Basket Study of Apristor in Women With Progesterone Receptor Positive (PR+) Recurrent Granulosa Cell Tumor, Low Grade Serous Ovarian Cancer, or Endometrioid Endometrial Cancer

Trial Status:
Enrollment in this Phase 2 study is open.

Program (Target):
Apristor (onapristone extended release) is a potent and specific antagonist of the progesterone receptor that is orally administered. Currently, there are no approved therapies that selectively target PR+ cancers. Preliminary preclinical and clinical data suggest that Apristor has anticancer activity by inhibiting the binding of progesterone receptor to chromatin, downregulating cancer stem cell mobilization, and blocking immune evasion.

Apristor has not been approved for marketing by any regulatory authority.

Disease Indication:
Low grade serous ovarian cancer, granulosa cell tumor of the ovary, and endometrioid endometrial cancer.

Clinical Trial Description:
A multicenter, open-label, Simon 2-stage adaptive Phase 2 “Basket” trial (NCT03909152) to evaluate the efficacy and safety of the anticancer agent Apristor in advanced gynecological tumors that are progesterone receptor positive (PR+). This Basket trial will include patients who have different PR+ solid tumors in advanced stages, including low grade serous ovarian, granulosa cell, and endometrioid endometrial cancer who have received prior chemotherapy treatment. The progesterone receptor antagonist Apristor will be tested in up to 84 cancer patients. The primary endpoint will assess the overall response rate (ORR), which is the proportion of patients that have either a complete or partial response, obtained with Apristor in each of these tumors. The secondary objectives of the study will include endpoints to better characterize the activity of Apristor, such as duration of response, clinical benefit, and progression-free survival (PFS). In addition, this study will evaluate the safety and pharmacological profile of Apristor in these patients, as well as biomarker analyses to explore predictive factors of drug response. Preliminary trial results are expected in early 2020.

Trial Sites:

City State Institution
Basking Ridge New Jersey Memorial Sloan Kettering Basking Ridge
Montvale New Jersey Memorial Sloan Kettering Bergen
Middletown New Jersey Memorial Sloan Kettering Monmouth
Commack New York Memorial Sloan Kettering Commack
New York New York Memorial Sloan Kettering Cancer Center
Rockville Centre New York Memorial Sloan Kettering Rockville Centre
Harrison New York Memorial Sloan Kettering Westchester

Huang, Y, et al. (2018) Inhibiting Nuclear Phospho-Progesterone Receptor Enhances Antitumor Activity of Onapristone in Uterine Cancer. Mol Cancer Ther. 2018 Feb;17(2):464-473. doi: 10.1158/1535-7163.

Cottu PH, et al. (2018) Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers. PLoS ONE 13(10): e0204973.