib Blood Brain Barrier Penetration

Summary

The goal of this proof-of-concept clinical study is to determine the effect of combining osimertinib with febuxostat on cerebrospinal fluid concentrations of osimertinib in patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC). The main question it aims to answer is: what is the effect of combining osimertinib with the ABCG2 inhibitor febuxostat on cerebrospinal fluid to unbound plasma osimertinib concentration ratio in patients with EGFR mutated NSCLC without central nervous system (CNS) metastases and without the ABCG2 34G\>A single nucleotide polymorphism (SNP)?

Timeline

Start

2026-06

Primary completion

2027-06

Completion

2028-06

Publications

• Background Planchard D, Janne PA, Cheng Y, Yang JC, Yanagitani N, Kim SW, Sugawara S, Yu Y, Fan Y, Geater SL, Laktionov K, Lee CK, Valdiviezo N, Ahmed S, Maurel JM, Andrasina I, Goldman J, Ghiorghiu D, Rukazenkov Y, Todd A, Kobayashi K; FLAURA2 Investigators. Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2023 Nov 23;389(21):1935-1948. doi: 10.1056/NEJMoa2306434. Epub 2023 Nov 8.
• Background Veerman GDM, Boosman RJ, Jebbink M, Oomen-de Hoop E, van der Wekken AJ, Bahce I, Hendriks LEL, Croes S, Steendam CMJ, de Jonge E, Koolen SLW, Steeghs N, van Schaik RHN, Smit EF, Dingemans AC, Huitema ADR, Mathijssen RHJ. Influence of germline variations in drug transporters ABCB1 and ABCG2 on intracerebral osimertinib efficacy in patients with non-small cell lung cancer. EClinicalMedicine. 2023 Apr 13;59:101955. doi: 10.1016/j.eclinm.2023.101955. eCollection 2023 May.

Drugs

Indications