Project Optimus, an initiative introduced by the U.S. Food and Drug Administration’s (FDA) Oncology Center of Excellence (OCE) in 2021, has an overarching goal of shifting the paradigm of dose selection in oncology drug development [1]. It aims to move away from the traditional focus on the maximum tolerated dose (MTD) to selecting doses that minimise toxicity but maximise efficacy and tolerability.
The initiative is expected to have a significant impact on cancer drug development, improving patients’ safety by ensuring they receive doses that are both effective and well tolerated, maximising the therapeutic benefit of a drug. It also aims to streamline drug development, providing clear guidance and expectations for dose-finding studies, which could lead to more efficient and successful registration in pivotal clinical trials. However, adopting Project Optimus is a considerable undertaking, with many aspects to consider.
Practical steps of implementing Project Optimus
Preparing for Project Optimus requires drug developers to adopt a collaborative and proactive approach, carefully planning dose-finding and optimisation strategies, leveraging available data and modelling techniques as well as engaging in early discussions with regulators. This process involves several key actions that support three main objectives:
- Characterising the exposure-response relationship
- Pharmacokinetic/pharmacodynamic (PK/PD) modelling guiding optimal dose selection
- Identifying exposure-response drivers, such as patient characteristics, concomitant medications and disease stage
- Characterising the dose-response relationship
- Assessing the drug’s safety profile across different dose levels
- Conducting PK/PD analyses, assessing the dose-dependent drug exposure and efficacy
- Evaluating potential dose-dependent changes in biomarkers correlating with safety of efficacy
- Assessing anti-tumour efficacy at different dose levels using clinical endpoints
- Selecting the recommended phase II and phase III doses
- Comprehensive analyses of exposure-response, dose-response and safety assessments to determine the recommended doses
- Statistical analyses and modelling
By following these crucial steps, drug developers can effectively implement Project Optimus, leading to more accurate dose selection in pivotal trials and optimised therapeutic outcomes for oncology patients.
The role of full-service CROs in successfully adopting Project Optimus
Implementing the above steps is likely to increase the likelihood of successfully developing oncological therapies and gaining regulatory approval, which is not an easy feat. Fortunately, contract research organisations (CROs) are ideally placed to support companies looking to adopt Project Optimus due to their expertise and experience in various aspects of drug development.
By selecting the right CRO to partner with, developers gain access to the necessary expertise and capabilities required to successfully navigate the implementation process, but which aspects should they consider to ensure they make the right choice? Here are some of the key areas of expertise to evaluate:
- Clinical trial management expertise and experience in successfully designing and managing complex dose-finding trials
- Advisory board for drug development that offers expert guidance to sponsors and ensures clinical trials are aligned with Project Optimus principles
- Regulatory affairs experience to ensure robust documentation for regulatory submissions
- Clinical pharmacology capabilities for advanced dose optimisation studies methodologies
- Central laboratory services that will support biomarker development and PK/PD modelling
- Medical writing teams for effective documentation and communication of dose optimisation strategies to various stakeholders
Choosing a full-service CRO with plenty of experience in the above areas ensures the successful implementation of dose-finding studies, optimises the development of safe and effective cancer therapies and ultimately benefits patients by ensuring they receive the most appropriate and personalised treatment.
To learn more about the practical aspects of adopting Project Optimus and discover how Simbec-Orion can help you prepare for it, read our latest whitepaper.
Reference
1. https://link.springer.com/article/10.1007/s43441-023-00606-1