The Oncology Center of Excellence (OCE) Project Optimus is an initiative to reform the dose optimization and dose selection paradigm in oncology drug development. Too often, the current paradigm for dose selection—based on cytotoxic chemotherapeutics—leads to doses and schedules of molecularly targeted therapies that are inadequately characterized before initiating registration trials.
Patients may be receiving these novel therapeutics for longer periods of time to maximize the benefit of a drug, which ideally includes not only longer survival but also an improved quality of life.
Poorly characterized dose and schedule may lead to selection of a dose that provides more toxicity without additional efficacy, severe toxicities that require a high rate of dose reductions, intolerable toxicities that lead to premature discontinuation and missed opportunity for continued benefit from the drug, and potentially persistent or irreversible toxicities that limit the options for receiving benefit of subsequent therapies—to name a few examples.
The goal of Project Optimus is to educate, innovate, and collaborate with companies, academia, professional societies, international regulatory authorities, and patients to move forward with a dose-finding and dose optimization paradigm across oncology that emphasizes selection of a dose or doses that maximizes not only the efficacy of a drug but the safety and tolerability as well.
Specific Goals include:
- Communicate expectations for dose-finding and dose optimization, through Guidance, workshops, other public meetings
- Provide opportunities for and encourage drug developers to meet with FDA Oncology Review Divisions early in their development programs, well before conducting trials intended for registration, to discuss dose-finding and dose optimization.
- Develop strategies for dose finding and dose optimization that leverages nonclinical and clinical data in dose selection, including randomized evaluations of a range of doses in trials. An emphasis of such strategies will be placed on performing these studies as early as possible in the development program and as efficiently as possible to bring promising new therapies to patients.
Optimus leads are Drs. Mirat Shah and Atik Rahman, and a wide range of expertise is represented among the entire project team including medical oncologists, clinical pharmacologists, pharmacologists-toxicologists, statisticians.
- Shah M, Rahman A, Theoret MR, Pazdur R. The Drug-Dosing Conundrum in Oncology - When Less Is More. N Engl J Med. 2021 Oct 14;385(16):1445-1447. doi: 10.1056/NEJMp2109826. Epub 2021 Oct 9. PMID: 34623789.
- Friends of Cancer Research White Paper. Optimizing Dosing in Oncology Drug Development. Friends of Cancer Research Annual Meeting 2021.
FDA Guidance Documents
- Population Pharmacokinetics
- Exposure-Response Relationships — Study Design, Data Analysis, and Regulatory Applications
- ICH Topic E4: Dose-Response Information to Support Drug Registration