Effects of food and esomeprazole on pharmacokinetics of sevabertinib

Background:

Sevabertinib (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 human epidermal growth factor receptor 2–activating mutations. Sevabertinib is a high-permeability compound with low pH-dependent aqueous solubility. A clinical study was performed to evaluate the pharmacokinetics (PK) of sevabertinib when administered under fasted conditions or following a highor low-fat meal (NCT06378658). The effect of the proton pump inhibitor (PPI) esomeprazole was also evaluated.

Objectives:

Describe the effect of food and esomeprazole on the PK of sevabertinib.

Methods:

This was an open-label, randomized, crossover study to investigate the effect of food or an acid-reducing agent on the PK of sevabertinib in 21 healthy volunteers. A single dose of sevabertinib 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 sevabertinib on day 4 following a light meal. Safety and tolerability were closely monitored throughout the study.

Results:

A high-fat meal reduced sevabertinib area under the curve (AUC) and maximum observed drug concentration (Cmax) by 28% and 56%, respectively, compared with fasted conditions. A low-fat meal reduced sevabertinib AUC and Cmax by 16% and 28%, respectively, compared with fasted conditions. Sevabertinib AUC was 14% lower following a high-fat meal compared with a low-fat meal. Co-administration of esomeprazole did not affect the mean AUC of sevabertinib. Sevabertinib was safe and well tolerated in healthy participants.

Discussion:

Sevabertinib exposure was decreased slightly when administered with food compared with fasted conditions, with no clinically relevant difference between meal types. The lack of a clinically relevant effect of esomeprazole suggests that acid-reducing agents do not meaningfully alter sevabertinib exposure.

Conclusions:

These findings support administration of sevabertinib with food in clinical trials and indicate that sevabertinib can be administered with proton pump inhibitors without clinically relevant impact on exposure.

Funding: Bayer AG.

Prior Presentations:

Presented at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting 2025, May 28-31, Washington, DC.