OnCo
termsTerm

Project Optimus

An FDA programme pushing companies to find the best dose of a cancer drug, not just the highest tolerable one.

Launched by the FDA Oncology Center of Excellence in 2021, Project Optimus requires randomised dose comparison and exposure-response work before pivotal trials, reversing the maximum-tolerated-dose paradigm inherited from chemotherapy. It has changed early-phase design for targeted agents and ADCs (dose-optimisation cohorts, lower approved doses such as sotorasib 240 mg).

Regulatory: what this kind of term is about · animated schematic, not to scale
Category
Regulatory

Key papers

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reviewNew England Journal of Medicine 2021changed practice
FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high

The dose on the label is often not the best dose for patients; it is the highest one that was tolerable for a few weeks. Project Optimus means new cancer drugs should arrive with evidence on dose, and it gives clinicians licence to consider dose reduction for toxicity. For older drugs, the evidence gap persists.

Connected

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technologies

2
Antibody-drug conjugate (ADC)Small-molecule kinase inhibitors

drugs

1
ApprovedSmall-molecule inhibitor (KRAS G12C)
Sotorasib · Lumakras

terms

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Dose reduction, interruption and discontinuationDose-escalation designs (3+3, BOIN, dose-expansion)Dose-limiting toxicity (DLT)Maximum tolerated dose (MTD)Pharmacokinetics (PK), half-life and exposureRecommended phase 2 dose (RP2D)Therapeutic index (therapeutic window)

key papers

1
FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high