SMARTc

La Timone

Joseph Ciccolini

Platform manager

Anne Rodallec

Lecturer and researcher

Raphaëlle Fanciullino

Teacher-Researcher-Hospital Practitioner

Sarah Giacometti

Technician

The SMARTc platform specializes in optimizing the efficacy/toxicity balance of anti-cancer drugs in clinical and preclinical settings, through pharmacokinetic optimization. Several strategies are implemented, such as pharmacogenetic studies, the use of mathematical models to define the administration and/or combination modalities of therapies, or the synthesis of nanomedicines enabling better targeting and longer residence in the body.

The SMARTc platform, located on the Timone Health Campus (Faculty of Pharmacy and Timone University Hospital), The aim is to optimize the efficacy/toxicity balance of anti-cancer drugs. SMARTc is built around a group of pharmacists and modelers, working with pharmacological and clinical researchers in a laboratory equipped and approved by veterinary services to conduct experimental studies (in vitro, in vivo) with a strong specialization in drug pharmacokinetics.
SMARTc is also supported by the APHM Biogenopôle, a platform for the bioanalytical assay of anti-cancer drugs (small molecules, biotherapies, ADCs) and their metabolites in an ISO15189-certified environment. This expertise covers the full range of treatments, from cytotoxic chemotherapy to oral targeted therapies and biologics, including immunotherapy products, at both preclinical and clinical development stages.

This includes:

- Develop dose adjustment algorithms including biomarkers of interest.
- Identify genetic or phenotypic covariates impacting drug PK/PD relationships.
- Develop new combination treatment protocols optimized by PK/PD modeling
- Developing metronomic strategies optimized by PK/PD modeling
- Developing nanoparticles optimized by PK/PD modeling
- Develop tools to optimize combinations of immunotherapy and associated treatments.
- Develop tools for better clinical trial design, particularly in the early phases.
- Conduct pharmacokinetic analysis and biodistribution studies on small rodents
- Carry out pharmacokinetic analysis in phase I and phase I/II clinical trials in an Iso15189 environment.

PROJECTS TO WHICH THE PLATFORM CONTRIBUTES

Thermonano

PROJECT OFFICER

Julien Nicolas

Project members :

Anne Rodallec
Teacher-researcher

Patricia Piris

Sophie Marolleau
Engineer

Our partner Julien Nicolas from Paris Saclay has developed a series of polymers enabling subcutaneous administration of chemotherapies usually injected intravenously. This formulation has already demonstrated clear pharmacokinetic and pharmacodynamic advantages.

Our role in this project was twofold:

Fluorescent imaging testing of subcutaneous administration of this formulation via an innovative needle-free device.
Use pharmacokinetic/pharmacodynamic modeling to define the best administration schedule (dose, frequency) for this new formulation.

PIONEER

PROJECT OFFICER

Fabrice Barlesi

Project members :

Joseph Ciccolini
Researcher - Hospital Practitioner

Sophie Marolleau
Engineer

Mourad HAMIMED
Doctoral student

Carla Perez
Doctoral student

The rise of immune checkpoint inhibitors (ICIs) has led to significant improvements in survival rates for advanced non-small cell lung cancer (NSCLC ). However, only 20-30% of patients treated with ICIs benefit in terms of long-term survival.

Our role in this project :

Provide bioanalytical expertise with pharmacological therapeutic monitoring of nivolumab, pembrolizumab and atezolizumab.
Explore pharmacokinetic/pharmacodynamic (PK/PD) relationships in NSCLC patients.

Our results showed that residual pembrolizumab levels after the first course of treatment were an independent predictive marker of treatment response. What's more, all patients on atezolizumab were highly overexposed, suggesting that de-escalation may be possible.

MOIO

PROJECT OFFICER

Gwenaelle Gravis-Mescam

Project members :

Joseph Ciccolini
Researcher - Hospital Practitioner

Mourad HAMIMED
Doctoral student

Immune checkpoint inhibitors are currently **overdosed** in relation to the required maintenance of plasma concentrations associated with target engagement. It remains to be determined to what extent prolonged **intervals** between administrations would guarantee adequate exposure levels .

Project objectives :

Demonstrate **non-inferiority** in terms of progression-free survival (PFS) of reduced-dose RO compared with standard RO.
Evaluate this approach in patients responding after 6 months of standard IO.

Endpoint: Progression-free survival (PFS), calculated from date of randomization to date of first progression or death from any cause.

NANOIMMUNO

PROJECT OFFICER

Camille Lombard

PROJECT OFFICER

Raphaëlle Fanciullino

Project members :

Mathilde Dacos
Doctoral student

Joseph Ciccolini
Researcher - Hospital Practitioner

Sarah Giacometti
Technician

Anne Rodallec
Teacher-researcher

Immune checkpoint inhibitors are considered revolutionary innovations in oncology, but their efficacy remains limited to a small group of patients and a restricted number of tumors.

Several factors explain the failure of immunotherapy in many contexts:

Presence of an immune desert, with absence of infiltrating lymphocytes in the tumor microenvironment.
Overexpression of Tregs and MDSCs, which negatively regulate the immune response.
Limited immunogenicity of cancer cells.

Combinatorial therapy is now seen as the future of immunotherapy, as it aims to transform cold tumors into warm ones. Among the most promising approaches, nanoparticles present unique and attractive characteristics, but their combination modalities have yet to be studied.

Project objectives :

Evaluate the immunomodulatory properties of our ANC-1 nanoparticles (immunoliposome encapsulating docetaxel and labeled with anti-Her2 trastuzumab) in breast cancer models.
Determine the optimal modalities for a future combination of ANC-1, anti-VEGF (bevacizumab) and anti-PDL1 (atezolizumab) in breast cancer.