Fit-for-Purpose Gene Expression-based Clinical Biomarkers in Oncology and Immuno-Oncology: Why and How?
Shashwati Basak,
Lead Investigator & Head-Clinical Genomics,
BBRC, Syngene International Limited
Cancer biomarkers play an important role during all phases of drug discovery and development
and in guiding early clinical decision. Amongst the various gene expression-based technologies
that are available, real-time quantitative polymerase chain reaction (RT-qPCR) technology has
become the method of choice for clinical biomarker detection and quantification for its accuracy, sensitivity, speed and cost compared to other available technologies. While a rigorous biomarker assay validation is generally not required during the initial lead identification and optimization, increasingly stringent validation becomes important as a drug progresses into preclinical and early-phase clinical studies. A “fit-for purpose” assay development and validation to meet the clinical requirements plays a significant role in biomarker quantification. Development and use of RT-qPCR technology as a robust, accurate and reproducible method is required for biomarker assay qualification during early clinical phases. Key factors influencing assay performance such as sample matrix, sample preparation, experimental precision, reproducibility, sensitivity, specificity, dilution linearity and dynamic range and their impact on the assay outcome will be discussed. Based on these, recommendations for consideration and optimization of a qPCR-based biomarker assay will be put forth. Lastly, representative examples of safety/efficacy and pharmacodynamic biomarkers that have contributed to early decision making in Oncology and Immuno-oncology clinical trials will be demonstrated.
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