Rethinking Phase I units in the era of immuno-oncology: a three-layer framework

Area of Science:

• Oncology
• Clinical Pharmacology
• Drug Development

Background:

• Immuno-oncology and advanced therapies increase early-phase clinical development complexity.
• Phase I unit organizational functions lag behind emerging therapeutic modalities.
• Current Phase I units primarily focus on conventional operational responsibilities.

Purpose of the Study:

• To propose a global perspective on the future development of Phase I units.
• To present a framework for evolving Phase I units to meet new therapeutic demands.
• To provide guidance for building future-ready early-phase clinical research infrastructure.

Main Methods:

• Analysis of leading Phase I units in the USA, Europe, and China.
• Comparison of evolving regulatory frameworks (FDA, EMA/MHRA, NMPA).
• Development of a three-layer framework for Phase I unit development.

Main Results:

• A three-layer framework is proposed: core foundations, advanced translational capabilities, and ecosystem-level functions.
• Modern Phase I units should integrate translational research, AI, model-informed drug development, regulatory science, and public engagement.
• Specialized centers may support advanced therapy infrastructure like point-of-care manufacturing.

Conclusions:

• Phase I units must evolve into integrated platforms connecting clinical investigation, translational science, and regulatory innovation.
• A collaborative network model can facilitate scalable implementation and international harmonization.
• This framework offers practical guidance for future-ready early-phase clinical research infrastructure worldwide.