Biomarker-driven patient selection for early clinical trials

Abstract

In this study we describe a new trend in biomarker-driven early drug development using enrichment and prescreening strategies. Technical and logistical obstacles that may hinder progress of this approach will be discussed, along with the ethical and financial concerns. Advances in tumor biology and human genetics with the identification of driver events and critical dependencies together with the development of drugs for specific targets hold promise for an era of personalized oncology treatment. Phase I trials provide an arena for early hypothesis testing, examining not only safety and toxicity, but also target engagement, biologically effective dosages, and the appropriate patient population. Integrating biomarker development into the early testing of novel agents might provide clinically relevant therapeutic opportunities for patients with advanced-stage cancer and also accelerate the drug approval process. After recent success stories with therapies targeting driver molecular aberrations in genetically defined tumor subtypes, innovative trials based on strong biological hypotheses are expected to bring further excitement to the field. Tumor heterogeneity and clonal evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will have to be taken into consideration in the scenario of drug development.