# DeFi

Source: https://onco.cc/trials/defi/  
OnCo record `defi` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03785964
- Phase: 3
- Setting: Progressing desmoid tumours: nirogacestat vs placebo
- Sponsor: SpringWorks
- Enrolled: 142
- Result: PFS HR 0.29; ORR 41% vs 8%.
- Outcomes: Progression-free survival: Nirogacestat vs Placebo, HR 0.29; Objective response rate: Nirogacestat 41% vs Placebo 8%

## Sources

- ClinicalTrials.gov NCT03785964: https://clinicaltrials.gov/study/NCT03785964

## Connected records

- cancers: [Desmoid tumour](https://onco.cc/cancers/desmoid-tumour/), [Sarcomas (soft tissue, bone, GIST)](https://onco.cc/cancers/sarcoma/)
- technologies: [Gamma-secretase inhibitors](https://onco.cc/technologies/gamma-secretase-inhibitors/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- drugs: [Nirogacestat](https://onco.cc/drugs/nirogacestat/)
- companies: [SpringWorks Therapeutics (Merck KGaA)](https://onco.cc/companies/springworks/)
- pathways: [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- ideas: [Intermittent or stop-and-restart nirogacestat in desmoid tumours](https://onco.cc/ideas/idea-desmoid-intermittent-dosing/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)

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JSON: https://onco.cc/api/v1/entities/defi.json