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First-in-Human Phase 1 Studies in Oncology: The New Challenge for Investigative Sites
1Medpace Inc., Cincinnati, OH, USA and Università degli Studi, Milan, Italy.
Abstract:
Phase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies. Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.
Insights
Phase 1 cancer drug studies require new designs for targeted therapies evaluated in patients, not healthy volunteers. This ensures effective development of novel anti-cancer compounds.
Area of Science:
- Oncology
- Clinical Pharmacology
- Drug Development
Background:
- Phase 1 studies for anti-cancer products are unique, involving patients instead of healthy volunteers.
- Targeted drug development necessitates precise patient population definitions, posing challenges for efficient trial enrollment.
Purpose of the Study:
- To outline the evolving design considerations for Phase 1 first-in-human studies of novel targeted anti-cancer agents.
- To address the challenges and necessary adaptations in conducting early-phase oncology clinical trials.
Main Methods:
- The abstract discusses shifts in objectives from maximum tolerated dose to recommended Phase 2 dose.
- It highlights the need for biological dose definitions and fresh tumor tissue collection for biomarker analysis.
- Management of infusion-related reactions for monoclonal antibodies is also considered.
Main Results:
- Phase 1 oncology trials require modifications in design and conduct compared to traditional Phase 1 studies.
- Novel targeted therapies necessitate specific approaches, including defining biological doses and managing unique toxicities.
- Adaptations are crucial for evaluating efficacy and safety profiles of new anti-cancer drugs.
Conclusions:
- Conducting Phase 1 clinical trials in oncology demands significant changes in study design and execution.
- Integrated education on Phase 1 trials and drug development is essential for medical and nursing staff.
- Institutions must adapt to remain competitive in early-phase clinical research for novel anti-cancer compounds.
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