What is FDA’s Project Optimus?

The FDA’s Project Optimus is a key step toward improving dose optimisation in oncology. Originally announced in 2021, the guidance aims to move away from traditional dose escalation and maximum tolerated dose (MTD) designs toward approaches that identify the dose that best balances efficacy, safety and tolerability.1 The traditional approach was developed largely around cytotoxic chemotherapy, where increasing the dose often meant increasing both efficacy and toxicity. The dose was therefore increased until safety became a concern, with the MTD then carried forward into later development. This approach is no longer appropriate for many modern oncology treatments. Higher exposure does not necessarily mean greater efficacy, being able to tolerate a treatment for longer may be more important than a slight boost to efficacy. Therefore, a dose selected at the limit of efficacy and tolerability may expose patients to additional toxicity without providing meaningful additional benefit.1,2 Ultimately, the goal is for patients to benefit from treatment doses that maintain strong efficacy while avoiding toxicity that is disproportionate or unacceptable, rather than simply pushing the limit of tolerability