Merck KGaA's long-term data from the phase-III DeFi trial shows that OGSIVEO (nirogacestat) provides sustained efficacy and safety in adults with progressing desmoid tumours.

The study, which involved a long-term open-label extension phase, demonstrated durable tumour reduction and consistent safety over time, alongside sustained improvements in patient-reported outcomes such as pain. These findings represent one of the largest prospective analyses of a randomised controlled trial for systemic treatment in desmoid tumours and confirm the long-term benefits of OGSIVEO. 

The DeFi trial was a global, randomised, multi-centre, double-blind, placebo-controlled phase-III study. The newly published long-term data, based on a December 2024 data cutoff (the final cutoff of the trial), demonstrated that extended OGSIVEO treatment was associated with additional tumour shrinkage, an increase in Objective Response Rate (ORR) with further partial and complete responses, sustained improvements in patient-reported outcomes, and a consistent safety profile compared to earlier analyses using the April 2022 cutoff.

“Desmoid tumours are locally aggressive and unpredictable, often causing significant pain, functional limitations, and emotional distress. The new JCO data provide important insights into the long-term safety and efficacy of nirogacestat. These findings can help physicians make more informed treatment decisions and further improve care for patients living with desmoid tumours,” said Ravin Ratan, MD, MEd., Associate Professor, Department of Sarcoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, and lead author of the JCO publication.

Patient-reported outcomes, including measures of pain, symptom severity, physical functioning, global health status, and role functioning, improved early in treatment (as soon as Cycle 2) and remained durable through up to 45 months of therapy.

 “We are pleased that long-term continuous nirogacestat treatment for up to four years was associated with additional late responses and further tumour size reductions. These data represent the largest prospective analysis from a randomised controlled clinical trial of long-term exposure to any systemic agent for desmoid tumours and provide valuable insights into the benefits of OGSIVEO for patients,” said Uche Iloeje, MD, Senior Vice President, Global Head of Medical Affairs, SpringWorks Therapeutics.