ARADES: A first-in-man study of ODM-201

A proof-of-concept study of ODM-201 in patients with progressive castration-resistant prostate cancer

PSA change from baseline to 12 weeks observed in the ARADES study

PSA change from baseline to 12 weeks observed in the ARADES study
Credit: Dr Christophe Massard
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The hallmark of castration-resistant prostate cancer (CRPC) is persistent, high level androgen receptor expression and resistance to conventional anti-androgens. ODM-201 is a new generation, androgen receptor antagonist that does not enter the brain in non-clinical models, unlike other anti-androgens. It inhibits androgen receptor function by blocking nuclear translocation. ODM-201 has no agonist activity when the androgen receptor is over-expressed.

ARADES is a first-in-man, multi-centre phase I/II dose-escalation trial in patients with progressive metastatic CRPC who were either treatment naive or had received prior chemotherapy. The study was started in March 2011 to assess safety, pharmacokinetics, and anti-tumour effects of ODM-201.
The study planned to enrol three to six patients per dose-escalation cohort on the preplanned doses of 100, 200, 300, 500, 700 and 900 mg twice daily. Once the safety of an administered dose was established, next dose level was administered, and patients at the previous dose level were allowed to continue treatment until progression or an intolerable adverse event occurred. The dose-escalation part of the study is ongoing at 700 mg dose level twice daily.

The researchers led by Dr Christophe Massard from Institute Gustave Roussy, villjuif, France reported at the ESMO 2012 Congress of the European Society for Medical Oncology in Vienna that to date, 21 patients have tolerated ODM-201 with no significant treatment emergent adverse events. The most common adverse events were asthenia, nausea and diarrhoea.

A prostate specific antigen (PSA) response, defined as a decrease of 50% or more of PSA levels, was achieved by 13 (87%) of 15 patients evaluable at 12 weeks, including all six patients who had previously received docetaxel. All evaluable patients to date achieved a partial response or remained stable according to RECIST criteria at 12-weeks. The pharmacokinetics is linear in dose range 100 - 300 mg x 2 and the steady state is reached at day 8.

According to the study authors, these early results are very promising, and such are rarely seen in early trials. ODM-201 might be a new hormonal treatment option, and its efficacy-safety profile seems to be very promising in prostate cancer patients.

Unlike other anti-androgens, ODM-201 has minimal or no brain entrance, and thus no testosterone increase in animal models. Therefore ODM-201 could be a promising new drug option for patients with metastatic or non-metastatic prostate cancer, but the results should be confirmed in bigger patient population first.