The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:
On November 27, 2023, the Food and Drug Administration approved nirogacestat (OGSIVEO, SpringWorks Therapeutics, Inc.) for adult patients with progressing desmoid tumors who require systemic treatment. This is the first approved treatment for desmoid tumors.
Full prescribing information for OGSIVEO will be posted here.
Efficacy was evaluated in DeFi (NCT03785964), an international, multicenter, randomized (1:1), double-blind, placebo-controlled trial in 142 patients with progressing desmoid tumors not amenable to surgery. Patients were eligible if the desmoid tumor had progressed within 12 months of screening. Patients were randomized to receive 150 mg nirogacestat or placebo orally twice daily until disease progression or unacceptable toxicity.
The major efficacy outcome measure was progression-free survival (PFS) based on RECIST v1.1 as assessed by blinded independent central review or on clinical progression by the investigator (and adjudicated by independent review). Median PFS was not reached (NR) in the nirogacestat arm (95% CI: NR, NR) and 15.1 months (95% CI: 8.4, NR) in the placebo arm (hazard ratio [HR] 0.29 [95% CI: 0.15, 0.55]; p-value=<0.001). An exploratory analysis of PFS based on only radiographic progression demonstrated a hazard ratio of 0.31 (95% CI: 0.16, 0.62).
Objective response rate (ORR) was an additional efficacy outcome measure. ORR was 41% (95% CI: 29.8, 53.8) in the nirogacestat arm and 8% (95% CI: 3.1, 17.3) for those receiving placebo (p-value=<0.001). Additionally, efficacy results were supported by change from baseline in patient-reported worst pain favoring the nirogacestat arm.
The most common adverse reactions were diarrhea, ovarian toxicity, rash, nausea, fatigue, stomatitis, headache, abdominal pain, cough, alopecia, upper respiratory tract infection, and dyspnea.
The recommended nirogacestat dose is 150 mg administered orally twice daily with or without food until disease progression or unacceptable toxicity. Each 150 mg dose consists of three 50 mg tablets.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review, breakthrough designation, fast track designation, and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.
