FDA Offers New Clinical Trial Guidance for Oncology Accelerated Approval

FDA details its view of the “limitations” of single-arm trials in oncology drug development and invites comment on its favored approach going forward.  Becky Wood, Emily Marden, and Julea Lipiz explain.  

Single-arm trials commonly have been used to support accelerated approval in oncology drug development.  FDA has now announced the availability of draft guidance on “Clinical Trial Considerations to Support Accelerated Approval of Oncology Therapeutics” pointing out the “limitations” of this approach and inviting public comment on its “preferred approach” of randomized controlled trials.

FDA states that the purpose of the guidance is to “provide recommendations to sponsors of anti-cancer drugs or biological products on considerations for designing trials intended to support accelerated approval” and specifically recommends that sponsors conduct randomized controlled clinical trials. In so doing, the guidance identifies the “limitations” of single-arm trials in a list seemingly drawn from recent withdrawals or proposed withdrawals of oncology products approved through the accelerated approval pathway.

FDA acknowledges that historically, single-arm trial designs and response endpoints have most commonly been used in oncology. FDA views the limitations of such trials as including: small safety datasets; difficulty in interpreting common time-to-event efficacy endpoints (e.g., tumor progression, overall survival); low magnitude response rates generally may not be reasonably likely to predict clinical benefit; difficulty in establishing contribution of components, for combination regimes; and challenges in determining improvement over available therapy when relying on cross-trial comparisons to historical controls.

Going forward, FDA states that it generally prefers randomized controlled trials, including those that provide for longer term follow-up that could fulfill a postmarketing requirement to verify clinical benefit. According to FDA, this “one-trial” approach could be a means of addressing the challenge of enrolling a confirmatory trial once the drug is approved. Consistent with recent changes to the accelerated approval pathway introduced by Food and Drug Omnibus Reform Act of 2022 (FDORA), the guidance states that confirmatory trials should be started prior to a product’s approval.

FDA acknowledges that in some cases single-arm trials may be appropriate to support accelerated approval. The draft guidance outlines considerations for designing, conducting, and analyzing data from a single-arm trial intended to support accelerated approval when appropriate, and considerations for determining whether the data may be adequate for this purpose.

The draft guidance is important for any sponsor considering the accelerated approval pathway for oncology therapeutics. The Notice for the draft guidance is scheduled to be published on March 27, 2023, and will be open for comment for 60 days after publication.

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