Leveraging a QSP Platform for Prediction of Clinical Efficacy and Safety Biomarkers in Immuno-Oncology Combination Therapy.

IO Simulator is a Quantitative Systems Pharmacology platform implementing a mechanistic model of solid tumor-immune system interactions and the action of standard immuno-oncology drugs. Using a tarlatamab case study, we demonstrate how IO Simulator predicts combination therapy efficacy and cytokine biomarkers, which can be statistically related to the risk of cytokine release syndrome (CRS). This allows patient stratification and identification of doses that maximize efficacy without a substantial increase in cytokine release.