Nirogacestat in Premenopausal Females With Desmoid Tumor/Aggressive Fibromatosis (DT/AF)

Exclusion Criteria12

• 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.
• Participant has had lymphoma, leukemia, or any malignancy within the past 5 years at the time of informed consent, except for any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast), with no evidence of metastatic disease for 3 years at the time of informed consent.
• Participant has known hepatic impairment
• Participant previously received or is currently receiving gamma secretase inhibitors or anti-Notch antibody therapy
• Participant is currently using any treatment for DT/AF including tyrosine kinase inhibitors (TKIs) or any investigational treatment 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment
• Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 (CYP) 3A4 inhibitors, or strong CYP3A inducers within 14 days prior to the first dose of study treatment.
• Participant has a history of polycystic ovary syndrome, hypothalamic amenorrhea, severe endometriosis involving ovaries, family history of primary ovarian insufficiency, any chromosomal abnormality, mutation, gene variant or medical condition associated with early/premature menopause, including a history of OT while on a TKI
• Participant is currently using or has used hormonal contraception or ovarian suppression within 90 days prior to first dose of study treatment
• Participant has a history of heavy tobacco smoking (≥20 pack years) or is a current smoker (>1 pack per day)
• Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year of signing informed consent.
• Participant is unable to comply with study related procedures (including, but not limited to, the completion of a menstrual diary and electronic patient-reported outcomes and ability to return to clinic for hormone level blood draws timed to the menstrual cycle (days 1-5)