Nirogacestat Approved for Desmoid Tumors

Intraabdominal desmoid tumor.

The FDA has granted approval to nirogacestat (Ogsiveo™, SpringWorks Therapeutics, Inc.) for adult patients with progressing desmoid tumors who require systemic treatment. This is the first approval for nirogacestat and the first approved treatment for desmoid tumors.  

Why it matters: “Management of desmoid tumors is challenging because of their variable presentation and unpredictable disease course, with spontaneous regression seen in up to 20% to 30% of patients over time,” wrote Mrinal Gounder, MD, a Sarcoma Oncologist at Memorial Sloan Kettering Cancer Center, and colleagues, in their published results of the DeFi trial (NCT03785964), on which approval was based. “Currently, no therapies are approved, and existing management guidelines vary depending on tumor location, symptoms, and disease progression.”

What they studied: Efficacy was studied in the phase 3, international, multicenter, double-blind, placebo-controlled trial, in which 142 patients with progressing desmoid tumors not amenable to surgery were enrolled. Eligibility criteria required that the patient’s desmoid tumor progressed within 12 months of screening. Patients were randomized 1:1 to receive either 150 mg of nirogacestat or placebo orally, twice daily. Treatment continued until unacceptable toxicity or disease progression. The primary end point measured was progression-free survival based on RECIST v1.1 as assessed by blinded independent central review or by the investigator and adjudicated by independent review. The key secondary end point was objective response rate.

What they found: For patients being treated with nirogacestat, median progression-free survival was not reached compared with a median of 15.1 months for those receiving placebo. Objective response rate was seen in the nirogacestat arm at 41% compared with the placebo arm at 8%.

Adverse events: The most common adverse events experienced by those being treated with nirogacestat were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.

What to know: Efficacy results were supported by change from baseline in patient-reported worst pain favoring the nirogacestat arm.

Conclusion: “In this trial involving patients with progressing desmoid tumors, nirogacestat showed significant benefits with respect to progression-free survival, objective response, pain, disease-specific symptom burden, physical functioning, role functioning, and health-related quality of life,” concluded Dr. Gounder and colleagues.

Instructions: The recommended dosage is 150 mg, administered as three 50 mg tablets of nirogacestat orally, twice daily, with or without food, until disease progression or unacceptable toxicity.

For More Information

Ogsiveo™ (nirogacestat) prescribing information will be made available here.

Gounder M, Ratan R, Alcindor T, et al (2023). Nirogacestat, a γ-secretase inhibitor for desmoid tumors. N Engl J Med, 388(10):898-912. DOI:10.1056/NEJMoa2210140 (2023). Nirogacestat for adults with desmoid tumor/aggressive fibromatosis (DT/AF) (DeFi). NLM identifier: NCT03785964.

US Food and Drug Administration (2023). FDA approves nirogacestat for desmoid tumors. Available at:

Image credit: Sarahkayb. Licensed under CC BY-SA 4.0

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