Behind the DeFi Trial: Nirogacestat for Patients With Desmoid Tumors

Bernd Kasper, MD, PhD, professor, Universitätsmedizin Mannheim, Mannheim, provides an overview of the phase 3 DeFi trial (NCT03785964) which evaluated nirogacestat (Ogsiveo) for the treatment of patients with progressing desmoid tumors.

In the global, randomized, multicenter, phase 3 trial, investigators evaluated the primary end point of progression-free survival (PFS).

In November 2023, the FDA approved nirogacestat based on the findings from DeFi.¹ Here, nirogacestat reduced the risk of disease progression or death by 71% vs placebo among patients with desmoid tumors (HR, 0.29; 95% CI, 0.15-0.55; P < .001).² Of the patients treated with nirogacestat (n = 70), the Kaplan-Meier-estimated median PFS was not estimated. For patients treated with placebo (n = 72), the median PFS was 15.1 months (95% CI, 8.4-not estimable). The likelihood of being event-free at 1 year was higher among patients treated with nirogacestat vs placebo, at 85% (95% CI, 73%-92%) and 53% (95% CI, 40%-64%), respectively.

Other findings from the study showed that at 2 years, event-free survival rates were 76% (95% CI, 61%-87%) with nirogacestat and 44% (95% CI, 32%-56%) with placebo, respectively. The confirmed overall response rate was 41% with nirogacestat vs 8% with placebo (P < .001), and the complete response rates were 7% and 0%, respectively. The median time to confirm first response was 5.6 months and 11.1 for the nirogacestat arm vs control arm, respectively, and the median best percent change in target tumor size was -27.1% (range, -100 to 37) vs 2.3% (range, -100 to 47).

References

1. FDA approves nirogacestat for desmoid tumors. News release. FDA. November 27, 2023. Accessed March 25, 2025. https://tinyurl.com/mwyyeeeh

2. Gounder M, Ratan R, Alcindor T, et al. Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med. 2023;388(10):898-912. doi:10.1056/NEJMoa2210140