Onapristone Trial Evaluates Response Rates in Progesterone Receptor Positive Recurrent Granulosa Cell Ovarian Cancer

An open, multicenter phase II trial (NCT03909152) of extend-release (ER) onapristone (Apristor) in patients with progesterone receptor—positive (PR+) recurrent granulosa cell ovarian cancer, low-grade serous ovarian/primary peritoneal cancer, or endometroid endometrial cancer will demonstrate if the investigational drug will shrink or stop the cancer.

In the basket study involving onapristone ER, 84 women will receive 50 mg of the drug by mouth twice daily for a 28-day cycle. The cycles will continue until disease progression, unacceptable toxicity, or if the patient decides to withdraw consent. The first patients being enrolled will have low-grade serous ovarian cancer.

The primary end point is response rate within 36 weeks of starting on onapristone ER, which will be determined by RECIST 1.1 response. All the patients will be treated at 1 of the Memorial Sloan Kettering locations.

Newly diagnosed and relapsed/refractory patients are eligible for the trial. Additionally, eligible patients will have PR+ recurrent granulosa cell ovarian cancer, low-grade serous ovarian/primary peritoneal cancer, or endometroid endometrial cancer who have been treated with 1 prior chemotherapy regimen at least 3 weeks previously.

In a previous clinical trial involving patients with metastatic breast cancer, onapristone ER monotherapy had an overall response rate (ORR) of 56%, a 17.5-month duration of response, and median progression-free survival of 14 months.¹Another trial of onapristone ER had a 25% ORR and 50% clinical benefit rate (CBR) in patients with tamoxifen-resistant breast cancer.²In the most recent phase I trial, heavily pre-treated patients had a CBR of 17%.³

The 3 selected gynecologic cancers are driven by progesterone, which is the hormone responsible for regulating the menstrual cycle. This study will assess if onapristone ER, a progesterone antagonist, can shrink the cancer or stop cancer cells from growing and spreading.⁴

The manufacturer, Context Therapeutics, is also planning a prospective phase II multicenter trial of fulvestrant (Faslodex) and onapristone compared with fulvestrant alone in patients with estrogen receptor—positive, progesterone receptor–positive, HER2-negative metastatic breast cancer after they have progressed on a combination therapy of a CDK4/6 inhibitor and an aromatase inhibitor.

References

1. Robertson JF, Willsher PC, Winterbottom L, Blamey RW, Thorpe S. Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer.Eur J Cancer.1999;35(2):214-218. doi: 10.1016/s0959-8049(98)00388-8.
2. Jonat W, Giurescu M, Robertson JFR. The clinical efficacy of progesterone antagonists in breast cancer.End Ther Breast Can. 2002;(1):117-124.
3. Cottu PH, Bonneterre J, Varga A, et al. Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic progesterone receptor-expressing cancers.PLoS ONE.2018;13(10):e0204973. doi: 10.1371/journal.pone.0204973.
4. A study of extended-release onapristone in gynecologic cancers that respond to progesterone. Memorial Sloan Kettering Cancer Center website. https://www.mskcc.org/cancer-care/clinical-trials/19-061. Published January 10, 2020. Accessed January 28, 2020.