ASCO Seeks Clarity from FDA Draft Guidance to Improve Trials for Accelerated Approval

The Association for Clinical Oncology (ASCO) has requested additional information from the FDA prior to finalizing their draft guidance which aims to improve oncology clinical trials for accelerated approval.¹

Some of these include plans for setting benchmarks and determining expected target dates for sponsors of confirmatory trials.

“This draft guidance is timely and important. Criticism of the accelerated approval pathway has increased as multiple drugs approved under this mechanism remain on the market without completion of confirmatory studies.” wrote Lori J. Pierce, MD, FASTRO, FASCO, then-Chair of the Board for ASCO, in a press release.

In March 2023, the FDA issued a draft guidance regarding trial design for studies whose purpose is to support accelerated approval of oncology therapeutics. The FDA stated that their preference is for randomized controlled trials over single-arm trials.²

The draft highlights the reasons the FDA supports the randomized clinical trial design, which compares new therapeutics with a currently available therapy, vs single-arm trials. Some of the key challenges and considerations for design and analysis of such trials to justify accelerated approval of new agents are also listed in the guidance.

In the draft guidance, it is made clear that studies intended to verify clinical benefit must be underway prior to approval. However, comments from those at ASCO state that the guidance does not include FDA’s perspective on expediting withdrawals.¹ They believe that this will be beneficial for the public and sponsors to clearly understand the process for the withdrawal of an indication or therapy from the market.

Another area ASCO commented on was regarding the use of randomized controlled vs single-arm clinical trial designs. ASCO agrees with the FDA that there are limitations with the use of single-arm trials. However, they noted that there are situations where other trial designs are appropriate and should be considered. An example of this is with single arm trials that may be useful for patients with rare disease types, or among patients who have suboptimal standard treatment options.

For considerations for 2 randomized controlled clinical trials, the Association said more education is needed regarding the accelerated and conditional approval processes. This will help the public further understand that the withdrawal of a therapy or an indication should not be viewed as a failure of the program.

The Association also agrees with the FDA’s perspective that sponsors should have the confirmatory trials started once the accelerated approval marketing application is submitted. This will ensure more timely completion of the studies, as well as keep away from the challenges for when there is a large use of the drug in clinical practice and patients do not enroll in trials.

Other things the Association agrees with in the guidance include that regarding considerations for a single randomized controlled trial to support accelerated approval and confirm clinical benefit, sponsors should have measures in place to prevent factors that may threaten the results from the trial. This may include blinding of data for end points supporting verification of clinical benefit. They also agree with the FDA that it is important to strive to perform efficacy analyses to support accelerated approval once a trial is close to or fully enrolled, as it will mitigate accrual challenges that could occur if the treatment receives accelerated approval.

ASCO also reinforced its stance regarding considerations for a single-arm trial to support accelerated approval by saying that there should be considerations for the use of single-arm trials when appropriate. They stated that overall survival should be the standard end point considered for measuring clinical benefit.

In addition, the Associated noted that there are many ways to evaluate benefits to patients. Quality of life and appropriate standardized criteria, such as RECIST, should be utilized when measuring objectives.

REFERENCES:

1. ASCO shares recommendations for FDA draft guidance to improve clinical trials for accelerated approval. News release. ASCO. June 5, 2023. Accessed June 9, 2023. https://tinyurl.com/3vupb94p

2. FDA issues draft guidance aimed at improving oncology clinical trials for accelerated approval. News release. FDA. March 24, 2023. Accessed June 9, 2023. https://bit.ly/3FXh6JM