A5077835854- Mathematical Biology Tumor Growth
- Cancer Treatment and Pharmacology
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Protein Degradation and Inhibitors
- Lung Cancer Research Studies
- Pharmacogenetics and Drug Metabolism
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Neutropenia and Cancer Infections
- Gene Regulatory Network Analysis
- Statistical Methods in Clinical Trials
- Advanced Biosensing Techniques and Applications
- Neuroblastoma Research and Treatments
- Computational Drug Discovery Methods
- Cell death mechanisms and regulation
- Molecular Communication and Nanonetworks
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic and Hepatic Oncology Research
- bioluminescence and chemiluminescence research
Roche (Switzerland)
2014-2023
Novartis (Switzerland)
2016-2022
Novartis Institutes for BioMedical Research
2017-2021
Inserm
2016-2017
Aix-Marseille Université
2006-2017
Centre de Recherche en Cancérologie de Marseille
2016
Institut de Neurobiologie de la Méditerranée
2008
Hospices Civils de Lyon
2007
Université Claude Bernard Lyon 1
2005-2007
Centre Georges François Leclerc
2007
Asciminib is an allosteric inhibitor that binds a myristoyl site of the BCR-ABL1 protein, locking into inactive conformation through mechanism distinct from those for all other ABL kinase inhibitors. targets both native and mutated BCR-ABL1, including gatekeeper T315I mutant. The safety antileukemic activity asciminib in patients with Philadelphia chromosome-positive leukemia are unknown.
Combining radiotherapy with immune checkpoint blockade may offer considerable therapeutic impact if the immunosuppressive nature of tumor microenvironment (TME) can be relieved. In this study, we used mathematical models, which illustrate potential synergism between inhibitors and radiotherapy. A discrete-time pharmacodynamic model combination PD1-PDL1 axis and/or CTLA4 pathway is described. This framework describes how a growing first elicits then inhibits an antitumor response. response...
Early prediction of human clearance is often challenging, in particular for the growing number low-clearance compounds. Long-term vitro models have been developed which enable sophisticated hepatic drug disposition studies and improved predictions. Here, cell line HepG2, iPSC-derived hepatocytes (iCell®), stem HepaRG™, hepatocyte co-cultures (HμREL™ HepatoPac®) were compared to primary suspension cultures with respect their key metabolic activities. Similar activities found long-term HμREL™,...
Abstract Purpose: This phase I, dose-escalation study investigated the recommended dose for expansion (RDE) of siremadlin, a p53–MDM2 inhibitor, in patients with wild-type TP53 advanced solid or hematologic cancers. Patients and Methods: Initial dosing regimens were: 1A (day 1; 21-day cycle; 12.5–350 mg) 2A (days 1–14; 28-day 1–20 mg). Alternative included 1B 1 8; cycle) 2C 1–7; cycle). The primary endpoint was incidence dose-limiting toxicities (DLT) during cycle 1. Results: Overall, 115...
Antitumor clinical activity has been demonstrated for the MDM2 antagonist RG7112, but patient tolerability necessary daily dosing was poor. Here, utilizing RG7388, a second-generation nutlin with superior selectivity and potency, we determine feasibility of intermittent to guide selection initial phase I scheduling regimens.A pharmacokinetic-pharmacodynamic (PKPD) model developed on basis preclinical data alternative schedule requirements optimal RG7388-induced antitumor activity. This PKPD...
Metronomic chemotherapy is usually associated with better tolerance than conventional chemotherapy, and encouraging response rates have been reported in various settings. However, clinical development of metronomic has hampered by a number limitations, including the vagueness its definition resulting empiricism protocol design. In this study, we developed pharmacokinetic/pharmacodynamic mathematical model that identifies silico most effective administration schedule for gemcitabine...
Abstract Background CGM097 inhibits the p53-HDM2 interaction leading to downstream p53 activation. Preclinical in vivo studies support clinical exploration while providing preliminary evidence for dosing regimens. This first-in-human phase I study aimed at assessing safety, MTD, PK/PD and antitumor activity of advanced solid tumour patients (NCT01760525). Methods Fifty-one received oral treatment with 10–400 mg 3qw ( n = 31) or 300–700 2 weeks on/1 week off 20). Choice dose regimen was...
Metronomic oral vinorelbine is effective in metastatic NSCLC and malignant pleural mesothelioma, but all the studies published thus far were based upon a variety of empirical possibly suboptimal schedules, with inconsistent results. Mathematical modelling showed by simulation that new metronomic protocol could lead to better safety efficacy profile. This phase Ia/Ib trial was designed confirm (phase Ia) evaluate Ib) schedule. Patients or mesothelioma whom standard treatments failed who...
RG7116 is a novel anti-HER3 therapeutic antibody that inhibits HER3 signalling and induces antibody-dependent cellular cytotoxicity of tumor cells due to glycoengineered Fc moiety. We investigated the efficacy pharmacokinetic/pharmacodynamic properties signal inhibition by in murine xenograft model human head neck cancer.SCID-beige mice bearing FaDu were treated with at weekly dose 0.3-10 mg/kg, growth control modulation selected proteins (HER3 AKT) examined.Complete stasis up Day 46 was...
Optimizing new drug therapies remains a challenge for clinical development, despite the use of ever more sophisticated quantitative methodologies. Although conceptually simple, idea finding right treatment at dose patient to ensure an appropriate balance risks and benefits is challenging requires multidisciplinary approach. In this paper, we present framework developed as tool organizing knowledge facilitating collaboration in development teams.
Assessment of the maximum tolerated dose for a small sample patients is objective phase I trials in oncology. We propose new adaptive approach performing differentiation each type toxicity and their grades, definition dose-limiting as logical combination events, modeling risk toxic events function drug dose, integration individual covariates. An application study with retrospective data from Taxol pediatric trial revealed age an influential covariate, allowing individualization patient's...
Radioiodine therapy (RAI) has traditionally been used as treatment for metastatic thyroid cancer, based on its ability to concentrate iodine. Propositions maximize tumor response with minimizing toxicity, must recognize the infinite possibilities of empirical tests. Therefore, an approach this study was build a mathematical model describing growth kinetics thyroglobulin (Tg) concentrations over time, following RAI cancer.Data from 50 patients papillary carcinoma treated within eight French...
Abstract Background: Well-differentiated/dedifferentiated liposarcoma (WDLPS/DDLPS) is characterized by a consistent coamplification of human double minute 2 homolog (HDM2) and cyclin-dependent kinase 4 (CDK4) which inactivates the tumor suppressor pathways p53 Rb, respectively. HDM201 selective inhibitor p53-HDM2 interaction ribociclib CDK4/6 inhibitor. Preclinical studies suggested synergy in vitro vivo models WDLPS/DDLPS both agents have demonstrated single-agent clinical activity solid...
Abstract Background: NVP-HDM201 is a selective inhibitor of the p53-HDM2 interaction and has demonstrated potent single-agent activity in various vitro vivo tumor models, dependent on wild-type (wt) TP53. This study aims to determine optimal dose schedule for treating patients (pts) with TP53 wt tumors further clinical study. Here we focus pts advanced, acute leukemias. Methods: In this multicenter, open-label, dose-finding, Phase I study, who had relapsed or refractory myeloid leukemia...