{"entity":{"id":"defi","kind":"trial","name":"DeFi","aka":[],"tldr":"The first randomised trial to show a drug controls desmoid tumours, with better pain and function.","summary":"DeFi, trial NCT03785964 sponsored by SpringWorks and published in the New England Journal of Medicine in 2023, was the first randomised trial to show that a drug controls desmoid tumours, with better pain and physical function. It randomised 142 patients with progressing desmoid tumours to the gamma-secretase inhibitor nirogacestat or placebo, met its primary progression-free survival endpoint with a very large effect, produced responses in 41 percent against 8 percent including some complete responses, and led to approval in November 2023. OnCo links it to desmoid tumour and sarcomas, nirogacestat, the Wnt and beta-catenin pathway, the bottleneck of rare cancers without markets and the idea of intermittent or stop-and-restart dosing. Whether treatment can be paused once tumours are controlled is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03785964","url":"https://clinicaltrials.gov/study/NCT03785964"}],"tags":[],"related":[],"cancers":["sarcoma"],"sections":[],"technologies":["gamma-secretase-inhibitors","kinase-inhibitors"],"targets":[],"drugs":["nirogacestat"],"companies":["springworks"],"institutions":[],"pathways":["wnt"],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03785964","phase":"3","setting":"Progressing desmoid tumours: nirogacestat vs placebo","sponsor":"SpringWorks","result":"PFS HR 0.29; ORR 41% vs 8%.","started":"2019-04-17","startedType":"actual","yearReported":2022,"enrolled":142,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"arms":[{"name":"Nirogacestat","n":70},{"name":"Placebo","n":72}],"hr":0.29,"ci":[0.15,0.55],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2210140"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Nirogacestat","value":41},{"name":"Placebo","value":8}],"source":"https://doi.org/10.1056/NEJMoa2210140"}]},"route":"/trials/defi/","neighbours":{"cancer":[{"id":"desmoid-tumour","kind":"cancer","name":"Desmoid tumour","route":"/cancers/desmoid-tumour/"},{"id":"sarcoma","kind":"cancer","name":"Sarcomas (soft tissue, bone, GIST)","route":"/cancers/sarcoma/"}],"technology":[{"id":"gamma-secretase-inhibitors","kind":"technology","name":"Gamma-secretase inhibitors","route":"/technologies/gamma-secretase-inhibitors/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"nirogacestat","kind":"drug","name":"Nirogacestat","route":"/drugs/nirogacestat/"}],"company":[{"id":"springworks","kind":"company","name":"SpringWorks Therapeutics (Merck KGaA)","route":"/companies/springworks/"}],"pathway":[{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"idea":[{"id":"idea-desmoid-intermittent-dosing","kind":"idea","name":"Intermittent or stop-and-restart nirogacestat in desmoid tumours","route":"/ideas/idea-desmoid-intermittent-dosing/"}],"bottleneck":[{"id":"b-rare-cancers","kind":"bottleneck","name":"Rare and paediatric cancers without markets","route":"/bottlenecks/b-rare-cancers/"}]}}