PI-065 - EFFECT OF FOOD AND ESOMEPRAZOLE ON THE PHARMACOKINETICS (PK) OF BAY 2927088

B. Brennan¹, M. Damaske², F. Hafner³, U. Muenster³, A. Lender³, J. Joseph³, S. Reif², S. Prendergast⁴, P. Lienau², B. Ploeger², C. Chen⁵; ¹Bayer, Whippany, NJ, USA, ²Bayer, Berlin, Germany, ³Bayer, Wuppertal, Germany, ⁴Bayer, Reading, United Kingdom, ⁵Bayer, Whippany, USA.

Background: BAY 2927088 is an oral reversible tyrosine kinase inhibitor being developed for treatment of adult patients with unresectable or metastatic non-small cell lung cancer harboring HER2 activating mutations. BAY 2927088 is a high permeability compound with low pH dependent aqueous solubility. A clinical study was performed to evaluate the PK of BAY 2927088 when administered under fasted conditions or following a high- or low-fat meal. The effect of the proton pump inhibitor (PPI) esomeprazole was also evaluated.

Methods: This was an open label, randomized, crossover study to investigate the effect of food or an acid reducing agent on the PK of BAY 2927088 in 18 healthy volunteers. A single dose of BAY 2927088 was administered under fasted conditions or following a high calorie/fat meal or a low calorie/fat meal. Esomeprazole was administered for 5 days with a single dose of BAY 2927088 on Day 4 following a light meal. Safety and tolerability were closely monitored throughout the study.

Results: A high-fat meal reduced BAY 2927088 AUC and Cmax by 28% and 56%, respectively, compared to fasted conditions. A low-fat meal reduced BAY 2927088 AUC and Cmax by 16% and 28%, respectively, compared to fasted conditions. BAY 2927088 AUC was 14% lower following a high fat meal vs. a low-fat meal. BAY 2927088 AUC was about 10% lower when co-administered with esomeprazole. BAY 2927088 was safe and well tolerated in healthy participants.

Conclusion: BAY 2927088 exposure was decreased slightly when administered with food compared to fasted with no clinically relevant difference between meal types. This supports BAY 2927088 administration with food in clinical trials. Esomeprazole did not have a clinically relevant impact on exposure so BAY 2927088 can be administered with acid reducing agents.