US-based biopharmaceutical firm Arno Therapeutics has enrolled its first patient in a Phase I dose escalation trial evaluating onapristone in post-menopausal women with progesterone receptor (PR) positive tumours, including breast, endometrial and other solid tumours.
The Phase I study will assess onapristone in sustained release and immediate release formulations in about six dose levels (10mg-50mg BID and 100mg QD) in order to identify the recommended Phase II dose as well as determine the overall safety of the drug.
A total of 60 patients are expected to be enrolled in the multi-site trial, which is being conducted in France.
The first patient in the trial has been enrolled by Gustave Roussy Institute of Oncology investigator Andrea Varga.
The company said that onapristone, an oral, anti-progestin hormone blocker, has the potential to be the first approved anti-progestin for oncology indications as well as provide chemotherapy-sparing treatment to cancer patients who express a specific biomarker, as detected by a companion diagnostic under development.
In previous Phase II clinical trials, onapristone has demonstrated anti-tumour activity in patients with breast cancer.
In extensive pre-clinical testing, the drug has also shown the ability to block the activation of the progesterone receptor, which is believed to inhibit the growth of breast, endometrial and other tumours.
The company also said that the activated form of the progesterone receptor (APR) has the potential to function as a biomarker of anti-progestin activity.
For the Phase I trial, the company has engaged Biotrial, a drug evaluation and pharmacology research company that conducted the pharmacokinetic (PK) study, as its contract research organisation.
Arno Therapeutics president and chief executive officer Glenn Mattes said the enrolment of the first patient in the Phase I trial is a milestone for the company.
"We are focused on driving forward the development of onapristone in the most efficient and cost-effective manner and believe it could fill a unique position in the market as there is significant potential for it to be the first approved anti-progestin in oncology," Mattes said.
"We are at the forefront of establishing a genuine appreciation for the role of the progesterone receptor in cancer and the activated form as a biomarker, and we look forward to successfully developing our programme."
Image: Structure of the PGR protein based on PyMOL rendering of PDB 1a28. Photo: courtesy of Emw.