Etrumadenant (etruma), is an orally bioavailable, selective, A2a and A2b receptor antagonist that has demonstrated safety and clinical activity in solid tumors when combined with chemo/ immunotherapy
BACKGROUND
Etrumadenant (etruma), is an orally bioavailable, selective, A2a and A2b receptor antagonist that has demonstrated safety and clinical activity in solid tumors when combined with chemo/ immunotherapy
Etruma is a weak base with a pH-dependent solubility, potentially subject to absorption related drug interactions with acid reducing agents (ARAs)
Many patients on chemotherapy take ARAs, and food restrictions limit patient adherence; a preliminary food effect study indicated the effect of food on etruma PK was minimal
Across 11 studies, etruma has been co-administered with three types of ARAs: proton pump inhibitors (PPIs), histamine type 2 receptor antagonists (H2RAs), and antacids
OBJECTIVE
METHODS
PopPK analysis was conducted using nonlinear mixed effects modeling with the NONMEM software, version 7.5
PBPK analysis was conducted using Simcyp software
•PBPK model was developed from physiochemical, in vitro experimental and clinical datasets
•Predictive performance of the model was verified by comparing model PK predictions with the observed clinical PK data of etruma
Graphical and all other statistical analyses, including evaluation of NONMEM outputs, were performed using R version 4.2.3 for Windows
CONCLUSION: Supported by PopPK and PBPK modeling analyses
Acid reducing agents (PPIs, H2RAs, and Antacids) can be co-administered with etrumadenant
Etrumadenant can be taken with or without food
RESULTS: PopPK & PBPK Models adequately predict etrumadenant PK profiles for Fed State, or on PPI/other ARA agent
RESULTS: Forest plot of predicted exposure and maximum concentration ratios at steady state based on PopPK/PBPK simulation
