Identification of predictive biomarkers and dose optimization for camrelizumab combined with apatinib in the treatment of advanced hepatocellular carcinoma: a quantitative systems pharmacology approach.

[INTRODUCTION] The combination of camrelizumab and apatinib represents a promising treatment strategy for patients with advanced hepatocellular carcinoma (aHCC). However, the specific patient populations that may benefit from this combination therapy, as well as the changes in efficacy after adjusting the medication regimen to avoid serious adverse reactions, remain uncertain.

[METHODS] We employ a quantitative systems pharmacology (QSP) approach to address these significant clinical issues. A QSP model is established by integrating pharmacokinetic data of camrelizumab and apatinib, generating a virtual patient cohort for rapid and reliable virtual clinical studies.

[RESULTS] Ultimately, our model identifies the pre-treatment CD8+/Treg ratio, CD4+/Treg ratio, and the density of myeloid-derived suppressor cells (MDSCs) as key predictive biomarkers. Furthermore, through computer-simulated clinical trials, we find that reducing the dose of apatinib in combination therapy to 125 mg can still achieve therapeutic effects comparable to the original dose.

[DISCUSSION] These findings provide valuable insights for future drug development and clinical trial design.