Precision Cancer Trials With Immunomodulatory Agents

Abstract Advances in high-throughput technologies have yielded impressive insights into the molecular biology behind cancers, resulting in a powerful ally for the development of biomarkers-selected clinical trials, which are critical for translating our genomic knowledge into clinically meaningful outcomes. “Basket studies” or histology-agnostic clinical trials in biomarker-defined populations represent an important research strategy to continue making progress in this field. The recent accelerated US Food and Drug Administration approvals of anti–programmed death 1 pembrolizumab and nivolumab for mismatch repair–deficient cancers, as well as larotrectinib for cancers carrying TRK fusions, support the fundamental premise that some cancers may be best classified based on molecular phenotype and not site of origin. The studies that were conducted showing the efficacy of this approach serve as validation of the basket study paradigm. In the field of immune oncology, the advent of tumor agnostic strategies represents an important step toward discovering biomarkers of response and elucidating mechanisms of treatment efficacy and resistance across a variety of cancer types. We present a review and discussion of the progress in biomarker-defined approaches to drug development in immunology.