Incorporating precision medicine into phase I clinical trials

There has been growing interest in molecular profiling of tumors in order to identify actionable alterations and offer molecularly matched therapies. Given the rapid incorporation of next generation sequencing into clinical care, genomic profiling has led the way with transcriptional profiling and immune profiling closely following. Increasing numbers of Phase I trials are biomarker-selected, and there are large number of biomarker-selected Phase II basket trials or signal-seeking expansions. Although there have been several recent successes, genomically-informed therapy has several challenges. In this chapter we will review the pros and cons of biomarker-selected early phase therapies and review strategies for patient screening. We will also review challenges in genomically-informed therapy including need for functional annotation and determining decision support, tumor heterogeneity, genomic evolution, and management of incidental results.