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Cancer drugs are usually tested at the highest dose patients can stand, and that dose sticks for life. Comparing two or more doses head-to-head before the big trial would find doses that work as well with fewer side effects.
Following FDA's Project Optimus, sponsors run randomised parallel-dose cohorts (typically two or three doses spanning the exposure-response range) in phase 2 with efficacy, tolerability and PK endpoints, before selecting the dose for registrational trials. Precedent: the post-approval randomised comparison of sotorasib 960 mg versus 240 mg, which found similar efficacy. The proposal makes randomised dose comparison the expectation, with regulators declining to accept single-dose pivotal trials for targeted agents without it.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Sotorasib, Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Wrong doses.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Sotorasib, Wrong doses, Toxicity and quality of life are undervalued.
Shares Trial modernisation roadmap: the randomised trial → platforms and adaptive designs → decentralised, pragmatic and always-on, Wrong doses, Toxicity and quality of life are undervalued.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares FDA's Project Optimus manifesto: cancer drugs are approved at doses that are too high, Wrong doses, Toxicity and quality of life are undervalued.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.
Shares Wrong doses, Toxicity and quality of life are undervalued, Small-molecule kinase inhibitors.