ORIGINAL RESEARCH article
Front. Immunol.
Sec. Systems Immunology
This article is part of the Research TopicModeling the Immune System: from PK/PD to Systems ImmunologyView all 10 articles
Identification of Predictive Biomarkers and Dose Optimization for Camrelizumab Combined with Apatinib in the Treatment of Advanced Hepatocellular Carcinoma: A Quantitative Systems Pharmacology Approach
Provisionally accepted
- 1Department of pharmacy, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China., Fuzhou, Fujian Province, China
- 2Pharmacy Department, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Medical College, Chongqing University, Chongqing, China
- 3Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 4Department of Pharmacy, Fujian Medical University Union Hospital, Fujian, China
- 5Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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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. 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. Ultimately, our model identifies the pretreatment 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. These findings provide valuable insights for future drug development and clinical trial design.
Keywords: advancedhepatocellular carcinoma4, apatinib3, biomarkers5, Camrelizumab2, dose optimization6, quantitative systems pharmacology1
Received: 24 Apr 2025; Accepted: 30 Jan 2026.
Copyright: © 2026 Huang, Tu, Li, Wang, Zhou, Jiao and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zheng Jiao
Lin Yang
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