AUTHOR=Catani Greta , Morchón-Araujo Daniel , Mirallas Oriol , Sánchez-Pérez Vicky , Nuciforo Paolo , Villacampa Guillermo , Dienstmann Rodrigo , Vivancos Ana , Garralda Elena , Hernando-Calvo Alberto 

TITLE=Optimizing early-phase immunotherapy trials: the role of biomarker enrichment strategies

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1664443

DOI=10.3389/fimmu.2025.1664443

ISSN=1664-3224

ABSTRACT=Immune checkpoint inhibitors have revolutionized the treatment of solid tumors; however, their clinical efficacy remains limited to a subset of patients. Novel immunotherapy agents are being investigated in phase I clinical trials, with an increasing focus on biomarker selection strategies to optimize patient outcomes. Prior evidence suggests that biomarker-selected tumors may have better outcomes when treated with molecularly-guided therapies. However, the high complexity of tumor-host interactions and inter-patient variability indicates that a one-size-fits-all biomarker approach is unlikely to be sufficient in the immunotherapy landscape. This review highlights current biomarker-enrichment strategies in immunotherapy early drug development, addressing challenges and potential future directions for their effective implementation.