ArticleInvestigational new drugs2018
Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose.
Article in Investigational new drugs, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Population Pharmacokinetics of MCLA-128, a HER2/HER3 Bispecific Monoclonal Antibody, in Patients with Solid Tumors.Clinical pharmacokinetics · 2020Trial
- Targeting Tumor Microenvironment-Derived NRG1-HER2/3 Signaling with Zenocutuzumab Restores Sensitivity to AR Inhibition in PTEN Wild-type Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Overcoming resistance to antibody-drug conjugates: from mechanistic insights to cutting-edge strategies.Journal of hematology & oncology · 2025Review
- Structure and function of therapeutic antibodies approved by the US FDA in 2024.Antibody therapeutics · 2025Review
- Zenocutuzumab: First Approval.Drugs · 2025Review
- Breast Cancer Treatment Strategies Targeting the Tumor Microenvironment: How to Convert "Cold" Tumors to "Hot" Tumors.International journal of molecular sciences · 2024Review
- HER3-targeted therapy: the mechanism of drug resistance and the development of anticancer drugs.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Bispecific Antibodies in Lung Cancer: A State-of-the-Art Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Mechanistically Weighted Metric to Predict In Vivo Antibody-Receptor Occupancy: An Analytical Approach.The Journal of pharmacology and experimental therapeutics · 2023Article
- Review
- Review of the Existing Translational Pharmacokinetics Modeling Approaches Specific to Monoclonal Antibodies (mAbs) to Support the First-In-Human (FIH) Dose Selection.International journal of molecular sciences · 2022Review
- Targeted Approaches to HER2-Low Breast Cancer: Current Practice and Future Directions.Cancers · 2022Review
- Recent Advances in Translational Pharmacokinetics and Pharmacodynamics Prediction of Therapeutic Antibodies Using Modeling and Simulation.Pharmaceuticals (Basel, Switzerland) · 2022Review
- From Anti-HER-2 to Anti-HER-2-CAR-T Cells: An Evolutionary Immunotherapy Approach for Gastric Cancer.Journal of inflammation research · 2022Review
- Recent advances and challenges of bispecific antibodies in solid tumors.Experimental hematology & oncology · 2021Review
- Bioanalysis in the Age of New Drug Modalities.The AAPS journal · 2021Review
- Bispecific antibodies targeting dual tumor-associated antigens in cancer therapy.Journal of cancer research and clinical oncology · 2020Review
- Bispecific antibodies: a mechanistic review of the pipeline.Nature reviews. Drug discovery · 2019Review
- Article
- Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction MCLA-128 is a bispecific monoclonal antibody targeting the HER2 and HER3 receptors. Pharmacokinetics (PK) and pharmacodynamics (PD) of MCLA-128 have been evaluated in preclinical studies in cynomolgus monkeys and mice. The aim of this study was to characterize the PK and PD of MCLA-128 and to predict a safe starting dose and efficacious clinical dose for the First-In-Human study. Methods A PK-PD model was developed based on PK data from cynomolgus monkeys and tumor growth data from a mouse JIMT-1 xenograft model. Allometric scaling was used to scale PK parameters between species. Simulations were performed to predict the safe and efficacious clinical dose, based on AUCs, receptor occupancies and PK-PD model simulations. Results MCLA-128 PK in cynomolgus monkeys was described by a two-compartment model with parallel linear and nonlinear clearance. The xenograft tumor growth model consisted of a tumor compartment with a zero-order growth rate and a first-order dying rate, both affected by MCLA-128. Human doses of 10 to 480 mg q3wk were predicted to show a safety margin of >10-fold compared to the cynomolgus monkey AUC at the no-observed-adverse-effect-level (NOAEL). Doses of ≥360 mg resulted in predicted receptor occupancies above 99% (C
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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.