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REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1664443

This article is part of the Research TopicEarly Phase Clinical Trials for the Development of Novel Immunotherapeutic Anti-Cancer AgentsView all 6 articles

Optimizing Early-Phase Immunotherapy Trials: The role of biomarker enrichment strategies

Provisionally accepted
Greta CataniGreta Catani1,2Daniel Morchón-AraujoDaniel Morchón-Araujo2,3Oriol MirallasOriol Mirallas2,4,5Vicky Sánchez-PérezVicky Sánchez-Pérez2,4Paolo NuciforoPaolo Nuciforo2Guillermo VillacampaGuillermo Villacampa2Rodrigo DienstmannRodrigo Dienstmann6,7,8Ana VivancosAna Vivancos2Elena GarraldaElena Garralda2,4Alberto Hernando-CalvoAlberto Hernando-Calvo2,4*
  • 1Alexander Fleming Specialized Medical Institute, Buenos Aires, Argentina
  • 2Vall d'Hebron Institut d'Oncologia, Barcelona, Spain
  • 3Department of Medical Oncology, Hospital Universitario de Salamanca, Salamanca, Spain
  • 4Department of Medical Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain
  • 5Departament de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain
  • 6Oncology Data Science, Vall d'Hebron Institut d'Oncologia, Barcelona, Spain
  • 7Universitat de Vic - Universitat Central de Catalunya, Vic, Spain
  • 8OC Medicina de Precisão, Oncoclínicas & Co, Sao Paulo, Brazil

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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.

Keywords: biomarker, immune checkpoint inhibitors, early-phase trials, phase 1, Immunotherapy, Drug response biomarkers, predictive biomarkers

Received: 11 Jul 2025; Accepted: 30 Sep 2025.

Copyright: © 2025 Catani, Morchón-Araujo, Mirallas, Sánchez-Pérez, Nuciforo, Villacampa, Dienstmann, Vivancos, Garralda and Hernando-Calvo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Alberto Hernando-Calvo, albertohernando@vhio.net

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material