Phase I/II data on ODM-201 in mCRPC; and a Phase III trial in nmCRPC

ODM-201 is a new androgen receptor  inhibitor, initially developed by a Finnish company called Orion and now being developed by Orion in partnership with the German pharmaceutical company, Bayer.

This week’s issue of the The Lancet Oncology includes an article by Fizazi et al. on the results of a Phase I/II trial of ODM-201 in the treatment of metastatic, castration-resistant prostate cancer (mCRPC) — the so-called ARADES study.

In this study, ODM-201 was tested in two phases and at six different dose levels (200, 400, 600, 1000, 1,400, and 1,800 mg, each given once daily). However, we shall focus on the Phase II component of the trial, in which patients were randomized to receive one of the three doses of ODM-201 that seems to be both active and safe based on the Phase I data. These were doses of 200, 400, and 1,400 mg, again given once daily.

In the Phase II component of the trial, the primary study endpoint was the proportion of patients who received one or more dose of ODM-201 in this phase of the trial and who had a decrease in their PSA level of ≥ 50 percent from their baseline level at week 12 of the study.

The study enrolled patients at 23 institutions in Europe and the USA. All eligible patients had to have progressive mCRPC, castrate levels of testosterone (i.e., a serum T level of < 50 ng/dl).

The Phase II component of the trial included a total of 110 men who were randomized to treatment with ODM-201 at 200, 400, or 1,400 mg once daily, as well as another 14 patients who had been treated with ODM-201 at these dose levels in Phase I of the trial, i.e., 124 patients in total.

Here are the core findings from the Phase II portion of the trial:

  • The most common treatment-emergent adverse events were
    • Fatigue or asthenia in 15/124 patients (12 percent)
    • Hot flashes in 6/124 patients (5 percent)
    • Decreased appetite in 5/124 patients (4 percent).
  • One patient (< 1 percent) had a grade 3 treatment-emergent adverse event (fatigue).
  • No patients had a treatment-emergent grade 4 adverse event.
  • 110/124 patients enrolled were eligible for assessment at 12 weeks of follow-up
    • 38 patients who received ODM-201 at 200 mg once daily
    • 39 patients who received ODM-201 at 400 mg once daily
    • 33 patients who received ODM-201 at 1,400 mg once daily
  • The numbers of patients who demonstrated a reduction in their PSA level of 50 percent or greater at 12 weeks were
    • 11/38 (29 percent) in the 200 mg group
    • 13/39 (33 percent) in the 400 mg group
    • 11/33 (33 percent) in the 1,400 mg group

The authors conclude that ODM-201 does have the potential to suppress progression of prostate cancer in men with mCRPC; that ODM-201 has a “favorable” safety profile; and that further studies should be carried out in men with advanced disease. What this study has not given us any information about as yet is the potential impact of treatment with ODM-201 on long-term survival.

Information about a follow-up Phase III clinical trial of ODM-201 is already available on the web site, and this trial was scheduled to start enrolling a total of 1,500 patients this month (July 2014). The Phase III trial will randomize patients with high-risk, non-metastatic, castration-resistant prostate cancer (nmCRPC) to either ODM-201 (two 300 mg tablets twice daily, i.e., 1,200 mg/day) or to equivalent doses of a placebo, and it is expected to demonstrate results by some time in 2020 (or perhaps earlier). The primary endpoint of this trial will be metastasis-free survival; overall survival will be one of several secondary endpoints. Contact information for patients interested in considering enrollment in this trial is available on the web page referred to immediately above.

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