LBA25_PR - ARADES trial: A first-in-man, open-label, phase I/II safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients (pts) with progressi...

Date 30 September 2012
Event ESMO Congress 2012
Session Genitourinary tumors, prostate
Presenter Christophe Massard
Authors C. Massard1, N. James2, S. Culine3, R. Jones4, A. Vuorela5, M. Mustonen5
  • 1Sitep, Institute Gustave Roussy, 94800 - Villejuif/FR
  • 2Oncology - University Hospitals, Queen Elizabeth Hospital, B15 2TH - Birmingham/UK
  • 3Oncology, Hospital Saint Louis, 75475 - PARIS CEDEX10/FR
  • 4Cardiff University, Velindre Cancer Centre, CF10 3AX - Cardiff/UK
  • 5Research And Development, Orion Corporation Orion Pharma, 02101 - Espoo/FI



Background: CRPC is characterized by persistent, high level androgen receptor (AR) expression and resistance to conventional antiandrogens such as bicalutamide. ODM-201 is a novel, new generation, AR antagonist that does not, unlike other antiandrogens, enter brain in nonclinical models, and that lacks the partial agonist activity seen with bicalutamide in the setting of AR overexpression. Unlike bicalutamide, ODM-201 inhibits AR function by blocking nuclear translocation, and has no agonist activity when AR is overexpressed.

Methods: A first-in-man, multi-center Phase I/II dose-escalation trial in progressive mCRPC pts with and without prior chemotherapy was started in March 2011 to assess safety, pharmacokinetics, and anti-tumor effects. ODM-201 was administered orally, twice daily with food. In the study, three to six pts were to be enrolled 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 pts with previous dose level were allowed to continue treatment until progression or intolerable adverse event (AE).

Results: The dose-escalation part of the study is still ongoing at 700 mg x 2 dose level. In 21 treated pts, ODM-201 has been well-tolerated to date, with no significant treatment emerged AEs. The most common AEs were asthenia, nausea and diarrhea. A PSA response (defined as = 50% PSA decrease) was obtained in 13 (87%) of 15 patients currently evaluable at 12-weeks. All 6 docetaxel-pretreated pts had a PSA decrease at 12-weeks. All evaluable pts so far 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.

Conclusions: ODM-201, a uniquely designed AR antagonist, showed good tolerability and high anti-cancer activity in pts with mCRPC, including docetaxel-pretreated pts, in this Phase I/II trial. Expansion of Phase II trial has started in June 2012. ARADES trial is sponsored by Orion Corporation Orion Pharma and Endo Pharmaceuticals. NCT01317641.