|Creating the next generation of cancer treatments
October 23, 2014
Arno Therapeutics to Present Encouraging Data from Ongoing Phase I/II Trial Evaluating Onapristone in CRPC at 21st Annual PCF Scientific Retreat
- Favorable safety profile led DRC to open enrollment to all five dose cohorts -
FLEMINGTON, NJ - October 23, 2014 - Arno Therapeutics, Inc. (OTCQB: ARNI), a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, today announced that it will present data from its ongoing Phase I/II clinical trial (NCT02049190) evaluating investigational lead compound onapristone in men with advanced castration-resistant prostate cancer (CRPC) after failure of abiraterone or enzalutamide at the 21st Annual Prostate Cancer Foundation (PCF) Scientific Retreat, being held October 23-25, 2014 at the La Costa Hotel in Carlsbad, California.
The trial is taking place at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust in the UK and is being led by Principal Investigator, Gerhardt Attard, MD, PhD, MRCP, an Academic Medical Oncology Consultant who specializes in the treatment of advanced prostate cancer and in early drug development. Dr. Attard will present the findings, titled, "Phase 1 study of onapristone, a progesterone receptor (PR) antagonist, in castration-resistant prostate cancer (CRPC)" in a poster session on Thursday, October 23 at 8:45-11:00 p.m. PT.
Alex Zukiwski, MD, Chief Executive Officer of Arno Therapeutics, commented, "The findings to date from our ongoing Phase I/II trial of onapristone in metastatic castration-resistant prostate cancer are encouraging as we have observed no dose-limiting toxicities and no significant liver function test abnormalities at the first two dose-levels. This favorable safety profile observed in the first two doses led the independent data review committee to open enrollment to all five dose cohorts, for which we have escalated randomization of patients to the three higher doses. Now that the safety portion of the first stage of the trial is complete, we will continue to evaluate the safety and anti-cancer activity of onapristone across the five dose levels, and look forward to sharing additional findings next year."
The randomized, open-label Phase I/II trial is evaluating onapristone in extended-release tablet formulations in up to five dose levels (10-50 mg BID) in patients with advanced CRPC. The study is being conducted in two stages, with an expansion component; the first stage evaluates dose selection and the second will expand the number of patients at the determined recommended Phase II dose (RP2D) to confirm the safety profile and provide a preliminary assessment of anti-tumor activity.
In stage 1, researchers randomized patients at two dose levels at either 10 or 20 mg onapristone twice a day (BID) with three to six patients per cohort. At baseline, researchers evaluated tumor biopsies of hormone-naïve and castration-resistant study subjects for PR expression, which will support the companion diagnostic being developed to identify patients who are more likely to respond to onapristone. As PR expression in prostate cancer has been reported to increase in CRPC specimens, the transcriptionally activated PR (APR) offers a potential biomarker target in advanced CRPC.
Of the CRPC specimens tested at baseline, 13 of 45 (28.9%) demonstrated PR expression (measured as greater than 1% of cells tested expressing PR) and two of 45 (4.4%) had strong PR expression (measured as greater than 50% of cells tested). To date, 14 patients have been screened, of whom 11 have been enrolled and are being treated. All patients are white males with a median age of 72 years (54–89), an ECOG score of 1, and a baseline prostate-specific antigen (PSA) showing high values (median of 141 ng/dl). No dose-limiting toxicities (DLTs) were identified at the first two dose-levels and no significant liver function test abnormalities were observed. Treatment-emergent adverse events (AEs) of greater than or equal to Grade 2 included fatigue (2 patients), constipation (2 patients), hyponatremia (low sodium level) and aggressive behavior (1 patient), and Grade 4 central retinal artery occlusion, which occurred 14 days after treatment discontinuation (1 patient), but were all considered unrelated to onapristone. Two serious adverse events were reported, but were both also considered unrelated to onapristone. Six of 11 (55%) patients reported drug-related AEs, all Grade 1, with no discontinuations secondary to onapristone-related adverse events. Pharmacokinetics (PK) of the drug also appeared dose proportional.
The DRC has approved the study to proceed to the escalation portion of stage 1 and has opened the next three dosing levels, evaluating onapristone at 30, 40 or 50 mg BID with six randomized patients per cohort. In addition, the APR diagnostic method is being refined and will be used for selective biomarker-driven patient enrichment by way of a design that guarantees greater than 75% of patients at the RP2D are biomarker-positive.
Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials (not sponsored by Arno) to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the PR, which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other, primarily gynecological tumors. APR has the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic currently under development.
About Prostate Cancer
In the United States, prostate cancer is the most frequently diagnosed cancer in men aside from skin cancer. An estimated 233,000 new cases of prostate cancer will be diagnosed during 2014 in the U.S. alone. With an estimated 29,500 deaths expected to occur in 2014, prostate cancer is the second-leading cause of cancer death in men.i
On the global scale, prostate cancer is the fourth most common cancer in both sexes combined and the second most common cancer in men. Worldwide in 2012, an estimated 1.1 million men were diagnosed – accounting for 15 percent of the cancers diagnosed in men – and there were an estimated 307,000 deaths, making prostate cancer the fifth leading cause of death from cancer in men (6.6% of the total men deaths).ii
About Arno Therapeutics
Arno Therapeutics is a clinical stage biopharmaceutical company developing innovative products for the treatment of cancer. Arno has exclusive worldwide rights to develop and market three innovative anti-cancer product candidates. These compounds are in clinical or preclinical development as product candidates to treat hematologic malignancies and solid tumors. For more information about the company, please visit www.arnothera.com.
Forward-Looking Statements: This press release contains forward-looking statements that involve substantial risks and uncertainties. These statements are often, but not always, made through the use of words or phrases such as "anticipates," "expects," "plans," "believes," "intends," and similar words or phrases. These forward-looking statements include, without limitation, statements regarding the timing, progress and anticipated results of the clinical development of onapristone, statements regarding the potential of onapristone as a treatment for prostate and other cancers, statements regarding Arno’s use and development of a diagnostic test to identify patients with APR tumors, as well as Arno's strategy, future operations, outlook, milestones, future financial position, future financial results, plans and objectives. We may not actually achieve these plans, intentions or expectations and Arno cautions investors not to place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. Various important factors could cause actual results or events to differ materially from the forward-looking statements that we make. Such factors include, among others, risks that the results of clinical trials will not support our claims or beliefs concerning the effectiveness of onapristone or any of our other product candidates, our ability to successfully develop a diagnostic to identify APR tumors, our ability to finance the development of our product candidates, regulatory risks, and our reliance on third party researchers and other collaborators. Additional risks are described in the company's Annual Report on Form 10-K for the year ended December 31, 2013. Arno is providing this information as of the date of this press release and does not undertake any obligation to update any forward-looking statements as a result of new information, future events or otherwise.
i International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx
ii International Agency for Research on Cancer. GLOBOCAN 2012: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012. Available at: http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx Last accessed. February 6, 2014.
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