Trial reportClinical pharmacology and therapeutics2012
Semi-mechanistic population pharmacokinetic model of multivalent trastuzumab emtansine in patients with metastatic breast cancer.
Trial report in Clinical pharmacology and therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 51 citations in OpenAlex.
- Covariate analysis of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate, based on first-in-human study.CPT: pharmacometrics & systems pharmacology · 2022Trial
- Applications of Pharmacometrics in Antibody-Drug Conjugate Development.Pharmaceutics · 2026Review
- Review
- Using mathematical modelling and AI to improve delivery and efficacy of therapies in cancer.Nature reviews. Cancer · 2025Review
- Application of Pharmacometrics in Advancing the Clinical Research of Antibody-Drug Conjugates: Principles and Modeling Strategies.Clinical pharmacokinetics · 2024Review
- A Sequential Population Pharmacokinetic Model of Zilovertamab Vedotin in Patients with Hematologic Malignancies Extrapolated to the Pediatric Population.Clinical pharmacokinetics · 2024Article
- Integrated multiple analytes and semi-mechanistic population pharmacokinetic model of tusamitamab ravtansine, a DM4 anti-CEACAM5 antibody-drug conjugate.Journal of pharmacokinetics and pharmacodynamics · 2022Article
- Mechanistic Modeling of Intra-Tumor Spatial Distribution of Antibody-Drug Conjugates: Insights into Dosing Strategies in Oncology.Clinical and translational science · 2021Article
- Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.Clinical pharmacokinetics · 2019Review
- Antibody-Drug Conjugates: Pharmacokinetic/Pharmacodynamic Modeling, Preclinical Characterization, Clinical Studies, and Lessons Learned.Clinical pharmacokinetics · 2018Review
- Development of a Translational Physiologically Based Pharmacokinetic Model for Antibody-Drug Conjugates: a Case Study with T-DM1.The AAPS journal · 2017Article
- A Mechanism-Based PK/PD Model for Hematological Toxicities Induced by Antibody-Drug Conjugates.The AAPS journal · 2017Article
- Application of a PK-PD Modeling and Simulation-Based Strategy for Clinical Translation of Antibody-Drug Conjugates: a Case Study with Trastuzumab Emtansine (T-DM1).The AAPS journal · 2017Article
- Integrated Two-Analyte Population Pharmacokinetic Model for Antibody-Drug Conjugates in Patients: Implications for Reducing Pharmacokinetic Sampling.CPT: pharmacometrics & systems pharmacology · 2016Article
- Cell-specific biomarkers and targeted biopharmaceuticals for breast cancer treatment.Cell proliferation · 2016Review
- Determination of Cellular Processing Rates for a Trastuzumab-Maytansinoid Antibody-Drug Conjugate (ADC) Highlights Key Parameters for ADC Design.The AAPS journal · 2016Article
- Application of Pharmacokinetic-Pharmacodynamic Modeling and Simulation for Antibody-Drug Conjugate Development.Pharmaceutical research · 2015Review
- Preclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates.Pharmaceutical research · 2015Review
- Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.The AAPS journal · 2015Review
- Mechanism-Based Pharmacokinetic/Pharmacodynamic Model for THIOMAB™ Drug Conjugates.Pharmaceutical research · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate (ADC) composed of multiple molecules of the antimicrotubule agent DM1 linked to trastuzumab, a humanized anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody. Pharmacokinetics data from phase I (n = 52) and phase II (n = 111) studies in HER2-positive metastatic breast cancer patients show a shorter terminal half-life for T-DM1 than for total trastuzumab (TTmAb). In this work, we translated prior preclinical modeling in monkeys to develop a semi-mechanistic population pharmacokinetics model to characterize T-DM1 and TTmAb concentration profiles. A series of transit compartments with the same disposition parameters was used to describe the deconjugation process from higher to lower drug-to-antibody ratios (DARs). The structure could explain the shorter terminal half-life of T-DM1 relative to TTmab. The final model integrates prior knowledge of T-DM1 DARs from preclinical studies and could provide a platform for understanding and characterizing the pharmacokinetics of other ADC systems.
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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.