Initially drafted in January 2023 and finalized in August 2024, the US Food and Drug Administration (FDA) released guidance tied to Project Optimus, titled “Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Diseases.” The Project Optimus initiative recommends oncology drug developers move away from traditional approaches of determining the maximum tolerated dose to building dose optimization strategies into clinical development plans that balance safety, tolerability, and efficacy. Since the release of the guidance, early-phase oncology drug development has shifted dramatically, including new dose escalation designs (a 3+3 is no more), larger sample sizes, real-time PK/PD sampling, randomization between doses, and global reach for patient access. Session panelists will discuss these new guidance's and how they have lead to larger sample sizes, larger global footprints, and higher study costs as well as the aim of Project Optimus to ensure a more robust safety and efficacy profile early in the development cycle. Attendees will learn how this can result in streamlined later-phase studies and more success.