New Androgen Receptor Inhibitor Shows Activity in Metastatic Castration-Resistant Prostate Cancer


Key Points

  • ODM-201 was well tolerated and produced PSA responses at 200 mg, 400 mg, and 1,400 mg daily.
  • PSA response rates were higher among patients who had not received chemotherapy or CYP17 inhibitors.

ODM-201 is a novel androgen receptor inhibitor—structurally distinct from enzalutamide (Xtandi)—that acts via high-affinity binding to the androgen receptor and inhibition of receptor nuclear translocation. In the phase I/II ARADES trial reported in The Lancet Oncology, Fizazi et al identified no maximum tolerated dose and observed prostate-specific antigen (PSA) responses in men with progressive metastatic castration-resistant prostate cancer.

Study Details

In this study, conducted in 23 U.S. and European hospitals, no dose-limiting toxicity or maximum tolerated dose was found at an oral ODM-201 dose range of 200 mg to 1,800 mg daily in the phase I portion.  In the phase II portion, 110 patients were randomly assigned to receive doses of 200 mg (n =38), 400 mg (n = 37), or 1,400 mg (n = 35); four, seven, and three patients treated at these dose levels in the phase I portion were also advanced to phase II evaluation. The primary endpoint was ≥ 50% reduction in serum PSA at week 12.

PSA Response

Among evaluable patients, PSA response at 12 weeks was observed in 29% at 200 mg, 33% at 400 mg, and 33% at 1,400 mg. Response rates were higher among patients who were chemotherapy-naive and had not received CYP17 inhibitor treatment (50%, 69%, and 86%). Follow-up is ongoing.

Adverse Events

No dose-related trends in adverse events were observed. The most common adverse events of any grade in all patients in the phase II study were fatigue/asthenia (34%), back pain (25%), and arthralgia (21%). The most common grade 3 adverse events were fatigue/asthenia, back pain, arthralgia, pain, and anemia, all of which occurred in 2% of patients. Grade 4 adverse events occurred in 2 patients (2%). Treatment was discontinued due to adverse events in 3% of patients, with none of these adverse events being considered related to ODM-201 treatment.

The investigators concluded, “Our results suggest that ODM-201 monotherapy in men with progressive metastatic castration-resistant prostate cancer provides disease suppression and that ODM-201 has a favourable safety profile. These findings support further investigation of clinical responses with ODM-201 in men with castration-resistant prostate cancer.”

Karim Fizazi, MD, of Institut Gustave Roussy, is the corresponding author for The Lancet Oncology article.

The study was funded by Orion Corporation Orion Pharma and Endo Pharmaceuticals Inc. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.