DeFi

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.