Dose Optimization: A Strategic Lever In Oncology Drug Development

The future of oncology drug development hinges on a pivotal question: Are we dosing patients in a way that truly helps them thrive? For decades, the field leaned heavily on the maximum tolerated dose (MTD) as the default path forward — a model built for cytotoxic therapies where “more drug” often meant “more effect.” But today’s oncology landscape looks entirely different. Targeted therapies, immunotherapies, antibody–drug conjugates, and other complex biologics demand a more nuanced, patient-centered strategy, and one that recognizes that higher doses do not always translate to better outcomes.

This shift is the foundation of Project Optimus, the FDA’s initiative designed to redefine regulatory expectations for dose selection in oncology. Under this framework, dose optimization is no longer a peripheral exercise; it is a core component of clinical strategy. Sponsors are expected to move beyond identifying the highest dose patients can tolerate and instead determine the dose that best balances efficacy, safety, and tolerability. The FDA has made the stakes clear: inadequate dose characterization can lead to greater toxicity without additional efficacy, driving unnecessary dose reductions, treatment discontinuations, and missed opportunities for durable benefit.

In response, many oncology sponsors are prioritizing dose optimization from the earliest phases of development. Using integrated pharmacokinetic and pharmacodynamic assessments, exposure–response modeling, biomarkers, and patient-reported outcomes, teams must now justify their dose selection with scientific rigor. The goal is to identify the Optimal Biological Dose (OBD): the dose that maximizes therapeutic effect while maintaining an acceptable safety profile.

This regulatory evolution signals a broader truth: thoughtful dose optimization is not just a requirement under Project Optimus — it is a competitive advantage and a clearer path to delivering therapies that patients can tolerate, remain on, and ultimately benefit from.