ArticleThe AAPS journal2016
Preclinical to Clinical Translation of Antibody-Drug Conjugates Using PK/PD Modeling: a Retrospective Analysis of Inotuzumab Ozogamicin.
Article in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
- Quantitative Systems Pharmacology Model for TROP-2 Targeted Antibody-Drug Conjugate in Triple-Negative Breast Cancer.bioRxiv : the preprint server for biology · 2026Article
- Clinical Pharmacology and Translational Science Considerations in the Development of Dual-Payload Antibody Drug Conjugates.Clinical and translational science · 2026Review
- Industry Practices in Monoclonal Antibody Tissue Biodistribution Assessment: An IQ Consortium Cross-Industry Survey of Current Approaches and Emerging Trends.The AAPS journal · 2026Article
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- Modernizing Preclinical Drug Development: The Role of New Approach Methodologies.ACS pharmacology & translational science · 2025Review
- Using mathematical modelling and AI to improve delivery and efficacy of therapies in cancer.Nature reviews. Cancer · 2025Review
- Towards a platform quantitative systems pharmacology (QSP) model for preclinical to clinical translation of antibody drug conjugates (ADCs).Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Nanoparticle-Mediated Drug Delivery Systems for Precision Targeting in Oncology.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Translation of the efficacy of antibody-drug conjugates from preclinical to clinical using a semimechanistic PK/PD model: A case study with RC88.Clinical and translational science · 2023Article
- 'Targeting' Improved Outcomes with Antibody-Drug Conjugates in Non-Small Cell Lung Cancer-An Updated Review.Current oncology (Toronto, Ont.) · 2023Review
- Pharmacokinetics and Pharmacodynamics of Antibody-Drug Conjugates Administered via Subcutaneous and Intratumoral Routes.Pharmaceutics · 2023Article
- Inotuzumab ozogamicin in B-cell precursor acute lymphoblastic leukemia: efficacy, toxicity, and practical considerations.Frontiers in immunology · 2023Review
- Development of and insights from systems pharmacology models of antibody-drug conjugates.CPT: pharmacometrics & systems pharmacology · 2022Review
- Quantitative systems pharmacology modeling provides insight into inter-mouse variability of Anti-CTLA4 response.CPT: pharmacometrics & systems pharmacology · 2022Article
- Algorithmic multiscale analysis for the FcRn mediated regulation of antibody PK in human.Scientific reports · 2022Article
- Targeting Engineered Nanoparticles for Breast Cancer Therapy.Pharmaceutics · 2021Review
- Article
- Reduction of quantitative systems pharmacology models using artificial neural networks.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- The clinical development of antibody-drug conjugates - lessons from leukaemia.Nature reviews. Clinical oncology · 2021Review
- Mechanistic Modeling of Intra-Tumor Spatial Distribution of Antibody-Drug Conjugates: Insights into Dosing Strategies in Oncology.Clinical and translational science · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model was used for preclinical to clinical translation of inotuzumab ozogamicin, a CD22-targeting antibody-drug conjugate (ADC) for B cell malignancies including non-Hodgkin's lymphoma (NHL) and acute lymphocytic leukemia (ALL). Preclinical data was integrated in a PK/PD model which included (1) a plasma PK model characterizing disposition and clearance of inotuzumab ozogamicin and its released payload N-Ac-γ-calicheamicin DMH, (2) a tumor disposition model describing ADC diffusion into the tumor extracellular environment, (3) a cellular model describing inotuzumab ozogamicin binding to CD22, internalization, intracellular N-Ac-γ-calicheamicin DMH release, binding to DNA, or efflux from the tumor cell, and (4) tumor growth and inhibition in mouse xenograft models. The preclinical model was translated to the clinic by incorporating human PK for inotuzumab ozogamicin and clinically relevant tumor volumes, tumor growth rates, and values for CD22 expression in the relevant patient populations. The resulting stochastic models predicted progression-free survival (PFS) rates for inotuzumab ozogamicin in patients comparable to the observed clinical results. The model suggested that a fractionated dosing regimen is superior to a conventional dosing regimen for ALL but not for NHL. Simulations indicated that tumor growth is a highly sensitive parameter and predictive of successful outcome. Inotuzumab ozogamicin PK and N-Ac-γ-calicheamicin DMH efflux are also sensitive parameters and would be considered more useful predictors of outcome than CD22 receptor expression. In summary, a multiscale, mechanism-based model has been developed for inotuzumab ozogamicin, which can integrate preclinical biomeasures and PK/PD data to predict clinical response.
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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.