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# Model-driven scheduling of a novel anti-cancer prodrug administered subcutaneously

Anne Rodallec, Randy Lee, Jingming Cao, Sophie Marolleau, Julien Nicolas, Sébastien Benzekry

► To cite this version:

Anne Rodallec, Randy Lee, Jingming Cao, Sophie Marolleau, Julien Nicolas, et al. Model-driven scheduling of a novel anti-cancer prodrug administered subcutaneously. PAGE, Jun 2025, Thessalonic, Greece. hal-05241394

HAL Id: hal-05241394

https://hal.science/hal-05241394v1

Submitted on 5 Sep 2025

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Distributed under a Creative Commons Attribution 4.0 International License
# Model-driven scheduling of a novel anti-cancer prodrug administered subcutaneously

Anne Rodallec¹, Randy Lee¹, Jingming Cao², Sophie Marolleau¹, Julien Nicolas²*, Sébastien Benzekry¹*

¹COMPO Unit, Inria Sophia Antipolis-Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, Aix Marseille University UM105, Marseille, France
² Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400 Orsay, France

## MOTIVATIONS & OBJECTIVES

Chemotherapy is a cornerstone in the treatment of solid tumors but is associated with high toxicities and patient discomfort. New formulations with **improved pharmacokinetics** (PK) are being developed to **increase efficacy** and to **reduce toxicities**. These formulations present greater: exposure, tumor uptake, lipophilicity and maximum tolerated dose, creating opportunities for broader therapeutic index.

## EXPERIMENTAL BACKGROUND

### Nanocarrier

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Schematic representation of the water-soluble polymer prodrug of paclitaxel (Ptx-PAAm) administered subcutaneously (SC) [1]

### Software

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### Pharmacokinetic and Pharmacodynamic data

Data PK n=4

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Data PD n=9

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## RESULTS

### Final structural PK/PD Model

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### Diagnostic plots for the training (A) and test (B) data set

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### In vivo results and Model Validation

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(A) Tumor growth (means ± SD, n = 10 per group). (B) Overall survival. Groups 5 and 7 are perfectly overlaid and meet Group 2 at the end of experiment. (C) Relative body weight change of mice as a function of time after SC Ptx-PAAm injection following specific scheduling. The values are expressed as the means ± SD (n = 10). (D) Median prediction (thick line) and individual observations (thin lines) of tumor growth for all treatment groups. Treatment groups have been schematized using arrows whose thickness is proportional to the dose. Horizontal arrows represent daily administration.

## ACKNOWLEDGMENTS

This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (Grant agreement No. 771829).

## OUTLINE
New PK profile of Nanocarriers require dose regimen optimization: PK/PD modeling

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