What is Project FrontRunner?

Project FrontRunner, initiated by the FDA in November 2022, represents a pivotal shift in the development of cancer therapies. The objective of this initiative is to accelerate investigations of novel therapies in earlier metastatic treatment settings.

This innovative program encourages pharmaceutical and biotech companies to embark on investigations of cancer treatments and therapies in patients with earlier stages of metastatic disease.

Traditionally, these organizations have primarily focused on late-stage cancer patients for drug development, making Project FrontRunner a groundbreaking change in the industry's approach.

As part of this initiative, FDA’s Oncology center of excellence (OCE), aims to propose a framework to identify clinical development programs that may benefit numerous patients earlier in the course of their disease to strengthen data for an adequate benefit-risk assessment of the therapy.?

The core objective of Project FrontRunner is to provide patients with earlier access to safe and effective therapies during the initial course of their disease. Rapid advances in our understanding of the molecular basis of disease are leading to the development of innovative new therapies to treat disease, and thus has led to significant growth of novel therapies.

With a substantial number of newly diagnosed cancer patients each year, this initiative ensures a larger patient population can benefit from these treatments compared to the relatively smaller late-stage patient group.

There are several key advantages to this initiative:

• Earlier Access: Patients diagnosed with cancer every year can access effective and safe therapies at an earlier stage of their disease. This is particularly beneficial because late-stage patients are fewer in number.

• Extended Clinical Trial Durations: Clinical trials conducted with patients in later stages of the disease tend to be shorter due to the unpredictability of patient lifespans. Investigating therapies at an earlier stage provides a more significant patient population, allowing for longer, more comprehensive trials.

• Elucidates and compared therapeutic effect of oncology therapies to the established standard of care: Randomized controlled trials which are the gold standard in characterizing new drug safety and effectiveness are less challenging to conduct early in the course of advanced/metastatic disease (e.g., first or second line setting) due to larger patient numbers and identifiable effective treatments to compare the new drug to, factors which may lacking in a more advanced treatment setting.

• Greater Therapeutic Efficacy: Treating cancer at an earlier stage increases the likelihood of effective therapy, as there are fewer confounding factors compared to late-stage treatments, where prior therapies and other bodily mechanisms may interfere.

• Safer Alternatives: Late-stage cancer patients often receive harsh treatments such as chemotherapy. Exploring therapies at an earlier stage offers the opportunity to investigate less toxic and safer treatment options.

• Comparative Analysis: Project FrontRunner allows for the comparison of standard therapies used in late-stage patients with newer therapies. This comparison helps assess the safety and efficacy differences between earlier and later treatment settings.

Project FrontRunner also offers a unique opportunity to evaluate therapies at an earlier stage when there is a higher chance of them being effective in altering the course of the disease.?

Furthermore, it presents the potential to introduce less toxic and safer alternative therapies compared to the harsh treatments often administered to late-stage patients. Finally, it allows for a comparative analysis of standard therapies with newer treatments, shedding light on differences in safety and efficacy between earlier and later disease stages.?

While the FDA doesn't intend for this initiative to replace late-stage investigations, it encourages companies to consider the advantages of early-stage research alongside their ongoing efforts in late-stage therapy development. Project FrontRunner will be helpful to strengthen the evidence database for cancer therapies by encouraging trial designs and clinical/regulatory development (e.g., accelerated approval pathway) to generate data from gold standard randomized controlled trials to support development of safe and effective cancer therapies for millions of patients.?

What benefits does Project FrontRunner bring to key stakeholders??

The FDA's vision with Project FrontRunner is to revolutionize cancer therapy development by encouraging investigations into treatments at earlier metastatic disease stages. This initiative holds numerous advantages for various stakeholders, including patients, pharmaceutical and biotech companies, and regulatory professionals

• Patients: Patients are the foremost beneficiaries of Project FrontRunner. They gain earlier access to safe and effective therapies, increasing their chances of successful treatment when the disease is in its initial stages. This is particularly significant for cancer patients, as early intervention can be life-saving.
• Pharmaceutical and Biotech Companies: These organizations stand to gain several benefits. By conducting clinical trials in earlier settings, they can obtain more comprehensive and accurate data on therapy effectiveness. This data can improve decision-making and strategy development. Comparing therapies in early and late stages provides insights that help refine treatment approaches. Furthermore, the potential for accelerated approval pathways allows companies to bring promising treatments to market faster, potentially reducing development timelines.
• Regulatory Professionals: Regulatory experts and professionals benefit by obtaining a deeper understanding of how therapies perform in different disease stages. This information is vital for improving regulatory processes and enhancing decision-making related to drug approvals.

How about the timelines of this initiative??

Regarding timelines, Project FrontRunner doesn't alter the fundamental phases of clinical trials, which can still take several years, including Phase 1, Phase 2, and Phase 3 studies. However, it offers the potential for expedited development and approval processes, particularly in oncology and other areas with unmet clinical needs.

1. Accelerated Approval: Companies can choose to pursue accelerated approval if they achieve positive results with their therapies. This pathway is notably faster than the regular approval process and is especially critical in oncology where patients require timely access to effective treatments. While accelerated approval can't eliminate the need for comprehensive clinical trials, it allows for a quicker path to market.

1. Breakthrough Designation Approval: Similar to accelerated approval, the Breakthrough Designation path is for therapies demonstrating remarkable efficacy in areas with unmet clinical needs, such as oncology. This designation streamlines the approval process, offering an expedited route for promising treatments.

These accelerated approval pathways present an opportunity to expedite drug development and approval, potentially shortening the timeline from development to market availability. While clinical trial phases remain essential, these FDA mechanisms provide a means to ensure that promising therapies reach patients more swiftly, which is especially crucial in critical medical areas like oncology.

OCE’s Project FrontRunner and the proposed framework for advancing investigation of novel therapies in earlier treatments settings holds great promise to provide access of safe and effective therapies to millions of patients earlier in the course of their disease.?

Frequently Asked Questions

1. How soon would Project Front Runner be implemented by industry and research institutions?

Project FrontRunner is an initiative introduced by the Oncology Center of Excellence in Nov 2022. Industry professionals have started discussions on a potential proposal for clinical development of therapies. It should take months before we see clinical data generated on development of drugs and small molecules.?

1. Would we be able to see significant participation from patients in early metastatic phase for? generating clinical trial data?

We hope to see participation from cancer patients in their early disease stage as there are millions of patients looking for treatments as their disease gets detected in the early phase so they can get adequate therapies that can prevent progression of their disease.?

1. Where can you see more details of the project FrontRunner?

Project FrontRunner initiative is available on the FDA website Project FrontRunner.

About the Author

Dr. Astha Khanna, PhD. Head – Product Development & Regulatory Affairs

Dr. Khanna holds a PhD in bioengineering and has extensive research and regulatory experience in development of novel therapies for various therapeutic areas such as cardiovascular, oncology etc. She is passionate about science and contributing to global development programs involving communication with health authorities such as US FDA to bring safe and effective therapies to patients.