Phase 1/2 Trial Update of ODM-201 for Metastatic Castration-Resistant Prostate Cancer

(ChemotherapyAdvisor) – The investigational androgen receptor (AR) agonist ODM-201 is well tolerated and exhibits antitumor activity among patients with metastatic castration-resistant prostate cancer (mCRPC), according to data from a Phase 1/2 proof-of-concept study presented at the European Society for Medical Oncology (ESMO) annual meeting in Vienna, Austria.

“ODM-201 might be a new hormonal treatment option, and its efficacy-safety profile seems to be very promising in prostate cancer patients," reported senior author Christophe Massard, MD, at the Department of Medical Oncology, Institut Gustave Roussy, in Villejuif, France.

The ODM-201 dose-escalation trial found that 13 of 15 (87%) study participants demonstrated PSA declines ≥50% at 12 weeks, without significant treatment-related adverse events, Dr. Massard reported. Another 6 patients who were pretreated with docetaxel also all experienced PSA declines ≥50% at 12 weeks.

Oral ODM-201 was administered twice daily with food. Cohorts of 3–6 patients received preplanned doses of 100, 200, 300, 500, 700 and 900mg twice daily, with escalation to the subsequent dose following confirmation of safety of each previously-administered dose. 

“The dose-escalation part of the study is still ongoing at 700mg x 2 dose level,” the coauthors reported. “The pharmacokinetics is linear in dose range 100–300mg x 2 and the steady state is reached at Day 8.”

Unlike other antiandrogens, preclinical data indicates ODM-201 has very little if any penetration of the blood/brain barrier.

“Unlike bicalutamide, ODM-201 inhibits AR function by blocking nuclear translocation, and has no agonist activity when AR is overexpressed,” reported Dr. Massard.

The most common treatment-related adverse events were asthenia, nausea, and diarrhea.

“The results need to be confirmed in bigger patient population, of course,” Dr. Massard added.

ARADES trial is a first-in-man, open-label, safety, pharmacokinetic, and proof-of-concept study of ODM-201 in patients diagnosed with progressive mCRPC. Based on results from the Phase 1 trial, expansion of the Phase 2 trial was initiated in June 2012. ARADES trial is sponsored by Orion Corporation Orion Pharma and Endo Pharmaceuticals.

ESMO Abstract (#LBA25_PR)