Clinical Summary:

• Design/Population: A real-world retrospective analysis evaluated nirogacestat versus other systemic therapies in patients with desmoid tumors.
• Key Outcomes: Nirogacestat showed a numerically higher objective response rate than comparator therapies. Progression-free survival was similar between treatment groups, and no deaths occurred during follow-up.
• Clinical Relevance: Nirogacestat demonstrates real-world activity in desmoid tumors and may offer improved tumor response compared with commonly used systemic options, though longer follow-up and larger studies are needed to confirm comparative benefit.

Results from a retrospective real-world analysis demonstrated that nirogacestat improved response compared to other commonly used systemic therapies among patients with desmoid tumors. 

“Nirogacestat, a gamma-secretase inhibitor, was recently proven effective versus placebo in a phase 3 trial and approved for desmoid tumors,” stated HeeKyung Kim, MD, PhD, UCI Health/Chungbuk National University Hospital, Orange, California, and coauthors. “We performed a real-world comparison of nirogacestat versus other systemic therapies.”

In this single-center study, researchers evaluated data from 31 patients with desmoid tumors treated between 2019 and 2025. Patients received either nirogacestat (n = 18) or standard therapies including sorafenib, pazopanib, or tamoxifen plus sulindac (n = 13). Primary end points included objective response rate (ORR) and progression-free survival (PFS). 

At analysis, the ORR was 44.4% in the nirogacestat arm and 23.1% in the standard arm, although the difference did not reach statistical significance (P = .45). Complete responses were reported in 5.6% and 7.7% of patients, respectively. Partial responses were reported in 38.9% and 15.4% of patients. 

Among responders with available follow-up data, median time to response was 6.4 months in the nirogacestat arm and 6.7 months in the standard arm. Median PFS was not reached in the nirogacestat arm and was 58 months in the standard arm (P = .686). No deaths occurred during follow-up, and overall survival was not estimable in either group.

“Nirogacestat showed a higher tumor response rate than other systemic therapies (sorafenib, pazopanib, or tamoxifen/sulindac) in this real-world analysis,” concluded Dr Kim et al. “These findings support the activity of nirogacestat in desmoid tumors and warrant validation in larger, long-term studies.”

Source:

Kim H, Chow WA. Real-world efficacy of nirogacestat compared to prior standard-of-care (SOC) systemic agents in desmoid tumors. Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract e23542.