Background: ONA-XR is a type I full progesterone antagonist that inhibits progesterone-mediated PR activation and stabilizes PR association with corepressors. GCT (98% of cases PR+), LGSOC (58% of cases PR+) and EEC (67% of cases PR+) are hormonally driven cancers that generally have poor responses to chemotherapy. Methods: This is an open-label, single-institution basket study of ONA-XR in patients with PR+ recurrent GCT (cohort 1), LGSOC (cohort 2), or EEC (cohort 3) (NCT03909152). Eligible patients required receipt of >1 prior line of chemotherapy, measurable disease by RECIST 1.1, and tumor tissue collected ≤3 years prior to enrollment with PR ≥ 1% by IHC. Patients received ONA-XR 50 mg PO BID until progression or intolerable toxicity. The study was designed as 3 parallel Simon 2-Stage studies. The primary objective was to evaluate efficacy, determined by RECIST 1.1, with at least 1/14 (cohort 1), 2/16 (cohort 2) or 4/19 (cohort 3) responses needed during stage 1 for advancement to stage 2. Secondary objectives included safety and tolerability, clinical benefit rate (CBR; stable disease lasting ≥ 16 weeks), and progression-free survival (PFS) as estimated by Kaplan Meier method. Results: The study enrolled patients to cohorts 1-3 from 5/2019 to 5/2020. Cohort 2 (LGSOC) enrolled 5 patients and cohort 3 (EEC) enrolled 1, both closed early due to slow accrual. Cohort 1 (GCT) enrolled 14 patients and completed Stage 1 accrual. There were no responses by RECIST 1.1 criteria observed in cohorts 1-3. In cohort 2 (LGSOC), 4/5 enrolled patients were evaluable, the median PFS was 4.4 months (1.8-NE) and CBR was 50% (6.8-93.2%). All 14 patients enrolled to cohort 1 (GCT) were evaluable with a median PFS of 3.5 months (1.6-8.8%), 6-month PFS rate of 30.1 % (8.4-56%), and 12-month PFS rate of 20.1% (3.5-46.4%). The CBR was 35.7% (12.8-64.9%). Two patients with GCT remain on active treatment for > 18 months. Grade 3 adverse events occurred in 5 patients: abdominal pain (2), small bowel obstruction (1), syncope (1), thromboembolism (1), urinary tract infection (1), and febrile neutropenia (1). Grade 3 laboratory toxicity occurred in 5 patients: anemia (2), neutropenia (1) and lymphopenia (2). Conclusions: ONA-XR was well tolerated and exhibited a 12-month PFS rate of 20.1% and a CBR of 35.7% in patients with GCT. No objective responses were observed. Cohorts 1-3 have closed to accrual, with 2 patients continuing active treatment for >18 months. Cohort 4, which combines ONA-XR with anastrozole, is currently enrolling patients with GCT. Clinical trial information: NCT03909152.

NR: Not Reached, (2-sided 95% CI)