Trial in Progress: A Phase Two Trial of Nirogacestat, a Gamma-Secretase Inhibitor, in Patients with Recurrent Ovarian Granulosa Cell Tumors (NCT05348356) (1284)

Ovarian granulosa cell tumors (OvGCT) represent 5–7% of all ovarian cancers and account for 70% of ovarian sex cord-stromal tumors. Surgery is the initial treatment, with postoperative therapy considered for patients with more advanced diseases. In relapsed patients, various chemotherapeutic regimens have shown only modest activity. Notch signaling, the FOXL2 C134W mutation, and dysregulation of the PI3K/AKT pathway are integral to the molecular pathogenesis of OvGCT. Nirogacestat (PF-03084014) is a potent, selective, reversible, noncompetitive inhibitor of γ-secretase, an enzyme that plays a pivotal role in Notch signaling.