{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:38:50Z","timestamp":1786451930175,"version":"build-2736575974"},"reference-count":5,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"unspecified","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272951"],"award-info":[{"award-number":["82272951"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272953"],"award-info":[{"award-number":["82272953"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC2508500"],"award-info":[{"award-number":["2023YFC2508500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Project for Medical and Health Sciences and Technology of Chinese Academy of Medical Sciences","award":["2024-I2M-TS-005"],"award-info":[{"award-number":["2024-I2M-TS-005"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,7,28]]},"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>The rapid expansion of immuno-oncology (I-O) and other advanced therapies is reshaping the complexity of early-phase clinical development. While core Phase I principles remain fundamental across oncology, emerging modalities introduce additional requirements for translational integration, specialized safety management, and therapeutic-specific infrastructure. However, the organizational functions of Phase I units have not evolved at the same pace and remain largely centered on conventional operational responsibilities. Drawing on the practices of leading Phase I units across the USA, Europe, and China, and comparing evolving regulatory frameworks of the US Food and Drug Administration, European Medicines Agency\/Medicines and Healthcare products Regulatory Agency, and China\u2019s National Medical Products Administration, we propose a global perspective on the future development of Phase I units. We present a three-layer framework encompassing core Phase I foundations applicable across oncology, advanced translational capabilities, and ecosystem-level functions supporting emerging therapeutic development. Beyond ensuring patient safety and high-quality trial conduct, modern Phase I units should integrate translational research, artificial intelligence-enabled and model-informed drug development, regulatory science, and public engagement, while specialized centers may additionally support advanced therapy infrastructure, such as point-of-care manufacturing. Recognizing the diversity of institutional resources, we further propose a collaborative network model to facilitate scalable implementation and international harmonization. This framework positions Phase I units as integrated platforms connecting clinical investigation, translational science, regulatory innovation, and emerging therapy development, providing practical guidance for building future-ready early-phase clinical research infrastructure worldwide.<\/jats:p>","DOI":"10.1136\/jitc-2026-015615","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:10:27Z","timestamp":1786450227000},"page":"e015615","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Rethinking Phase I units in the era of immuno-oncology: a three-layer framework"],"prefix":"10.1136","volume":"14","author":[{"given":"Liangjie","family":"Sun","sequence":"first","affiliation":[{"name":"Clinical Trial Center, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"},{"name":"Beijing Key Laboratory of Oncology Innovative Medicine Regulatory Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongyang","family":"Xu","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"},{"name":"Beijing Key Laboratory of Oncology Innovative Medicine Regulatory Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"},{"name":"Beijing Key Laboratory of Oncology Innovative Medicine Regulatory Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3945-2536","authenticated-orcid":false,"given":"Ning","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Trial Center, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"},{"name":"Beijing Key Laboratory of Oncology Innovative Medicine Regulatory Science, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"2026081105101938000_14.8.e015615.1","doi-asserted-by":"crossref","DOI":"10.1038\/s41746-024-01188-4","article-title":"From virtual patients to digital twins in immuno-oncology: lessons learned from mechanistic quantitative systems pharmacology modeling","volume":"7","author":"Wang","year":"2024","journal-title":"NPJ Digit Med"},{"key":"2026081105101938000_14.8.e015615.2","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2025-012331","article-title":"Mechanistic data-informed multiscale quantitative systems pharmacology modeling framework enables the clinical translation and efficacy assessment of CAR-T therapy in solid tumors","volume":"13","author":"Yang","year":"2025","journal-title":"J Immunother Cancer"},{"key":"2026081105101938000_14.8.e015615.3","unstructured":"U.S. Food and Drug Administration . 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Available: https:\/\/www.gov.uk\/government\/publications\/human-medicines-modular-manufacture-and-point-of-care-regulations-2025-overview [Accessed 10 Jun 2025]."}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2026-015615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T12:10:30Z","timestamp":1786450230000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2026-015615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":5,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,11]]},"published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1136\/jitc-2026-015615"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2026-015615","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]}}}