A study to learn if nirogacestat works and is safe for adult participants with desmoid tumors: a plain language summary of the DeFi study
- PMID: 40070345
- PMCID: PMC11952124
- DOI: 10.1080/14796694.2025.2462519
A study to learn if nirogacestat works and is safe for adult participants with desmoid tumors: a plain language summary of the DeFi study
Plain language summary
What is this summary about?This is a summary of the DeFi study, published in The New England Journal of Medicine in March 2023. In the DeFi study, researchers were studying if the drug called nirogacestat (Ogsiveo®) could slow disease progression and improve disease symptoms. The study included 142 adults with progressing desmoid tumors.In summary, what were the DeFi study results?In this study, researchers found that: Nirogacestat reduced the chance of a participant’s disease getting worse during the study by 71% compared with a placebo.41% of the participants had their tumors respond to treatment with nirogacestat. 7% of the participants had their tumors disappear completely and 34% of the participants had their tumors shrink by at least 30% during the study.Participants who took nirogacestat had significant reduction of pain and disease-related symptoms, improvement in their ability to perform daily activities, and improvement in their overall quality of life compared with participants who took a placebo.Almost all participants who took nirogacestat had side effects, and most side effects were mild or moderate.Among participants who received nirogacestat, the most common side effects were diarrhea, nausea, fatigue, low levels of phosphate in the blood (hypophosphatemia), and rash.75% of women expected to be able to have children who took nirogacestat had ovarian toxicity. Ovarian toxicity was identified and reported by researchers based on abnormal blood hormone levels or symptoms associated with the onset of menopause, such as missed menstrual periods. Among women who had ovarian toxicity, researchers reported that 74% had their ovarian toxicity resolve, including in 100% of those women who stopped taking nirogacestat for any reason. –4 participants stopped treatment with nirogacestat due to ovarian toxicityWhat do the results mean?Nirogacestat helped to shrink desmoid tumors, decrease pain, decrease the severity of symptoms related to desmoid tumors, improve the ability to perform daily activities, and helped improve overall quality of life in participants more than a placebo. Participants taking nirogacestat experienced more side effects than participants taking a placebo.[Box: see text].
Conflict of interest statement
B. Kasper reports having received consulting fees from Ayala Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, GSK, PharmaMar, Regeneron Pharmaceuticals, and SpringWorks Therapeutics, Inc. R. Ratan reports having received funding paid to his institution from Ayala Pharmaceuticals, C4 Therapeutics, and SpringWorks Therapeutics, Inc., as well as fees for medical advisory boards from Bayer HealthCare Pharmaceuticals Inc., Epizyme Inc., and SpringWorks Therapeutics, Inc. A. Lim, and S. Cho are employees of SpringWorks Therapeutics, Inc., and report receiving stock and stock options. J. Han is a former employee of SpringWorks Therapeutics, Inc., and reports having received stock and stock options. S. Kummar reports having received consulting fees from Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim, Cadila, Gilead Sciences Inc., Harbour Biomed, MundiBiopharma, Oxford Biotherapeutics, and SpringWorks Therapeutics, Inc., as well as stock from Arxeon and Pathomiq, as well as fees for data and safety monitoring from Mirati. M. Gounder reports having received consulting fees from Ayala Pharmaceuticals, Bayer Healthcare, Boehringer Ingelheim, Epizyme Inc., Karyopharm Therapeutics, Rain Therapeutics, Regeneron Pharmaceuticals, and SpringWorks Therapeutics Inc., as well as grants from the Food and Drug Administration and the National Cancer Institute. Desmoid Tumor Research Foundation reports receiving grants and sponsorship from SpringWorks Therapeutics, Inc. Sarcoma Patient Advocacy Global Network reports receiving grants and sponsorship from SpringWorks Therapeutics, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Medical writing and editorial assistance in the development of this summary were provided by Zack Fey and Matt Chapman of the Center for Information & Study on Clinical Research Participation (CISCRP), a non-profit organization focused on educating and informing the public about clinical research participation. Medical writing and editorial assistance were funded by SpringWorks Therapeutics, Inc.
Patient reviewers on this PLSP have received honorarium from
Update of
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Nirogacestat, a γ-Secretase Inhibitor for Desmoid Tumors.N Engl J Med. 2023 Mar 9;388(10):898-912. doi: 10.1056/NEJMoa2210140. N Engl J Med. 2023. Update in: Future Oncol. 2025 Apr;21(8):889-901. doi: 10.1080/14796694.2025.2462519. PMID: 36884323 Free PMC article. Updated. Clinical Trial.
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