In 2021, Project Optimus was launched by the U.S. Food and Drug Administration’s (FDA) Oncology Center of Excellence (OCE) to help oncology drug developers target dose optimisation and guide selection processes. Here, we answer some of the most pressing questions developers may have about the initiative.
1. What is the aim of Project Optimus?
The primary aim of the project is to change the paradigm of early oncology drug development. It aims to ensure that cancer drugs are developed and tested using more than one dose that could not only be effective in fighting the disease but also be safer or more tolerable for patients. Too often, the current approach, based on the maximum tolerated dose (MTD) leads to doses that may be too high, causing unnecessary side effects and potentially leading to less or noncompliance, or too low, not providing enough benefit.
Project Optimus sets out to achieve its aims through:
- Educating companies, researchers and regulators about dose optimisation strategies
- Innovating by encouraging the use of novel methods for determining optimal doses
- Collaborating with various stakeholders to implement these changes across the field of oncology
2. What is the Project Optimus framework for dose optimisation and selection processes when developing oncology drugs?
Project Optimus promotes a framework that prioritises the exploration of several potentially effective doses, rather than focusing solely on the MTD. This involves the following:
- Communicating dose-finding and dose-optimisation expectations: Providing guidance, workshops and public meetings to establish clear expectations for dose finding and optimisation
- Initiating early engagement:Inviting oncology drug developers to engage with the FDA Oncology Division early in the programme to discuss dose-finding and optimisation strategies
- Developing efficient dose-finding strategies: Using approaches for non-clinical and clinical data for dose determination, including randomised assessments of dose ranges and prioritising early implementation of strategies to expedite the delivery of promising therapies to patients.
3. What is the intended impact of Project Optimus?
The impact is multifaceted, aiming to bring about positive changes in the development and use of oncology drugs, including:
- Improved safety and tolerability: By encouraging the selection of doses that better balance efficacy with safety, Project Optimus aims to reduce unnecessary side effects that can be brought about by choosing MTD. This will improve the safety and tolerability of the treatment, increasing the chance of better compliance and hence improving overall patient experience.
- Enhanced efficacy: By identifying optimal doses that maximise the therapeutic benefit of a drug beyond tumour response (“shrinkage”), Project Optimus hopes to improve treatment outcomes for patients and increase compliance, improving the drug’s efficacy. This could mean longer survival, better disease control or improved quality of life.
- Patient-centric approach: The focus on patient-reported outcomes and quality of life emphasises the importance of patient well-being throughout the drug development process. This ensures treatment decisions are made with the patient’s best interests in mind.
- Optimised drug development: By promoting early and continuous dose optimisation, Project Optimus aims to streamline the drug development process, potentially leading to the faster and more efficient development of new cancer treatments, with fewer post-marketing requirements (PMRs), such as having to conduct additional trials or studies.
- More informed decision-making: By incorporating pharmacokinetic/pharmacodynamic (PK/PD) data and other relevant information, Project Optimus encourages more informed decision-making around dose selection. This ensures that both patients and healthcare professionals have a better understanding of the benefits and risks of different doses.
Overall, the intended impact of Project Optimus is to revolutionise the way oncology drugs are developed and used, ultimately leading to safer, more effective and more patient-centric cancer treatment.
4. Is implementing Project Optimus financially viable?
Although adopting the project may require some initial investment in terms of implementing new methodologies and adapting existing processes, the potential long-term financial benefits make it a compelling proposition for oncology drug developers. Moreover, the positive impact on patient outcomes and overall healthcare efficiency reinforces the value of this investment.
An important aspect of the big picture is the FDA’s focus on the need for sponsors to conduct post-marketing trials after drugs are approved. These studies or trials aim to obtain additional information on the optimum dosage of a product where the MTD was previously used along with further insights into safety and efficacy. These include PMRs and post-marketing commitments (PMCs), which have shown the need for a changed approach to dose optimisation. Under Project Optimus, the requirement for additional PMRs and PMCs is greatly reduced.
5. What role can CROs play in implementing Project Optimus?
Full-service, experienced CROs can play a crucial role in implementing Project Optimus for oncology drug developers due to their extensive expertise and capabilities across various stages of drug development as well as their knowledge and experience in applying Project Optimus principles in their studies. By partnering with the right CRO, oncology drug developers can leverage their expertise and resources to efficiently and effectively implement Project Optimus principles, accelerating the development of safer and more effective cancer treatments while minimising costs and risks.
Would you like to know more about Project Optimus and how CROs can help implement it? Read our recent whitepaper, Primed for Optimus: Taking a proactive approach to Project Optimus, or contact us directly to learn how we can help you prepare for adopting this initiative in your endeavours.