Real-World Study Shows Nirogacestat Provides Sustained Disease Control and Symptom Improvement in Patients With Desmoid Tumors

Clinical Summary:

• Design/Population: This retrospective, real-world trial evaluated nirogacestat among patients with desmoid tumors treated through the French compassionate use program. Patients had received a median of 2 previous therapies, including local treatments, and were followed for a median of 21.4 months.
• Key Outcomes: Partial responses occurred in 60% of patients and stable disease in 31%, with a 1-year progression-free survival rate of 76.2%. Among patients with baseline pain, 78% of patients experienced improvement and 71% reduced or discontinued analgesics.
• Clinical Relevance: These findings reinforce the clinical benefit of nirogacestat outside a controlled trial setting, demonstrating tumor shrinkage, durable disease control, and meaningful pain improvement in a previously treated desmoid tumor population. 

Results from the real-world DeNi trial demonstrated durable disease control, tumor responses, and pain improvement with nirogacestat in patients with desmoid tumors, with outcomes consistent with those previously reported in the phase 3 DeFi trial. 

This retrospective study evaluated 55 patients with desmoid tumors who received nirogacestat through the French compassionate use program between February and June 2024. Patients had received a median of 2 prior therapies, including local therapies.

At a median follow-up of 21.4 months, the estimated median duration of nirogacestat treatment was 16 months. Partial response was observed in 60% patients, while 31% of patients achieved stable, indicating disease control in 91% of the cohort. The 1-year progression-free survival (PFS) rate was 76.2%. At 1 year, 77% of patients remained without a treatment change, including patients who continued nirogacestat following dose reductions.

Treatment was also associated with improvements in pain and analgesic use. Among 49 patients who reported pain at baseline, 78% of patients experienced improvement in pain during nirogacestat treatment. Additionally, 71% of patients reduced or discontinued analgesic therapy.

The most frequently reported adverse events of any grade included diarrhea (53%), fatigue (47%), and rash (29%). Dose reductions were required in 13 patients, most commonly due to digestive adverse events, which accounted for 11 of the 13 dose reductions. One patient required a dose reduction for mucositis and 1 patient required a dose reduction for fatigue with hypertension.

As study authors concluded, “the DeNi study confirms the clinical benefits of nirogacestat in patients with desmoid tumors, with improvements in pain and tumor shrinkage observed in 60% of patients and PFS consistent with that reported in the phase 3 DeFi trial.” 

Source:

Kubicek P, Guérin‐Charbonnel C, Toulmonde M, et al. DeNi study: Real‐world data on the use of nirogacestat in patients with desmoid tumors in the French Sarcoma Group. Int J Cancer. Published online: July 28, 2026. doi:10.1002/ijc.70672