ARASENS phase 3 trial of ODM-201 in men with metastatic hormone-sensitive prostate cancer (mHSPC)

TPS5092 Background: Androgen deprivation therapy (ADT) ± docetaxel is recommended first-line therapy for mHSPC, but most patients progress to castration-resistant PC (CRPC). BAY-1841788 (ODM-201) is an investigational oral androgen receptor (AR) antagonist that has a unique chemical structure designed to block the growth of cancer cells through binding to the AR with high affinity and inhibiting the receptor function. In preclinical studies, ODM-201 and its main circulating metabolite are active also in known AR mutants (eg, W742L, F877L), and have been found to have negligible blood-brain barrier penetration. In the phase 1 ARAFOR and phase 1/2 ARADES trials, ODM-201 had antitumor activity and was well tolerated in men with mCRPC (Massard et al. Eur Urol. 2016;69:834‒840; Fizazi et al. Lancet Oncol. 2014;15:975‒985). Given this promising activity in mCRPC, the ARASENS trial is evaluating ODM-201 plus standard ADT + docetaxel in men with metastatic disease (mHSPC). Methods: This international, randomized, double-blind, placebo-controlled, phase 3 trial (NCT02799602) is being conducted in 23 countries. ~1300 men with newly diagnosed mHSPC will be randomized 1:1 to either ODM-201 600 mg twice daily (2×300 mg tablets) orally with food or placebo, both with ADT + docetaxel (6 cycles after randomization), and stratified by extent of disease and alkaline phosphatase levels. Key inclusion criteria are histologically or cytologically confirmed PC with documented metastases, started ADT ± first-generation anti-androgen therapy ≤12 weeks before randomization, and Eastern Cooperative Oncology Group performance status 0 or 1. The primary objective is to show superior overall survival with ODM-201 vs placebo, both with ADT + docetaxel. Secondary end points include time to CRPC, initiation of subsequent anticancer therapy, symptomatic skeletal event-free survival (SSE-FS), time to first SSE, initiation of opioid use, pain progression, and worsening of physical symptoms, all measured at 12-week intervals. Safety will be assessed by adverse events. The trial is open for enrollment; first patient first visit was in November 2016 and > 10 sites are open for recruitment and enrolling patients. Clinical trial information: NCT02799602.