FDA D.I.S.C.O. Burst Edition: FDA approval of OGSIVEO (nirogacestat) for adult patients with progressing desmoid tumors who require systemic treatment
Regulatory approval: On Nov 27, 2023, the FDA approved nirogacestat (OGSIVEO) for adult patients with progressing desmoid tumors who require systemic treatment, described as the first approved treatment for desmoid tumors. Approval was supported by the randomized, double-blind, placebo-controlled DeFi trial (n=142) in patients with progressing desmoid tumors not amenable to surgery. Median PFS was not reached with nirogacestat vs 15.1 months with placebo; ORR was 41% vs 8%.
FDA approval (Nov 27, 2023): nirogacestat (OGSIVEO) for progressing desmoid tumors
Type: Regulatory approval (FDA)
On November 27, 2023, the FDA approved nirogacestat (OGSIVEO) for adult patients with progressing desmoid tumors who require systemic treatment. FDA characterized this as the first approved treatment for desmoid tumors.
Supporting evidence: DeFi trial
Efficacy was evaluated in DeFi, an international, multicenter, randomized, double-blind, placebo-controlled trial enrolling 142 patients with progressing desmoid tumors not amenable to surgery. Eligibility required tumor progression within 12 months of screening. Patients were randomized to nirogacestat 150 mg orally twice daily or placebo until disease progression or unacceptable toxicity.
Primary efficacy outcome: progression-free survival (PFS) per RECIST v1.1 by blinded independent central review or clinical progression adjudicated by independent review. Median PFS was not reached with nirogacestat vs 15.1 months with placebo. An exploratory PFS analysis based only on radiographic progression showed HR 0.31.
Additional outcome: objective response rate (ORR) was 41% with nirogacestat vs 8% with placebo. Results were also supported by change from baseline in patient-reported worst pain favoring nirogacestat.
Safety
Most common adverse reactions included diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
The review used FDA’s Real-Time Oncology Review pilot program and an Assessment Aid submission.