Mifepristone-eribulin combination clinically active in triple-negative breast cancer patients

Early results published in 2015 American Society of Clinical Oncology (ASCO) Annual Meeting Program

Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of cortisol, today announced results of a multi-center Phase 1/2 dose-escalation study of mifepristone and chemotherapy drug eribulin (Halaven^®) that show it is well tolerated and clinically active in patients with triple-negative breast cancer. These results were published in the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting Program (abstract e12070), which was released today.

“Triple-negative breast cancers are among the most aggressive and difficult to treat of all the breast cancer types. We are encouraged by the results we have seen using mifepristone to enhance the efficacy of chemotherapy in this patient population,” said Rita Nanda, MD, principal investigator and Associate Director, Breast Medical Oncology, University of Chicago Medicine. “Cancer patients abundantly produce the stress hormone cortisol, which can help tumor cells escape chemotherapy effectiveness when cortisol binds to the cells’ glucocorticoid receptors (GR). Because mifepristone also binds with tumor GR, we are postulating that mifepristone will lessen the cortisol activity in tumor cells and make chemotherapy more effective. Patients with triple-negative breast cancer need better treatments and we are hopeful that mifepristone when combined with chemotherapy, will benefit them.”

Researchers enrolled 13 metastatic breast cancer patients for the first phase of the study to determine the maximum tolerated dose of the mifepristone-eribulin combination. The results showed that the combination regimen was well-tolerated with evidence of clinical activity for patients with triple-negative breast cancer (TNBC). The recommended Phase 1/2 dose of 300 mg of mifepristone daily with 1.1./mg/m2 of eribulin showed no evidence of a drug-drug interaction and will be used in the next phase of the study. An additional 20 patients with GR-positive metastatic TNBC will be enrolled into the study’s efficacy phase.

Although the dose-selection phase of the study was designed to assess only safety and tolerability, some preliminary efficacy data was produced. Patients with metastatic breast cancer (five with triple-negative breast cancer) were treated with mifepristone and eribulin at three different dose levels. The study consisted of seven patients with GR-positive tumors, three patients with GR-negative tumors and three patients with unknown GR status. Two partial responses have been observed, both in patients with GR-positive cancer. Of the 13 total patients in the study, four experienced neutropenia, leading to delay of eribulin. Grade 3/4 neutropenia was observed in nine patients but was easily managed. Neuropathy was observed in two patients. No other significant toxicity was noted in the study.

“Glucocorticoid receptor antagonists, such as mifepristone, the active ingredient in our product Korlym^®, have shown great promise in treating a variety of severe diseases, including GR-positive triple-negative breast cancer,” said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. “If our Phase 1/2 demonstrates efficacy, we plan to begin a Phase 3 study in early 2016. We are also developing compounds from our portfolio of next-generation selective GR antagonists. We hope to advance our lead compound, CORT125134, to a Phase 2 study for the treatment of a second oncology indication early next year.”

The University of Chicago and participating sites from U.S. Oncology Research will continue to enroll patients into the second phase of the study.