Blog Post

How Project Optimus has Reshaped Oncology Drug Development: Opportunities and Challenges

May 23, 2024

Divya Walia
Engagement Manager
Dr. Cameron Mackenzie
Vice President

In the wake of the FDA’s Project Optimus, an initiative to reform the current approaches to dose selection and dose optimization for oncology drugs, the clinical development of cancer therapies will likely undergo a prolonged and costly transition from the conventional paradigm. While the new approaches are geared toward yielding better-tolerated drugs, these changes require additional resources and could lead to fewer drugs reaching the market.

As the FDA’s guidelines for drug development and accelerated approvals in oncology continue to evolve in favor of patient centricity, these changes pose certain challenges for drug developers and clinical trial sponsors. In 2021, the FDA launched Project Optimus1, signaling a strategic shift toward reforming the dose optimization and dose selection paradigm in oncology. This endeavor gained momentum through a collaborative FDA-ASCO workshop2 in May 2022, followed by an FDA draft guidance document3 in January 2023.

Project Optimus represents a significant attempt to revolutionize dose-finding and dose-optimization strategies early in the clinical development of oncology drugs. Before the launch of Project Optimus, dose-finding studies predominantly relied on the maximum tolerated dose (MTD) paradigm, which was originally designed for cytotoxic chemotherapy. However, this approach is grounded in linear dose response and focuses on severe dose-limiting toxicities (DLTs), often resulting in poorly tolerated drugs and adversely impacting patients’ quality of life. As the treatment landscape for patients with cancer has shifted toward diverse dose-response relationships through targeted and novel therapies, it has become imperative to recognize the limitations of the MTD approach. As a result of Project Optimus, the FDA emphasizes the necessity of conducting tailored dose-finding studies that explore a spectrum of doses to find a balance between a drug’s efficacy and safety and allow for a subsequent evaluation of the selected doses. This strategic shift aligns with the evolving nature of oncology therapeutics, promoting a more nuanced and informed approach to identifying optimal dosage regimens and resulting in safer, better-tolerated drugs overall.

Strategic considerations in dose optimization for balancing efficacy, safety and patient outcomes: Key takeaways from the FDA’s guidance document

Case studies under Project Optimus

Implications for the industry: Improved drugs with a time and resource cost

More drugs vs. better drugs

To mitigate the adverse effects and poor quality of life associated with some current cancer therapies, regulatory bodies are intensifying their efforts to balance the safety and efficacy of oncology drugs, with the FDA going a step further in defining these therapies’ risk-benefit profiles. While the evolving parameters in drug development promise enhanced safety and responsiveness to patient needs, there is an inevitable trade-off: Fewer drugs will reach the market due to the need for increased investment and time. This presents a dilemma for pharmaceutical companies: They can choose to progress quickly with increased financial investment, or they take a more measured, stepwise approach that comes with the risk of falling behind their competitors.