FDA Project Optimus: Reforming Dose Optimization in Oncology Drug Development

The FDA's Project Optimus is an initiative to reform the dose optimization and dose selection paradigm in oncology drug development. The current paradigm for dose selection is based on cytotoxic chemotherapeutics, which often leads to doses and schedules of molecularly targeted therapies that are inadequately characterized before initiating registration trials. This can result in patients receiving suboptimal doses of drugs, which can lead to decreased efficacy and increased toxicity.

Project Optimus aims to address this issue by promoting a new paradigm for dose optimization that emphasizes selection of a dose or doses that maximize not only the efficacy of a drug but the safety and tolerability as well. The FDA initiative intends to do this by educating, innovating, and collaborating with companies, academia, professional societies, international regulatory authorities, and patients.

Specific goals of Project Optimus include:

• Communicating expectations for dose-finding and dose optimization through guidance, workshops, and other public meetings.
• Developing and validating new approaches to dose optimization, such as Bayesian methods and adaptive designs.
• Promoting the use of real-world data to inform dose optimization decisions.
• Facilitating international collaboration on dose optimization research.

Project Optimus is a major undertaking, but it has the potential to significantly improve the way that oncology drugs are developed and approved. By ensuring that patients receive the right dose of the right drug, Project Optimus can help to improve the efficacy and safety of cancer treatment and ultimately save lives.

Some of the benefits of Project Optimus include:

• Increased likelihood of success in clinical trials.
• Reduced risk of toxicity.
• Improved efficacy.
• Increased quality of life for patients.
• Faster time to market for new drugs.

To use Project Optimus for your drug dose optimization plan, you will need to:

1. Understand the dose-response relationship for your drug. This means understanding how the dose of the drug affects its efficacy and toxicity. You can do this by conducting preclinical studies and clinical trials.
2. Develop a dose optimization plan. This plan should include the following:
   • The target efficacy and safety endpoints for your drug.
   • The range of doses that you will evaluate in your clinical trials.
   • The methods that you will use to assess the efficacy and toxicity of your drug at different doses.
3. Conduct clinical trials to evaluate the dose-response relationship for your drug. These trials should be designed to answer the following questions:
   • What is the optimal dose of your drug for efficacy?
   • What is the optimal dose of your drug for safety?
   • What is the relationship between dose and toxicity?
4. Analyze the data from your clinical trials to determine the optimal dose of your drug. This analysis should take into account the target efficacy and safety endpoints, as well as the results of your preclinical studies.

Here are some additional resources that you may find helpful:

• FDA Project Optimus: https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus
• Guidance for Industry: Dose Optimization in Oncology: https://www.fda.gov/media/144650/download
• Project Optimus Toolkit: https://www.fda.gov/media/144651/download