Nirogacestat for Adults With Desmoid Tumor/Aggressive Fibromatosis (DT/AF) (DeFi)

Why are we doing this research?

The primary goal is to evaluate nirogacestat in the treatment of desmoid tumor/aggressive fibromatosis (DT/AF). Half of the participants will receive nirogacestat while the other half will receive placebo.

NIR-DT-301: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Nirogacestat Versus Placebo in Adult Patients with Progressing Desmoid Tumors/Aggressive Fibromatosis (DT/AF)

Who can participate?

Inclusion Criteria:

  • Participant has DT/AF that has progressed by ≥20% as measured by RECIST Version 1.1 Criteria within the 12-month period prior to first dose of study treatment.
  • Participant has newly diagnosed, measurably progressing DT/AF that is not amenable to surgical resection or radiation therapy; OR recurrent, progressing DT/AF following CR to initial therapy; OR preexisting DT/AF and has previously received therapy and the residual tumor has progressed.
  • Participant agrees to provide archival or new tumor tissue for confirmation of disease.
  • If participant was previously treated with an investigational therapy for treatment of DT/AF, participant must have completed prior therapy at least 28 days prior to signing informed consent.
  • Participants who are receiving nonsteroidal anti-inflammatory drugs (NSAIDs) as treatment for conditions other than DT/AF.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening.
  • Participant has adequate organ and bone marrow function.

Exclusion Criteria:

  • Participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat.
  • Participant has experienced any of the following within 6 months of signing informed consent: clinically significant cardiac disease (New York Heart Association Class III or IV), myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
  • Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
  • Current or chronic history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones).
  • Participant previously received or is currently receiving therapy with GS inhibitors or anti-Notch antibody therapy.
  • Participant is currently using or anticipates using a tyrosine kinase inhibitor within 28 days of study treatment.
  • Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 3A4 (CYP3A4) inhibitors or strong inducers within 14 days prior to the first dose of study treatment.
  • Participant is currently using or anticipates using chronic daily NSAIDs for treatment of DT/AF within 28 days of study treatment.
  • Participant is unable to tolerate MRI or for whom MRI is contraindicated.
  • Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year of study start.


  • 18 years or older


  • Adult - Brain and Spinal Tumor Neurofibromatosis Sarcoma MPNST Relapse - Refractory
  • Adult - Brain and Spinal Tumor Neurofibromatosis Sarcoma MPNST New Diagnosis


Cincinnati Children’s Hospital Medical Center
Division of Hematology/Oncology
3333 Burnet Ave., Cincinnati, OH 45229-3039
Phone: 513-636-2799