Guidelines for the Development and Incorporation of Biomarker Studies in Early Clinical Trials of Novel Agents

Abstract

The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and Drug Administration (FDA) guidance documents, and conducted a survey of investigators to determine practices and challenges to executing biomarker studies in clinical trials of new drugs in early development. This document provides standard definitions and categories of biomarkers, and lists recommendations to sponsors and investigators for biomarker incorporation into such trials. Our recommendations for sponsors focus on the identification and prioritization of biomarkers and assays, the coordination of activities for the development and use of assays, and for operational activities. We also provide recommendations for investigators developing clinical trials with biomarker studies for scientific rationale, assay criteria, trial design, and analysis. The incorporation of biomarker studies into early drug trials is complex. Thus the decision to proceed with studies of biomarkers should be based on balancing the strength of science, assay robustness, feasibility, and resources with the burden of proper sample collection on the patient and potential impact of the results on drug development. The Task Force provides these guidelines in the hopes that improvements in biomarker studies will enhance the efficiency of investigational drug development. Clin Cancer Res; 16(6); 1745-55. ©2010 AACR.

Methodical and pre-analytical characteristics of a multiplex cancer biomarker immunoassay

“…However, in order to be used in studies and for clinical measurements, this panel must fulfill certain requirements, such as high reliability, accuracy, robustness as well as high analytical and clinical sensitivity and specificity [18,19] . Furthermore, the analytes must be stable against potentially influencing pre-analytical factors [3] .…”

ATM serine-1981 phosphorylation is a plausible biomarker

“…1 There is an unmet need for (1) biomarkers of radiation exposure following the accidental or malicious release of radioactive material, (2) predictive biomarkers of radiation toxicity in patients treated in the oncology clinic, and (3) pharmacodynamic biomarkers for DNA damaging chemotherapy and inhibitors of DNA damage signaling kinases. 2 We recently described a facile and robust assay for ATM serine-1981 phosphorylation (ATM 1981S-P). 3 Here, we consider whether ATM 1981S-P is a plausible biomarker for these unmet needs.…”

First-in-human Phase 1 Studies in Oncology: The New Challenge for Investigative Sites

“…Every effort should be made to obtain such material, if its analysis can provide useful information concerning the definition of patient populations suitable for treatment with the investigational product and for the evaluation of the RP2D in the absence of an MTD. 6 This trend towards personalized medicine in which tumor tissue from each patient is precisely defined might reduce the importance of the histology. The future testing of a combination of targeted molecules as opposed to classical cytotoxic agents creates a paradigm shift in the definition of the phase 1 patient population in oncology.…”