A44
Building robust pharmacodynamic biomarker assays for phase I clinical trials
Simon Heaton1, Shaun Decordova1, Samantha Costigan1, Matthew Tall1, Anthea Hardcastle1, G. Wynne Aherne1, Johann de Bono2, Udai Banerji2, Michelle D. Garrett1
1Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Sutton, UK, 2Section of Medicine, The Institute of Cancer Research, Sutton, UK
Before a molecularly targeted agent enters clinical evaluation, it is important to consider the importance of being able to effectively demonstrate drug-dependent target modulation in the patient. This is known as a pharmacodynamic (PD) biomarker response. Within the context of a phase I clinical trial, the information gained from monitoring the PD biomarker response, together with pharmacokinetic (PK) data, can help clinicians to optimise drug dosing and scheduling for further Phase I /II trials. This can only be achieved by developing fit for purpose sample processing procedures and robust PD biomarker assays.
In addition, the clinical drug profiling to determine the PK-PD relationship is being conducted to increasingly rigorous standards, demonstrated by the introduction of the European Directive 2001/20/EC, which became UK law in 2004. With this in mind, a group has been established within Cancer Therapeutics to develop PD assays to the required standard. An initial focus has been the development of assays to detect target modulation of those compounds developed within Cancer Therapeutics and initially those that target the PI3 Kinase/AKT pathway, HSP90 and HDACs. Examples of its validation work for these assays and the clinical trials that The Institute is currently involved with will be presented.
