SpringWorks Therapeutics, Inc. announced that the first patient has been dosed in a Phase 2 trial evaluating nirogacestat, SpringWorks' investigational gamma secretase inhibitor, as a monotherapy in patients with recurrent ovarian granulosa cell tumors. Ovarian granulosa cell tumors account for approximately 5% of all ovarian cancers and are the most common subtype of ovarian sex cord tumors, representing 70% of all cases. Nearly all ovarian granulosa cell tumors harbor a mutation in the FOXL2 gene and preclinical studies have demonstrated that ovarian granulosa cell tumor cell lines are susceptible to gamma secretase inhibition.

The Phase 2 trial (NCT05348356) is a multi-center, single-arm, open-label study evaluating the efficacy, tolerability, safety, and pharmacokinetics of nirogacestat in patients with recurrent ovarian granulosa cell tumors. The study will enroll approximately 40 patients who will receive 150mg of nirogacestat twice daily. Eligible patients will have recurrent ovarian granulosa cell tumors and will have received one or more prior lines of systemic therapy.

The primary endpoint of the trial is objective response rate as measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1). Secondary endpoints include progression-free survival, overall survival, duration of response, safety and tolerability, and quality of life assessments.