Abstract ES5-3: Development of molecular and genomic biomarkers: A regulatory path forward
Authors: Beaver JA 
Published: May 2016

Abstract
Due to advancements in tumor genomics, and a better understanding of the molecular subtypes and heterogeneity of breast cancer, there is great interest in molecular and genomic biomarker development.
There are many ways in which molecular and genomic biomarkers can be incorporated into breast cancer clinical trials. Diagnostic biomarkers can be utilized to identify a more homogeneous cancer population to study. Prognostic or predictive biomarkers can be useful for trial stratification and enrichment. Biomarkers of tumor response could be incorporated into clinical trials leading to earlier evaluations of antitumor activity. There is also the potential for a response biomarker to be studied as a potential surrogate endpoint or efficacy-response biomarker that is intended to substitute for a clinical endpoint expected to predict long-term outcome.
Biomarkers can become accepted by the US Food and Drug Administration for use in therapeutic product (either a novel product or an existing product with a new indication) development via two potentially complementary regulatory pathways. The first is in the context of a specific therapeutic product within an investigational new drug application and ultimately included in a drug label after approval of both a therapeutic product and a companion diagnostic device. This pathway requires close collaboration between Center for Drug Evaluation and Research (CDER) and Center for Devices and Radiological Health (CDRH). During drug development, CDRH will assess the investigational biomarker test and determine the level of risk that the device may present to the health and safety of patients; CDER will provide guidance on the clinical trial design and the biomarker development plan in the context of the product. At the time of the NDA or BLA submission, if the biomarker test is deemed essential for the safe and effective use of the therapeutic product, then the companion diagnostic is expected to be approved or cleared contemporaneously with the corresponding therapeutic product. The companion diagnostic is reviewed by CDRH to determine if there is valid scientific evidence to provide reasonable assurance that the device is safe and effective for its intended use. CDER will perform the appropriate NDA or BLA review with consideration of the biomarker. If appropriate, the biomarker would then become accepted in the context of the therapeutic product and disease setting and be incorporated in the label. The second pathway is through the FDA biomarker qualification program where a pharmaceutical developer, health research group, patient foundation, or consortium may request regulatory “qualification” of a biomarker. A multidisciplinary team is formed, advice is given, and if qualified, a biomarker can be relied upon to have a specific interpretation and application in drug development and regulatory review within the stated context of use for clinical trials across different therapeutic products.
Biomarkers should continue to be a priority through drug development and communication with FDA is critical to successful incorporation of biomarkers into clinical trials. Biomarkers used correctly in clinical trials have the potential to advance the development of highly effective treatments for breast cancer patients.
Citation Format: Beaver JA. Development of molecular and genomic biomarkers: A regulatory path forward. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr ES5-3.