ArticleClinical pharmacology and therapeutics2022
Semimechanistic Physiologically-Based Pharmacokinetic/Pharmacodynamic Model Informing Epcoritamab Dose Selection for Patients With B-Cell Lymphomas.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 31 citations in OpenAlex.
- Teclistamab Dosing in Responders: Modeling and Simulation Results from the MajesTEC-1 Study in Relapsed/Refractory Multiple Myeloma.Targeted oncology · 2025Trial
- Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.Clinical pharmacokinetics · 2025Trial
- An In Vitro Quantitative Systems Pharmacology Platform for Characterizing CD3-Bispecific Antibody-Mediated T-Cell Activation and Tumor Cell Cytotoxicity.The AAPS journal · 2026Article
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Overview of Quantitative Clinical Pharmacology for T-Cell Engaging Bispecific Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Using Virtual Patients to Evaluate Dosing Strategies for Bispecifics With a Bell-Shaped Efficacy Curve.CPT: pharmacometrics & systems pharmacology · 2025Article
- Review
- New bispecific antibodies in diffuse large B-cell lymphoma.Haematologica · 2025Review
- CD20×CD3 Bispecific Antibodies in B-NHL: A Review of Translational Science, Pharmacokinetics, Pharmacodynamics, and Dose Strategy in Clinical Research.Clinical and translational science · 2025Review
- A Novel Two-Part Mixture Model for the Incidence and Time Course of Cytokine Release Syndrome After Elranatamab Dosing in Multiple Myeloma Patients.Clinical pharmacology and therapeutics · 2025Article
- Optimal Dosing Regimen for Epcoritamab, a Subcutaneous Bispecific Antibody, in Relapsed or Refractory Large B-Cell Lymphoma.Clinical pharmacology and therapeutics · 2025Article
- Clinical Pharmacology of Cytokine Release Syndrome with T-Cell-Engaging Bispecific Antibodies: Current Insights and Drug Development Strategies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Bispecific Antibodies for Lymphoid Malignancy Treatment.Cancers · 2024Review
- Translational findings support regimen selection for first-in-human study of ubamatamab (MUC16 × CD3 bispecific antibody) in patients with recurrent ovarian cancer.Clinical and translational science · 2024Article
- Optimizing Clinical Translation of Bispecific T-cell Engagers through Context Unification with a Quantitative Systems Pharmacology Model.Clinical pharmacology and therapeutics · 2024Article
- Moving the needle for oncology dose optimization: A call for action.CPT: pharmacometrics & systems pharmacology · 2024Article
- Moving the needle for oncology dose optimization: A call for action.Clinical and translational science · 2024Article
- Development of bispecific T cell engagers: harnessing quantitative systems pharmacology.Trends in pharmacological sciences · 2023Review
- Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epcoritamab is a CD3xCD20 bispecific antibody (bsAb) that induces T-cell-mediated cytotoxicity against CD20-positive B cells. Target engagement and crosslinking of CD3 and CD20 (trimer formation) leads to activation and expansion of T cells and killing of malignant B cells. The primary objective of the dose-escalation part of the phase I/II trial of epcoritamab was to determine the maximum tolerated dose, recommended phase II dose (RP2D), or both. For bsAbs, high target saturation can negatively affect trimer formation. The unique properties and mechanisms of action of bsAbs require novel pharmacokinetic (PK) modeling methods to predict clinical activity and inform RP2D selection. Traditional PK/pharmacodynamic (PD) modeling approaches are inappropriate because they may not adequately predict exposure-response relationships. We developed a semimechanistic, physiologically-based PK/PD model to quantitatively describe biodistribution, trimer formation, and tumor response using preclinical, clinical PK, biomarker, tumor, and response data from the dose-escalation part of the phase I/II trial. Clinical trial simulations were performed to predict trimer formation and tumor response in patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Model-predicted trimer formation plateaued at doses of 48 to 96 mg. Simulation results suggest that the 48-mg dose may achieve optimal response rates in DLBCL and FL. Exposure-safety analyses showed a flat relationship between epcoritamab exposure and risk of cytokine release syndrome in the dose range evaluated. This novel PK/PD modeling approach guided selection of 48 mg as the RP2D and provides a framework that may be applied to other CD3 bsAbs.
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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.