FDA Approves Nirogacestat for Adult Patients with Progressing Desmoid Tumors

By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY


On the date of approval, the U.S. Food and Drug Administration approved Nirogacestat (Ogsiveo) for adult patients with progressing desmoid tumors who require systemic treatment. This marks the first approved treatment for desmoid tumors.


Study ID number: NCT03785964


Approval was based on the phase 3 DeFi trial (NCT03785964), a multicenter, double-blind, placebo-controlled study that included 142 patients with desmoid tumors that had progressed within 12 months of screening. Nirogacestat was given orally at a dose of 150 mg twice daily until disease progression or intolerable toxicity. The median treatment duration was 20.6 months.


Progression free survival (PFS) was the major efficacy outcome measure while objective response rate (ORR) was the additional efficacy outcome measure. There was a 71% reduction in the risk of disease progression or death vs placebo in this population. The median PFS in the investigative arm was not reached vs 15.1 months (95% CI, 8.4-NR) in the placebo arm (HR, 0.29; 95% CI, 0.15-0.55; P < .0001). An ORR of 41% was achieved with nirogacestat compared to 8% with placebo. Nirogacestat significantly reduced disease progression or death and improved patient-reported worst pain. An exploratory analysis of PFS based on radiographic progression only revealed a hazard ratio of 0.31 (95% CI: 0.16, 0.62).


Nirogacestat represents an important therapeutic advance for patients with desmoid tumors. It demonstrated both meaningful antitumor activity and a significant improvement in desmoid tumor symptoms.


The most common adverse effects included diarrhea, nausea, stomatitis, abdominal pain, ovarian toxicity, rash, alopecia, fatigue, headache, cough, dyspnea, and upper respiratory tract infection. Laboratory abnormalities that worsened from baseline in at least 15% of patients included decreased phosphate and potassium, and increased urine glucose, urine protein, AST, and ALT.


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