Precision Medicine: The Function of Receptor Occupancy Assays in Drug Development
Sponsored by: Covance
Date: 26 June
Time: 4PM London/11AM New York
Along with phenotyping and functional testing used for immune monitoring, receptor occupancy (RO) assays have become a standard application in flow cytometry in the context of drug development, particularly in indications where biologics are the therapeutic modality.
In Phase I studies, RO assays can play an important role in dose selection and can confirm target occupancy observed in animal models. During Phase II and III clinical trials, RO assays enable Pharmacokinetic (PK)/Pharmacodynamic (PD) modeling and help guide the dose of administered drug. For example, anti-PD1, anti-PD-L1, AMG479, ATR107, Etrolizumab or VX15/2503 are among the therapeutic antibodies for which RO information on circulating cells have been used as PD biomarker.
However, there are multiple technical and logistical challenges associated with the development, optimization, validation and implementation of RO assays for multi-center clinical trials. In addition, like any other flow assays used for multi-center studies, the quality and longitudinal comparability of the generated data largely relies on optimum assay development and validation inclusive of selection and robust quality control/titration of detection reagents, target prevalence and stability, inter-instrument standardization process, global standard operating procedures (SOPs) and appropriate staff training.
In this presentation, we will discuss different technical approaches that can be used to assess RO by flow cytometry and explore the various pros and cons of each approach. Finally, we review the challenges that can be encountered during RO assay development, validation and implementation for multi-center clinical trials.
Leanne Flye-Blakemore, M.S.,
Senior Manager, Assay Development and Validations
Leanne Flye-Blakemore is an experienced cytometrist specializing in cell signal transduction, RO, and apoptosis assay development and validations specific to the areas of oncology, autoimmune disorders and infectious disease. Her specific experiences range from detection of activation and inhibition of cellular pathways in autoimmune illnesses, solid tumor surrogates and heme-malignancies to receptor occupancy assays in those same indications. She is skilled in reagent formulation, GMP guidelines and all phases of clinical trials from assay development and validation, assay implementation within central labs, and consultation for operational oversight. She received her Master's in Science with a concentration in cell signal transduction in 2005 and has been actively working in flow cytometry since 2001. Leanne holds two patents in her field and has been employed by Covance/LabCorp for 19 years.
Key Learning Objectives
- Proper clone section and receptor occupancy approach
- Proper background determination (how not to have apparent occupancy at pre-dose)
- Standardization for quantitative receptor occupancy
- Challenges with receptor occupancy
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