A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy

Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new ins...

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Main Authors: Pedro J Romero, Leisha A Emens, Elizabeth Garrett-Mayer, Valsamo Anagnostou, Jason J Luke, Ann W Silk, Thomas U Marron, Jane Perlmutter, Brianna Hoffner, Connie Szczepanek
Format: Article
Language:English
Published: BMJ Publishing Group 2025-03-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/13/3/e010760.full
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author Pedro J Romero
Leisha A Emens
Elizabeth Garrett-Mayer
Valsamo Anagnostou
Jason J Luke
Ann W Silk
Thomas U Marron
Jane Perlmutter
Brianna Hoffner
Connie Szczepanek
author_facet Pedro J Romero
Leisha A Emens
Elizabeth Garrett-Mayer
Valsamo Anagnostou
Jason J Luke
Ann W Silk
Thomas U Marron
Jane Perlmutter
Brianna Hoffner
Connie Szczepanek
author_sort Pedro J Romero
collection DOAJ
description Clinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new insights into how the mechanistic underpinnings of IO are reflected in the clinic. These insights and the sheer number of novel immunotherapies currently in the pipeline have made it clear that our strategies and tools for IO drug development must adapt. Recent innovations like engineered T cells and tumor-infiltrating lymphocytes demonstrate that immune-based treatments may rely on real-time manufacturing programs rather than off-the-shelf drugs. We now recognize adoptively transferred cells as living drugs. Progression criteria have been redefined due to the unique response patterns of IO. Harnessing the power of both biomarkers and the neoadjuvant setting earlier in drug development is of broad interest. The US Food and Drug Association is increasingly impacting the design of trials with respect to dose optimization and clinical endpoints. The use of novel endpoints such as pathologic complete/major response, treatment-free survival, and minimal residual disease is becoming more common. There is growing acceptance of using patient-reported outcomes as trial endpoints to better measure the true clinical benefit and impact of novel IO agents on quality of life. New opportunities created by modern data science and artificial intelligence to inform and accelerate drug development continue to emerge. The importance of streamlining the clinical research ecosystem and enhancing clinical trial access to facilitate the enrollment of diverse patient populations is broadly recognized. Patient advocacy is critical both to drive the science of IO, and to promote patient satisfaction. To capitalize on these opportunities, the Society for Immunotherapy of Cancer (SITC) has established a goal of at least 100 new, unique IO approvals over the next 10 years. Accordingly, SITC has developed initiatives designed to integrate the viewpoints of diverse stakeholders and galvanize the field in further adapting clinical trials to the unique features of IO, moving us closer to our ultimate goal of using IO to cure and prevent cancer.
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spelling doaj-art-a5c601d2ea914753a2591bf265ccb24f2025-08-20T02:32:38ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-03-0113310.1136/jitc-2024-010760A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapyPedro J Romero0Leisha A Emens1Elizabeth Garrett-Mayer2Valsamo Anagnostou3Jason J Luke4Ann W Silk5Thomas U Marron6Jane Perlmutter7Brianna Hoffner8Connie Szczepanek98 Novigenix SA, Epalinges, Switzerland10 Kaiser Permanente, South Sacramento, California, USA9 Center for Research and Analytics, American Society of Clinical Oncology, Alexandria, Virginia, USA6 Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA2 UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA7 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA1 Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA4 Gemini Group, Ann Arbor, Michigan, USA3 Advanced Practitioner Society for Hematology and Oncology, Hightstown, New Jersey, USA5 Cancer Research Consortium of West Michigan (CRCWM), Grand Rapids, Michigan, USAClinical trials of cancer immunotherapy (IO) were historically based on a drug development paradigm built for chemotherapies. The remarkable clinical activity of programmed cell death protein 1/programmed death ligand 1 blockade, chimeric antigen receptor-T cells, and T cell engagers yielded new insights into how the mechanistic underpinnings of IO are reflected in the clinic. These insights and the sheer number of novel immunotherapies currently in the pipeline have made it clear that our strategies and tools for IO drug development must adapt. Recent innovations like engineered T cells and tumor-infiltrating lymphocytes demonstrate that immune-based treatments may rely on real-time manufacturing programs rather than off-the-shelf drugs. We now recognize adoptively transferred cells as living drugs. Progression criteria have been redefined due to the unique response patterns of IO. Harnessing the power of both biomarkers and the neoadjuvant setting earlier in drug development is of broad interest. The US Food and Drug Association is increasingly impacting the design of trials with respect to dose optimization and clinical endpoints. The use of novel endpoints such as pathologic complete/major response, treatment-free survival, and minimal residual disease is becoming more common. There is growing acceptance of using patient-reported outcomes as trial endpoints to better measure the true clinical benefit and impact of novel IO agents on quality of life. New opportunities created by modern data science and artificial intelligence to inform and accelerate drug development continue to emerge. The importance of streamlining the clinical research ecosystem and enhancing clinical trial access to facilitate the enrollment of diverse patient populations is broadly recognized. Patient advocacy is critical both to drive the science of IO, and to promote patient satisfaction. To capitalize on these opportunities, the Society for Immunotherapy of Cancer (SITC) has established a goal of at least 100 new, unique IO approvals over the next 10 years. Accordingly, SITC has developed initiatives designed to integrate the viewpoints of diverse stakeholders and galvanize the field in further adapting clinical trials to the unique features of IO, moving us closer to our ultimate goal of using IO to cure and prevent cancer.https://jitc.bmj.com/content/13/3/e010760.full
spellingShingle Pedro J Romero
Leisha A Emens
Elizabeth Garrett-Mayer
Valsamo Anagnostou
Jason J Luke
Ann W Silk
Thomas U Marron
Jane Perlmutter
Brianna Hoffner
Connie Szczepanek
A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
Journal for ImmunoTherapy of Cancer
title A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
title_full A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
title_fullStr A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
title_full_unstemmed A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
title_short A SITC vision: adapting clinical trials to accelerate drug development in cancer immunotherapy
title_sort sitc vision adapting clinical trials to accelerate drug development in cancer immunotherapy
url https://jitc.bmj.com/content/13/3/e010760.full
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