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FDA Accelerated Approval for Oncology Therapeutics: Clinical Trial Considerations


FDA issued a guidance document in 2014 describing provisions for expedited programs for serious conditions.

In March 2023, FDA released a draft guidance specific to accelerated approval of anti-cancer drugs.  

What is accelerated approval under FDA? 

The accelerated approval pathway was established through the Food and Drug Administration Safety and Innovations Act of 2012 (FDASIA). It allows for approval of a drug to treat a serious condition using a surrogate endpoint that is likely to predict clinical benefit, if the therapy provides a meaningful benefit over existing therapies.  

FDA Accelerated Approval for Oncology Drugs 

In oncology, clinical benefit has typically been overall survival. Radiographic evidence of tumor shrinkage has been used as a surrogate endpoint for accelerated approval likely to predict an improvement in overall survival. 

While FDA considers randomized, controlled trials to be the gold standard for drug development, they acknowledge the common use of single-arm trials to establish preliminary safety and efficacy in oncology. Often, single-arm trials may include: 

  • Small safety databases 
  • Uninterpretable time-to-event efficacy endpoints 
  • Low magnitude response rates 
  • Challenges in establishing the contribution of individual components in combination regimens  

Nonetheless, in the setting of unmet medical need, promising results from these single arm studies may be sufficient to establish an appropriate risk-benefit to qualify for accelerated approval for oncology therapies. 

What are the current recommendations for FDA accelerated approval?  

The current guidance provides recommendations for conducting single-arm trials to support accelerated approval.  

  1. Sponsors should pre-specify historical trials to serve as a basis for comparison with available therapies.  

  2. The sample size should permit adequate precision, robust estimation of duration of response, and sufficient description of adverse events.  

  3. The magnitude and duration of response should be evaluated to support accelerated approval, and follow-up time should be considered for adequate characterization of response rate. 

  4. Blinded independent central review (BICR) of response assessment should be performed to reduce potential bias and mitigate variance in the assessment of response.  

  5. Post-marketing confirmatory trials are required to verify and describe anticipated clinical benefit. 


What are the requirements for FDA accelerated approval? 

Precision medicine approaches in oncology often target the expression of a biomarker. This may define a subset of patients with a particular cancer or be used to monitor response to therapy. Response to standard of care may not be well established or inherently variable in these patients. This may require a randomized controlled trial to demonstrate clinical benefit. Licensure under accelerated approval requires confirmation of clinical benefit.

The guidance document discusses the expectations of the agency

A well-designed randomized trial used for accelerated approval may be designed such that additional follow up of patients could fulfill a post-marketing requirement to verify clinical benefit. A single arm study will usually not be sufficient, given the residual uncertainties inherent in its design. A randomized controlled confirmatory trial could also be set up to evaluate a new drug in an earlier treatment setting. 

Should I pursue FDA accelerated approval?

For oncology therapies, pursuing accelerated approval can be a viable option for drugs that provide a meaningful benefit over existing therapies, especially in the setting of unmet medical need.

Keys to successful collaboration with the FDA

Successful collaboration begins with understanding the FDA guidance for designing clinical trials and early discussions with the agency. While randomized controlled trials remain the gold standard, single-arm trials can establish preliminary safety and efficacy in oncology. However, they should be well-designed, with pre-specified historical trials, adequate sample sizes and follow-up times, and blinded independent central review. By understanding the FDA guidance, sponsors can increase their chances of success in bringing safe and effective treatments to patients in need. 

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