This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.
Participant is female, postpubertal aged ≥18 and ≤40 years of age at the time of signing the informed consent and premenopausal at baseline. Premenopausal is defined as meeting all of the following: Estradiol >30 pg/mL. Follicle-stimulating hormone (FSH) <40 IU/L. Regular menses (e.g., menstrual cycle length of 21 to 35 days) for at least 3 menstrual cycles prior to signing informed consent
Participant uses 1 highly effective non-hormonal contraceptive method, has a negative pregnancy test prior to first dose of study treatment), is not breastfeeding, agrees to not harvest or donate eggs for at least 90 days prior to and during the study
Participant has histologically confirmed DT/AF with symptomatic or progressive disease requiring systemic treatment
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
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
Single group
Nirogacestat
DrugNirogacestat oral tablet
Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)
Ovarian function recovery is defined as achieving the resumption of ≥2 consecutive menstrual periods and an FSH level \<30 mIU/mL with concomitant estradiol \<80 pg/mL OR resumption of ≥2 consecutive menstrual periods and AMH level within normal range adjusted for age and pretreatment baseline OR a positive serum β-HCG pregnancy test.
Incidence of OT TEAEs
OT is any new onset amenorrhea lasting ≥3 consecutive menstrual periods, FSH level ≥30 mIU/mL and a negative β-HCG pregnancy test.
Time to ovarian function recovery in participants with a TEAE of OT
Time to ovarian function recovery is evaluated in participants who had a TEAE of OT and is defined as the time it takes to resolve.
The incidence of adverse events (AEs) according to toxicities graded by National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) Version 5
Objective Response Rate (ORR)
Proportion of participants with Complete Response (CR) and Partial Response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Duration of Response (DoR) for participants whose best response is CR or PR
DoR is defined as the duration from the time of first assessment of CR or PR response (per RECIST v1.1) to the first date of disease progression or death (whichever comes first).
Disease Control Rate (DCR) for participants whose best response is CR, PR or Stable Disease (SD)
DCR is defined as the proportion of participants who have a best response of CR, PR, or SD.
Duration of Disease Control (DoDC) for participants whose best response is CR, PR or SD
DoDC is defined as the duration from the start of study treatment until first date of disease progression or death (whichever comes first).
Click on the lead sponsor to view all of their trials.
