Oncology Combination Drug Development Strategies for Project Optimus

Abstract The Project Optimus initiative from the FDA introduced a new dose optimization and selection paradigm in oncology drug development. The FDA has outlined approaches to dose optimization for single agents, but multiple oncology drugs are being developed for use in combination with other therapies. Dose optimization in the context of combination drug development is complex and requires a case-by-case approach. It necessitates commitment to the totality of available evidence, leveraging all relevant data on mechanism of action, nonclinical and clinical pharmacology, safety, and principles of model-informed drug development. In this article, we outline key considerations for sponsors and investigators pursuing dose optimization with combinatorial regimens. We illustrate important strategies for dose optimization in the combination setting using a range of hypothetical case examples that represent typical drug development scenarios. Close discussions and collaboration with regulators regarding the optimal approaches to these scenarios will continue to be critical.