Project Optimus and dose optimization in oncology
Project Optimus is an initiative of the US FDA Oncology Center of Excellence to improve dose selection in oncology drug development, moving beyond the maximum tolerated dose to doses with the best benefit–risk, supported by randomized dose comparisons.
Definition
Project Optimus is an initiative of the Oncology Center of Excellence of the US Food and Drug Administration. It aims to improve how doses are selected in oncology drug development. Historically the dose was often the maximum tolerated dose from early cytotoxic-drug trials; for targeted therapies and antibody drugs the dose with the best balance of benefit and risk may be lower.
What it asks for
Sponsors are encouraged to compare more than one dose, with randomized dose-finding where appropriate, using exposure, efficacy, safety and tolerability together (exposure–response analysis) before settling on the dose to take forward.
On this site
The sotorasib analysis uses the arm-level data of a randomized 960 mg versus 240 mg comparison and shows how the choice depends on the weight given to benefit and harm. The ifinatamab deruxtecan analysis asks whether another dose comparison would be informative, and the borrowing analysis asks how much of an existing drug's dose comparison a new drug can borrow. None of them recommends a dose.
Frequently asked questions
Why is the maximum tolerated dose not always the right dose?
For targeted therapies and antibodies, higher doses may add toxicity without more benefit, so the dose with the best benefit–risk can be lower.
Does this site say which dose is right?
No. The analyses use public data to show what a dose comparison can and cannot support, and none recommends a dose.