ArticleClinical pharmacology and therapeutics2020
PK/PD Mediated Dose Optimization of Emactuzumab, a CSF1R Inhibitor, in Patients With Advanced Solid Tumors and Diffuse-Type Tenosynovial Giant Cell Tumor.
Article in Clinical pharmacology and therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Update on Tenosynovial Giant Cell Tumor, an Inflammatory Arthritis With Neoplastic Features.Frontiers in immunology · 2022Pooled it
- TANGENT study design: a phase III, randomized study of emactuzumab for the treatment of tenosynovial giant cell tumors.Future oncology (London, England) · 2026Trial
- Bilateral Localized-Tenosynovial Giant Cell Tumor of the Knee: Case Report and Review.Journal of clinical medicine · 2026Article
- Localized and diffuse tenosynovial giant cell tumor: real-world results from a patient observational registry.Future oncology (London, England) · 2025Observational
- Treatment Modalities for Refractory-Recurrent Tenosynovial Giant Cell Tumor (TGCT): An Update.Medicina (Kaunas, Lithuania) · 2024Review
- Article
- Anti-CSF-1R emactuzumab in combination with anti-PD-L1 atezolizumab in advanced solid tumor patients naïve or experienced for immune checkpoint blockade.Journal for immunotherapy of cancer · 2022Article
- Clinical Development of Colony-Stimulating Factor 1 Receptor (CSF1R) Inhibitors.Journal of immunotherapy and precision oncology · 2021Review
- Phase Ib study of anti-CSF-1R antibody emactuzumab in combination with CD40 agonist selicrelumab in advanced solid tumor patients.Journal for immunotherapy of cancer · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted biological therapies may achieve maximal therapeutic efficacy at doses below the maximum tolerated dose (MTD); therefore, the search for the MTD in clinical studies may not be ideal for these agents. Emactuzumab is an investigational monoclonal antibody that binds to and inhibits the activation of the cell surface colony-stimulating factor-1 receptor. Here, we show how modeling target-mediated drug disposition coupled with pharmacodynamic end points was used to optimize the dose of emactuzumab without defining an MTD. The model could be used to recommend doses across different disease indications. The approach recommended an optimal biological dose of emactuzumab for dosing every 2 weeks (q2w) ≥ 900 mg, approximately three-fold lower than the highest dose tested clinically. The model predicted that emactuzumab doses ≥ 900 mg q2w would achieve target saturation in excess of 90% over the entire dosing cycle. Subsequently, a dose of 1,000 mg q2w was used in the extension phase of a phase I study of emactuzumab in patients with advanced solid tumors or diffuse-type tenosynovial giant cell tumor. Clinical data from this study were consistent with model predictions. The model was also used to predict the optimum dose of emactuzumab for use with dosing every 3 weeks, enabling dosing flexibility with respect to comedications. In summary, this work demonstrates the value of quantitative clinical pharmacology approaches to dose selection in oncology as opposed to traditional MTD methods.
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