The Desmoid Tumor Research Foundation

Breaking News: Springworks Therapeutics Announces Topline Results From Phase 3 DeFi Trial

Clinical Trials

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On May 24, 2022, SpringWorks Therapeutics announced topline results from their Phase 3, double-blind, placebo-controlled trial called the DeFi trial. This trial evaluates the gamma secretase inhibitor, nirogacestat, for efficacy, safety and tolerability in adult patients with progressing desmoid tumors.

The DeFi trial’s primary endpoint was met by improving progression-free survival (PFS) for usage of nirogacestat compared to placebo, with a 71% reduction in the risk of desmoid tumor progression.

SpringWorks Therapeutics expects to present additional data at an upcoming medical conference as well as submit a New Drug Application (NDA) to the U.S. Food and Drug Administration in the second half of 2022.

From SpringWorks Therapeutics’ press release:

“‘Desmoid tumors are aggressive soft-tissue tumors that can lead to severe negative outcomes for patients, including long-lasting pain, disfigurement, and amputation. In rare cases, when vital organs are impacted, desmoid tumors can also be life-threatening,’ said Saqib Islam, Chief Executive Officer of SpringWorks. ‘Today’s announcement represents a significant milestone towards our goal of bringing the first approved therapy to the desmoid tumor community. We look forward to sharing the DeFi trial data with the FDA and to presenting detailed study results at a medical meeting later this year.’”

The DTRF would like to express our gratitude to members of the community who have participated in and are currently enrolled in clinical trials, including the DeFi trial. Your participation is advancing our understanding of desmoid tumors and bringing us closer to improved treatments for all desmoid tumor patients.

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As many patients know first-hand, “Response Evaluation Criteria in Solid Tumors” (known as RECIST) – a standard methodology of measuring a patient’s tumor response to treatment – is not always the best method to measure treatment outcomes for desmoid patients.

RECIST criteria are used in clinical trials to assess if a tumor is progressing, stable, or responding to treatment. RECIST is strictly measurement-based and does not factor in other positive indicators that do not involve changes in tumor size. Additionally, RECIST relies on certain measurements to monitor response – such as “longest dimension” – which may not accurately reflect the typical response of desmoid tumors to treatments.

To address this issue, the DTRF and members of its Advisory Boards have formed a working group with top radiologists, as well as pharmaceutical medical professionals who design clinical trials for desmoid patients. This working group will potentially help define other imaging features beyond RECIST that can be used to better evaluate patient outcomes.

The first working group meeting held earlier this week was a resounding success. We would like to thank our working group chairs, Drs. Mrinal Gounder and Larry Schwartz, for hosting this meeting which will impact the future of radiology in desmoid tumors.

This is an ongoing project and we will keep the community updated as it develops.


Learn more about the Radiomics Working Group

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DTRF’s Efforts Enable Largest Clinical Study On Desmoid Tumors, And New England Journal Of Medicine Publishes Breakthrough Study Results

(New York, NY) – Thursday, December 20th, 2018 – The efforts of The Desmoid Tumor Research Foundation (DTRF) enabled the largest clinical study ever in desmoid tumors. The New England Journal of Medicine just released the breakthrough study results in their December 20, 2018 article, “Sorafenib for Advanced and Refractory Desmoid Tumors.”

To date, there are no approved drugs for desmoid tumors. This international study, a first of its kind, showed that patients treated with sorafenib reduced the risk of tumor growth or death by 7-fold, which are groundbreaking results.

In 2010, when the DTRF heard news of promising results from a small pilot study conducted by Dr. Mrinal Gounder at Memorial Sloan Kettering Cancer Center with 26 desmoid tumor patients responding to sorafenib, they wasted no time in encouraging him to set a Phase III clinical trial in motion. Dr. Gounder then began a series of conversations with the FDA and the National Cancer Institute to start an international trial in this rare cancer with the purpose of getting sorafenib approved for patients with desmoid tumors.

It took over three years of efforts to finally open this study as there were countless barriers to conducting a study in a rare cancer. The Phase III study, which opened in 2014 across the United States and Canada, accrued 87 patients, a remarkable number for an ultra-rare cancer. Due to the tireless efforts of the DTRF founders, Jeanne Whiting and Marlene Portnoy, the The DTRF played a significant role in the recruitment for the trial, filling it in half the time expected–
a record time of just under 17 months.

This enabled the first clinical trial of its kind on desmoid tumors, and one of the largest Phase III clinical trials on a rare disease, to take place. Prior to this study, many cancer experts had declared that conducting a trial like this would be impossible or futile in desmoid tumors. The implications of this study are immense as researchers now try to identify how research in desmoid tumors can be applicable to fighting other types of cancers, particularly colon cancer which is a leading cause of death worldwide.

The DTRF’s efforts also played a role in moving forward another investigational treatment that was “stuck” on the shelves of a large pharmaceutical company after being deprioritized for business reasons. Nirogacestat, a gamma secretase inhibitor, showed encouraging results in a Phase II study sponsored by the NCI. However, the drug’s clinical development program was halted by the pharmaceutical company. The DTRF advocated for nirogacestat because it showed such promise and patients with desmoid tumors had limited treatment options. SpringWorks Therapeutics was then conceived by Pfizer as an innovative way to advance investigational therapies that may hold significant promise for underserved patients.

In just a year since the company’s formation, nirogacestat received fast-track designation from the FDA and SpringWorks is preparing to start a Phase III study in adult patients with desmoid tumors in the first quarter 2019. Once again, when nirogacestat showed promising results in an early study, the two fearless women who co-founded the DTRF advocated to move the drug forward. They galvanized the patient community they had built and filled up the Phase II trial in record-time, enabling SpringWorks to be able to spring into action with a Phase III trial to deliver treatments to patients who are in great need and without alternatives.

With the support of the DTRF’s efforts, there also will be two additional clinical trials on desmoid tumors in 2019. For a rare disease with an incidence rate of 5-6 per million, these are remarkable accomplishments.

For more information on The Desmoid Tumor Research Foundation please visit www.dtrf.org.

About The Desmoid Tumor Research Foundation

The DTRF was founded in 2005 with the mission of facilitating and funding desmoid tumor research and supporting patients with information. The mission of The Desmoid Tumor Research Foundation is to aggressively fund research to accelerate the development of improved therapies, and ultimately find a cure for desmoid tumors. The DTRF collaborates with dedicated researchers and clinicians worldwide to improve the lives of patients through education, awareness and support. Every year the foundation has gained momentum in its progress and has seen new clinical trials, emerging therapies and important new discoveries about the disease come to fruition.

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