Key Inclusion Criteria:
* Participant is aged ≥18 at the time of signing the informed consent.
* Participant has histologically confirmed DT (by local pathologist prior to informed consent) that has progressed by ≥20% as measured by RECIST v1.1 within 12 months of the screening visit scan.
* Participant has:
1. Treatment-naive, measurably progressing DT that is deemed not amenable to surgery without the risk of significant morbidity; OR
2. Recurrent, measurably progressing DT following at least 1 line of therapy; OR
3. Refractory, measurably progressing DT following at least 1 line of therapy.
* Participant agreed to provide archival or new tumor tissue for re-confirmation of disease.
* Participant has a DT tumor where continued PD will not result in immediate significant risk to the participant.
* Participants who are receiving chronic NSAIDs as treatment for conditions other than DT must be receiving them prior to documented DT progressive disease (inclusion criterion 2) and on a stable dose for at least 28 days prior to the first dose of study treatment.
* Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
* Participant has adequate organ and bone marrow function
Key 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.
* 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 severe 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 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 electronic patient-reported outcomes)
