ArticleCPT: pharmacometrics & systems pharmacology2023
A model-based approach leveraging in vitro data to support dose selection from the outset: A framework for bispecific antibodies in immuno-oncology.
Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed, 4 citations in OpenAlex.
- Foundational Principles for the Quantitative Translation of T-Cell Therapeutics for Hematologic Malignancies and Immunology.Clinical pharmacology and therapeutics · 2026Review
- Combining mathematical modeling,Frontiers in pharmacology · 2024Article
- Role of pharmacometrics and systems pharmacology in facilitating efficient dose optimization in oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
- A model-based approach leveraging in vitro data to support dose selection from the outset: A framework for bispecific antibodies in immuno-oncology.CPT: pharmacometrics & systems pharmacology · 2023Article
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
FAP-4-1BBL is a bispecific antibody exerting 4-1BB-associated T-cell activation only while simultaneously bound to the fibroblast activation protein (FAP) receptor, expressed on the surface of cancer-associated fibroblasts. The trimeric complex formed when FAP-4-1BBL is simultaneously bound to FAP and 4-1BB represents a promising mechanism to achieve tumor-specific 4-1BB stimulation. We integrated in vitro data with mathematical modeling to characterize the pharmacology of FAP-4-1BBL as a function of trimeric complex formation when combined with the T-cell engager cibisatamab. This relationship was used to prospectively predict a range of clinical doses where trimeric complex formation is expected to be at its maximum. Depending on the dosing schedule and FAP-4-1BBL plasma: tumor distribution, doses between 2 and 145 mg could lead to maximum trimeric complex formation in the clinic. Due to the expected variability in both pharmacokinetic and FAP expression in the patient population, we predict that detecting a clear dose-response relationship would remain difficult without a large number of patients per dose level, highlighting that mathematical modeling techniques based on in vitro data could aid dose selection.
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Registered trials
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