Understanding FDA's Project Optimus

Project Optimus is an initiative from the FDA Oncology Center of Excellence led by Drs. Mirat Shah and Atik Rahman. The goal of the initiative is to educate, innovate, and collaborate with the oncology community - including companies, academia, professional societies, international regulatory authorities, and patients - to advance a dose-finding and dose-selection paradigm that emphasizes the selection of an optimal dose (or doses) in the pre-market setting. An optimal dose is defined as a dose that maximizes the benefit/risk profile or provides the desired therapeutic effect while minimizing toxicity. 

Given the high risk for patients and severity of oncologic disease, historically there has been more leniency and tolerability for toxicity of experimental treatments, with a “more is better” mentality to dosing. As the landscape of oncology treatments has shifted from cytotoxic chemotherapies to other types of novel therapeutics, including molecularly targeted therapies which often have a wider therapeutic index, this mentality is not always appropriate. Sometimes, a lower dose may be as effective with less toxicity, allowing patients to tolerate the treatment better and for longer durations. Selection of an optimal dose during the drug development process is essential, as inadequate dosing can lead to failure to bring a drug to market​, including impact on the success of the registrational trial, and high frequencies of dose modifications or lack of adherence at approved doses, leading to lack of benefit for patients.  

A draft Guidance for Industry titled “Optimizing the Dosage of Human Prescription Drugs and Biological Products for the Treatment of Oncologic Disease” was published in January 2023. The intention of the guidance is to assist sponsors in the process of identifying the optimal dose(s) for human prescription drugs or biological products in oncology​. In conjunction with publications from the Project Optimus initiative, this guidance should be considered by sponsors in evaluating their clinical development plans in oncology.  

​Sponsors with novel oncology therapies, including those in development under an FDA expedited program, should expect to discuss their dose optimization strategy with the FDA. The strategy can be implemented at multiple points within the clinical development program, the timing of which is dependent on the volume of data already collected, the current stage of the development, and the type of treatment.  

For further reading and publications by the initiative, visit the Project Optimus website: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus 

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