Arno Therapeutics, Inc., a clinical stage biopharmaceutical company focused on the development of oncology therapeutics, has announced that it has enrolled the first patient in a Phase I/II trial (NCT02049190) evaluating its lead compound onapristone in men with advanced castration-resistant prostate cancer (CRPC) after failure of abiraterone or enzalutamide. Patient enrollment of this study follows approval of an Investigational Medicinal Product Dossier from the United Kingdom (UK) Health Authority, Medicines and Healthcare products Regulatory Agency, ethics committee authorization and subsequent site authorization.

Glenn Mattes, President and Chief Executive Officer of Arno Therapeutics, remarked, "Globally, prostate cancer is the second most common cancer in men, and the fifth leading cause of death from cancer in men, with an estimated 1.1 million new cases diagnosed and 307,000 deaths during 2012 alone, according to the International Agency for Research on Cancer. These numbers are staggering, and our ultimate goal is to evaluate onapristone in the subset of advanced CRPC patients who are more likely to respond to this personalized treatment, for which there is an immense unmet medical need. The trial marks Arno's second Phase I study actively enrolling this year and we are excited by the momentum generated thus far."

Onapristone is an oral, anti-progestin hormone blocker that has been shown in previous Phase II clinical trials to exhibit anti-tumor activity in patients with breast cancer. In pre-clinical testing, onapristone has been shown to block the activation of the progesterone receptor (PR), which is believed to be a mechanism that inhibits the growth of APR-driven breast, endometrial and other tumors. Tests for the activated form of the progesterone receptor (APR) have the potential to function as a biomarker of anti-progestin activity, as detected by a companion diagnostic under development.

The randomized, open-label trial is currently enrolling patients and is designed to evaluate the safety and anti-cancer activity of onapristone in the select patient population. This single-site trial is taking place at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust in the UK and additional UK sites are planned. The study is expected to enroll a total of 60 patients. Arno has engaged Biotrial, a drug evaluation and pharmacology research company, as its contract research organization for this trial.

Professor Johann de Bono, MD, PhD, MSc, FRCP, Professor of Experimental Cancer Medicine at The Institute of Cancer Research (ICR) and Honorary Consultant in Medical Oncology at The Royal Marsden, and an investigator for the trial, said, "Advanced prostate cancer remains a difficult disease to treat due to the development of various resistance mechanisms. We are very interested in developing new personalized therapies to improve treatment outcomes for these patients. Through Arno Therapeutics' early trial in advanced castration-resistant prostate cancer, we hope to gain a deeper understanding of the safety profile and potential anti-cancer activity of onapristone with the goal of accelerating the development of the APR biomarker and this targeted anti-progestin."

Onapristone is also being developed for other indications including breast and endometrial cancers. The potential treatment is concurrently being evaluated in a Phase I clinical trial in France in women who have progesterone receptor expressing tumors. This targeted therapy has the potential to be the first approved anti-progestin for oncology indications and provide chemotherapy-sparing treatment to cancer patients who express a specific biomarker.

The Phase I/II study will evaluate onapristone in extended-release tablet formulations in up to five dose levels (10-50 mg BID) in patients with advanced CRPC in which PR may be contributing to tumor progression. Study subjects will be evaluated for whether their tumors express APR, which may help identify patients who are more likely to respond to onapristone. A second cohort of patients will be included at the recommended Phase II dose to gain additional understanding of the onapristone safety profile and potential anti-cancer activity.

Alex Zukiwski, MD, Chief Medical Officer of Arno Therapeutics, commented, "Tolerance to chemotherapy and various targeted therapies is known to be different in males undergoing androgen deprivation treatment. While the percentage of castration-resistant prostate cancer that is APR positive remains to be determined, the initial series of preclinical tumor specimens we examined has demonstrated evidence of APR, and we are looking forward to evaluating the safety and anti-cancer activity of onapristone in this patient population."