FDA approves nirogacestat for desmoid tumors
Regulatory approval: On Nov 27, 2023, the FDA approved nirogacestat (OGSIVEO; SpringWorks Therapeutics) for adult patients with progressing desmoid tumors who require systemic treatment. The decision was supported by the phase 3 DeFi trial (NCT03785964), which reported improved progression-free survival versus placebo (HR 0.29; p<0.001) and higher objective response rate (41% vs 8%; p<0.001). This is described as the first approved treatment for desmoid tumors.
FDA approval: nirogacestat for desmoid tumors (Nov 27, 2023)
Type: Regulatory approval
On November 27, 2023, the FDA approved nirogacestat (OGSIVEO; SpringWorks Therapeutics, Inc.) for adult patients with progressing desmoid tumors who require systemic treatment. The FDA stated this is the first approved treatment for desmoid tumors.
Key efficacy evidence (DeFi; NCT03785964)
Efficacy was evaluated in DeFi, an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial in 142 patients with progressing desmoid tumors not amenable to surgery (progression within 12 months of screening). Patients received nirogacestat 150 mg orally twice daily or placebo until disease progression or unacceptable toxicity.
- Progression-free survival (PFS): median PFS not reached with nirogacestat vs 15.1 months with placebo; HR 0.29 (95% CI 0.15–0.55), p<0.001. An exploratory PFS analysis using radiographic progression only reported HR 0.31 (95% CI 0.16–0.62).
- Objective response rate (ORR): 41% (95% CI 29.8–53.8) vs 8% (95% CI 3.1–17.3); p<0.001.
- Patient-reported worst pain change from baseline favored nirogacestat.
Safety and dosing (per FDA summary)
Common adverse reactions included diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea. Recommended dose: 150 mg orally twice daily (three 50 mg tablets per dose), with or without food, until progression or unacceptable toxicity.