Abstract
The exploratory phase of oncology drug development starts with the establishment of a dose and schedule that achieves the desired plasma exposure and target engagement while maintaining an acceptable safety profile and ends with a drug that is positioned for a registrational trial. The progression of a drug candidate through exploratory phase of development requires a robust, mechanistic hypothesis about how the drug interacts with the target to achieve anti-tumor activity. This therapeutic hypothesis informs the design and interpretation of dose-finding safety studies and studies designed to identify anti-tumor activity. Dose-finding studies should have pre-specified pharmacokinetic and pharmacodynamic objectives that define the desired dose and schedule for subsequent development. Studies to establish preliminary efficacy should also be hypothesis driven to provide evidence of target-dependent clinical activity at the correct dose and schedule. A hypothesis-driven approach to this initial stage of drug development can improve the likelihood of success in adult Phase 3 trials as well as facilitating evaluation of the drug candidate in pediatric cancers.
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DiMartino, J. (2022). Exploratory Clinical Development: From First in Humans to Phase 3 Ready. In: DiMartino, J., Reaman, G.H., Smith, F.O. (eds) Pediatric Cancer Therapeutics Development. Pediatric Oncology. Springer, Cham. https://doi.org/10.1007/978-3-031-06357-2_5
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