On June 2, 2016 Corcept Therapeutics Incorporated (NASDAQ: CORT), a pharmaceutical company engaged in the discovery, development and commercialization of drugs that treat severe metabolic, psychiatric and oncologic disorders by modulating the effects of the stress hormone cortisol, released preliminary efficacy data from its Phase 1/2 trial of mifepristone to treat patients with metastatic triple-negative breast cancer (TNBC) (Press release, Corcept Therapeutics, JUN 2, 2016, http://www.corcept.com/news_events/view/pr_1464901246 [SID:1234512972]). The company also provided an update of developments in other clinical trials of cortisol modulators, including mifepristone, to treat a variety of solid-tumor cancers. Schedule your 30 min Free 1stOncology Demo! "Preliminary data from our Phase 1/2 trial in patients with TNBC support our hypothesis that cortisol modulators such as mifepristone augment standard chemotherapy in difficult to treat solid-tumor cancers," said Joseph K. Belanoff, MD, Corcept’s Chief Executive Officer. "We look forward to the trial’s final results, which will guide us as we advance our oncology programs."
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"It’s exciting to see the study of cortisol modulation as a treatment for GR-positive solid-tumor cancers advance so broadly," said Robert S. Fishman, MD, Corcept’s Chief Medical Officer. "In addition to our trial combining mifepristone and Halaven, we have begun dosing patients in a Phase 1/2 trial combining our proprietary cortisol modulator, CORT125134, with Abraxane. Our colleagues at the University of Chicago are also taking important steps to explore cortisol modulation’s potential in oncology. They have begun enrolling patients in a Phase 2 trial of mifepristone plus Xtandi to treat CRPC. In the coming months, they plan to start a controlled Phase 2 study, with support from Celgene and Corcept, of mifepristone in combination with Abraxane to treat patients with TNBC."
Preliminary Results in Corcept’s Phase 1/2 Trial of Mifepristone to Treat TNBC
This open-label trial is investigating whether the addition of mifepristone enhances the effect of Halaven in patients with TNBC whose tumors express the glucocorticoid receptor (GR), one of the receptors to which mifepristone binds.
The trial has enrolled 21 patients with GR-positive tumors and two with tumors whose GR status is not currently known. As determined using the Response Evaluation Criteria in Solid Tumors (RECIST), preliminary efficacy results in this group were as follows: Three patients exhibited a partial response, defined as a 30 percent or greater reduction in tumor size, eight had stable disease and 11 had progressive disease. One patient is too early in treatment to be assessed (see Figure 1).
"These preliminary data are encouraging," said Dr. Fishman. "For example, five patients achieved progression-free survival (PFS) longer than the upper bound for PFS in TNBC patients receiving Halaven monotherapy in a comparable population (Aogi et al., Annals of Oncology 23: 1441-1448, 2012). We expect our analysis of the complete, final data will tell us more."
The combination of mifepristone and Halaven has been well-tolerated. Neutropenia has been manageable with the administration of growth factor. Other adverse events have been mainly of mild or moderate severity, with the most common being fatigue, nausea, hypokalemia, hair loss and neuropathy.
Final results are expected in mid-2016.
Corcept’s Phase 1/2 Trial of CORT125134 to Treat Solid-Tumor Cancers
Corcept has begun dosing patients in a trial of its proprietary, selective cortisol modulator, CORT125134, together with Abraxane to treat solid-tumor cancers (clinicaltrials.gov identifier NCT02762981). The trial’s first phase will identify a recommended dose of Abraxane and CORT125134. The second phase will test the combination’s efficacy against a range of tumor types in one or more 20-patient cohorts. Possible target indications include TNBC, CRPC, ovarian cancer, pancreatic cancer and sarcoma. Other cohorts may be enrolled to study CORT125134 with different companion agents, including PD-1 inhibitors. In animal models, the addition of CORT125134 to PD-1 monotherapy significantly slowed tumor progression relative to PD-1 monotherapy. (For more information, see the company’s press release of April 28, 2016 at corcept.com.)
Initial results are expected in 2017.
University of Chicago Two Phase 2 Trials of Mifepristone to Treat CRPC and TNBC
Researchers at the University of Chicago have begun enrolling patients in the Phase 2 portion of their trial of mifepristone combined with Xtandi to treat patients with metastatic CRPC (clinicaltrials.gov identifier NCT02012296). The University of Chicago investigators are also planning to conduct a placebo-controlled, double-blind, Phase 2 trial of mifepristone combined with Abraxane to treat patients with advanced, GR-positive TNBC (clinicaltrials.gov identifier NCT02788981).
Celgene is providing support for the Abraxane/mifepristone trial. The Department of Defense and the Prostate Cancer/Movember Foundation are providing support for the CRPC trial.
Corcept is providing mifepristone to both the TNBC and CRPC trials.
Corcept has licensed patents from the University of Chicago covering the use of cortisol modulators in combination with anti-cancer agents to treat TNBC and CRPC.
About TNBC
TNBC is a form of breast cancer in which the three receptors that fuel most breast cancer growth – estrogen, progesterone and HER-2 – are not present. Because the tumor cells lack these receptors, treatments that target estrogen, progesterone and HER-2 are ineffective. Approximately 40,000 women are diagnosed with triple-negative breast cancer each year. It is estimated that more than 75 percent of these women’s tumor cells express GR. There is no FDA-approved treatment and neither a targeted treatment nor an approved standard chemotherapy regimen for relapsed triple-negative breast cancer patients exists. Corcept has licensed patents from the University of Chicago covering the use of GR antagonists in combination with chemotherapy to treat TNBC and castration-resistant prostate cancer.
About CRPC
Castration-resistant prostate cancer (CRPC) is a form of the disease that progresses despite androgen receptor blockade. There are approximately 130,000 patients with metastatic CRPC in the United States. The prognosis for patients with metastatic disease is poor.
About Mifepristone
Mifepristone is the active ingredient in Corcept’s product, Korlym 300mg tablets, which the FDA has approved for the once-daily oral treatment of hyperglycemia secondary to endogenous Cushing’s syndrome in adult patients with glucose intolerance or diabetes mellitus type 2 who have failed surgery or are not candidates for surgery. Korlym (mifepristone) ameliorates the symptoms of Cushing’s syndrome by modulating the activity of cortisol at GR, one of the two receptors to which cortisol binds. Korlym was the first FDA-approved treatment for that illness and the FDA has designated it as an Orphan Drug for that indication.
About CORT125134
CORT125134 is the lead compound in Corcept’s portfolio of selective cortisol modulators. It is a non-steroidal competitive antagonist of GR that does not bind to the body’s other hormone receptors, including the progesterone receptor. It is the affinity of Korlym for the progesterone receptor that results in termination of pregnancy and can cause endometrial thickening and irregular vaginal bleeding in some women. CORT125134 will not have these effects. The compound is proprietary to Corcept and is protected by composition of matter and method of use patents extending into 2033.