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# Cavazzoni Sees ctDNA Endpoint as ‘Promising’
- URL: https://www.fdaweb.com/cavazzoni-sees-ctdna-endpoint-as-promising/
- Published: 2022-07-22T12:00:00.000Z
- Updated: 2026-09-14T17:52:59.000Z
- Author: David McFarland
- Tags: Drugs, #legacy-id-D5152341

CDER director **Patrizia Cavazzoni** says the potential use of “circulating tumor DNA (ctDNA)” as a potential endpoint to support an accelerated approval is very promising, but it requires more data to validate the biomarker for further regulatory uses. Speaking at a 7/19 Friends of Cancer Research [fireside chat](https://friendsofcancerresearch.org/event/expediting-drug-development-use-of-ctdna-as-an-early-endpoint/?ref=fdaweb.com) on the promise of ctDNA’s use as an early endpoint, Cavazzoni recommended that associated oncology clinical trials collect appropriate data on ctDNA levels “before and after drug treatment, as well as a long-term outcome data so that we can include these trials into our growing body of evidence about this promising endpoint.”

The CDER director encouraged companies to come forward and discuss and provide details about any proposed meta-analysis plan or a validation plan on the use of ctDNA in any particular context. She said ctDNA tests are also an important component because “ctDNA assessments can vary among laboratories and across technologies that are used to detect ctDNA, and so it is really important that we work toward further standardization of assays that would allow for better use of ctDNA in a regulatory context. And last but not least, I really want to emphasize the importance of collaborative approaches to validate surrogate endpoints across multiple clinical trials.”

Cavazzoni said a [guidance](https://www.fda.gov/regulatory-information/search-fda-guidance-documents/use-circulating-tumor-deoxyribonucleic-acid-early-stage-solid-tumor-drug-development-draft-guidance?ref=fdaweb.com) on ctDNA was issued earlier this year, and it discusses how in the early-stage cancer setting, ctDNA may be used to “detect a certain targetable alteration, to enrich a high- or low-risk population for study in a trial, to reflect a patient’s response to treatment, or potentially as an early marker of efficacy.” It notes, she added, that the evidence to support the clinical validity or clinical utility of ctDNA varies across solid tumor malignancies, patient populations, and testing modalities. Multiple small studies have “suggested that residual ctDNA detecting molecular residual disease (MRD) after surgery or completion of standard systemic therapy confers a poor prognosis and selects a population at high risk of relapse,” according to the guidance.

During the chat, Cavazzoni was also asked to opine on the state of the accelerated approval program in general. She said it was “essential program for oncology and for other disease areas, and because of that, we need to nurture it, we need to protect it and we need to find ways to expand its use.” She acknowledged that accelerated approval has mostly been used in oncology because there are direct disease processes, like tumor size reduction or delays in progression, that can be measured quantitatively and objectively, “and that is not something that we have in many other disease areas. And these types of measures in oncology have been standardized, socialized within the research community over decades, and have been correlated with beneficial outcomes, so they have really become part of the fabric of not only research but also clinical practice. Also, in oncology, we have seen recent advances in immuno and precision oncology that have gone hand in hand with achieving a much greater understanding of the biological underpinnings of cancer, and therefore have led to drug development with unprecedented responses and duration of responses.”

To expand accelerated approval in other areas will likely require a greater understanding of the “biological underpinnings” of other diseases and the identification of surrogate markers that may serve as endpoints for accelerated approvals, Cavazzoni said. “We have made great strides in oncology, and the other ways in which we can continue to advance accelerated approval is by continuing to enhance the program, for instance, by promoting consistent, upfront discussions with companies and developers, timely initiation of confirmatory trials, and also encouraging trials that are feasible and more generalizable than the trial or trials that led to the accelerated approval.”

Cavazzoni contended that there are still opportunities to identify more endpoints to support drug development and potentially accelerated approval. “When we think about evidence generation to support the utilization of new endpoints, it is really important to distinguish the type of evidence generation that is needed to validate a surrogate endpoint that can actually replace clinical endpoints, such as hypertension replacing stroke, for instance, versus the type of evidence generation that is needed to validate a surrogate endpoint that reasonably predicts clinical benefit, and the latter is the type of endpoint that underpins the utilization of accelerated approval,” she said. “And so these are very important distinctions that very often are lost in discussions about accelerated approval endpoints, and it can make a difference when it comes to the type of evidence that’s needed to be brought to bear and the duration of the validation process and the context within which the evidence are generated.”