A First-in-Class Progesterone Receptor Antagonist
ABOUT HORMONE DRIVEN CANCERS
Over 100,000 patients with metastatic breast, ovarian, prostate, or uterine cancers die per year in the United States. For many of these patients, continuous progesterone and estrogen signaling drives disease progression. Currently, only medicines that block estrogen are approved, meaning that progesterone signaling continues in those patients receiving anti-estrogen therapy.
Apristor (onapristone xr) is an investigational medicine that prevents progesterone signaling by blocking the interaction between progesterone and its binding partner, progesterone receptor. Apristor is the only known full PR antagonist.
ROLE OF PR IN CANCER
Under normal conditions, progesterone is primarily responsible for the development of sex organs and for regulating the menstrual cycle. Cancer cells hijack progesterone to stimulate cancer cell proliferation, metastases, regeneration, and immune evasion.
LEAD INDICATION - Second Line Metastatic Breast Cancer (2L mBCa)
An estimated 40,000 patients in the United States currently have 2L mBCa. Most of these patients will have progressed on prior anti-Cdk4/6 plus antiestrogen combination therapy. Upon progression, patients exhibit a complex resistance profile that renders the current second line standard of care, Faslodex (fulvestrant), largely ineffective.
Progesterone receptor has emerged as a central resistance mechanism for up to 70% of these second line patients.
Apristor has been evaluated in clinical trials as a monotherapy in metastatic breast, ovarian, and endometrial cancer. Context seeks to expand upon these preliminary findings via Context-sponsored or Investigator Initiated Phase 2 trials.
RESOURCES & PUBLICATIONS
- 1L mBCa Phase 2 Trial: Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer
- 2L mBCa Phase 2 Trial: Onapristone in tamoxifen-resistant disease
- 3L+ PR+ Cancers: Phase I study of onapristone, a type I antiprogestin, in female patients with previously treated recurrent or metastatic PR-expressing cancers
- MOA Review: Progesterone action in breast, uterine, and ovarian cancers
- Gyn Cancer Review: The Role of Hormonal Therapy in Gynecological Cancers
- Uterine Cancer: Inhibiting Nuclear PR Enhances Antitumor Activity of Onapristone in Uterine Cancer
- Cell Cycle: Cyclin D1 Enhances the Response to Progesterone By Regulating Progesterone Receptor Expression
- Immune Regulation: Interferon-StimulatedGenesAre Transcriptionally Repressed by PR in Breast Cancer
- DNA Repair: BRCA1 Counteracts Progesterone Action