ArticleScientific reports2019
A QSP Model for Predicting Clinical Responses to Monotherapy, Combination and Sequential Therapy Following CTLA-4, PD-1, and PD-L1 Checkpoint Blockade.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Recent applications of quantitative systems pharmacology and machine learning models across diseases.Journal of pharmacokinetics and pharmacodynamics · 2022Pooled it
- Virtual clinical trials of anti-PD-1 and anti-CTLA-4 immunotherapy in advanced hepatocellular carcinoma using a quantitative systems pharmacology model.Journal for immunotherapy of cancer · 2022Trial
- Quantitative Systems Pharmacology (QSP): Bridging Biology and Mechanism with Clinical Drug Development Decisions.Journal of clinical pharmacology · 2026Review
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Quantitative systems pharmacology model of B cell immune response in mouse.Frontiers in immunology · 2026Article
- A Step-by-Step Workflow for Performing In Silico Clinical Trials With Nonlinear Mixed Effects Models.CPT: pharmacometrics & systems pharmacology · 2025Article
- A Proxy-guided Workflow for Virtual Population Development.The AAPS journal · 2025Article
- Leveraging quantitative systems pharmacology modeling for elranatamab regimen optimization in relapsed or refractory multiple myeloma.NPJ systems biology and applications · 2025Article
- Using mathematical modelling and AI to improve delivery and efficacy of therapies in cancer.Nature reviews. Cancer · 2025Review
- Mathematical modeling of the synergetic effect between radiotherapy and immunotherapy.Mathematical biosciences and engineering : MBE · 2025Article
- Predicting survival in prospective clinical trials using weakly-supervised QSP.NPJ precision oncology · 2025Article
- A Multiple-Model-Informed Drug-Development Approach for Optimal Regimen Selection of an Oncolytic Virus in Combination With Pembrolizumab.CPT: pharmacometrics & systems pharmacology · 2025Article
- An overview of immunotoxicity in drug discovery and development.Toxicology letters · 2025Review
- A Framework for Quantitative Systems Pharmacology Model Execution.Handbook of experimental pharmacology · 2025Review
- Quantitative Systems Pharmacology Modeling in Immuno-Oncology: Hypothesis Testing, Dose Optimization, and Efficacy Prediction.Handbook of experimental pharmacology · 2025Review
- Case report and literature review: tislelizumab combined with lenvatinib and polymeric micellar paclitaxel for thymic squamous cell carcinoma.Frontiers in immunology · 2025Review
- A mechanistic quantitative systems pharmacology model platform for translational efficacy evaluation and checkpoint combination design of bispecific immuno-modulatory antibodies.Frontiers in pharmacology · 2025Article
- Assessing tumor volumetric reduction with consideration for setup errors based on mathematical tumor model and microdosimetric kinetic model in single-isocenter VMAT for brain metastases.Physical and engineering sciences in medicine · 2024Article
- An industry perspective on current QSP trends in drug development.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Assessing the performance of QSP models: biology as the driver for validation.Journal of pharmacokinetics and pharmacodynamics · 2024Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Over the past decade, several immunotherapies have been approved for the treatment of melanoma. The most prominent of these are the immune checkpoint inhibitors, which are antibodies that block the inhibitory effects on the immune system by checkpoint receptors, such as CTLA-4, PD-1 and PD-L1. Preclinically, blocking these receptors has led to increased activation and proliferation of effector cells following stimulation and antigen recognition, and subsequently, more effective elimination of cancer cells. Translation from preclinical to clinical outcomes in solid tumors has shown the existence of a wide diversity of individual patient responses, linked to several patient-specific parameters. We developed a quantitative systems pharmacology (QSP) model that looks at the mentioned checkpoint blockade therapies administered as mono-, combo- and sequential therapies, to show how different combinations of specific patient parameters defined within physiological ranges distinguish different types of virtual patient responders to these therapies for melanoma. Further validation by fitting and subsequent simulations of virtual clinical trials mimicking actual patient trials demonstrated that the model can capture a wide variety of tumor dynamics that are observed in the clinic and can predict median clinical responses. Our aim here is to present a QSP model for combination immunotherapy specific to melanoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.