Generating immunogenomic data-guided virtual patients using a QSP model to predict response of advanced NSCLC to PD-L1 inhibition

Generating realistic virtual patients from a limited amount of patient data is one of the major challenges for quantitative systems pharmacology modeling in immuno-oncology. Quantitative systems pharmacology (QSP) is a mathematical modeling methodology that integrates mechanistic knowledge of biological systems to investigate dynamics in a whole system during disease progression and drug treatment. In the present analysis, we parameterized our previously published QSP model of the cancer-immunity cycle to non-small cell lung cancer (NSCLC) and generated a virtual patient cohort to predict clinical response to PD-L1 inhibition in NSCLC. The virtual patient generation was guided by immunogenomic data from iAtlas portal and population pharmacokinetic data of durvalumab, a PD-L1 inhibitor. With virtual patients generated following the immunogenomic data distribution, our model predicted a response rate of 18.6% (95% bootstrap confidence interval: 13.3-24.2%) and identified CD8/Treg ratio as a potential predictive biomarker in addition to PD-L1 expression and tumor mutational burden. We demonstrated that omics data served as a reliable resource for virtual patient generation techniques in immuno-oncology using QSP models.

Automated summary

QSP models can be used to generate virtual patients and predict drug response. This study used immunogenomic data and pharmacokinetic data to generate virtual patients for non-small cell lung cancer (NSCLC) and predicted clinical response to PD-L1 inhibition.