ASCO 2017: ARASENS phase 3 trial of ODM-201 in men with metastatic hormone-sensitive prostate cancer

Chicago, IL ( Dr. Matthew Smith and colleagues presented the design for their trial, the ARASENS phase III trial assessing ODM-201 (darolutamide) in men with metastatic hormone-sensitive prostate cancer at the prostate cancer poster session at ASCO 2017. Even with first line therapy (ADT +/- docetaxel or abiraterone, based on the LATITUDE and STAMPEDE studies presented this week), most patients with metastatic hormone-sensitive prostate cancer (mHSPC) progress to castration-resistant prostate cancer (CRPC).

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 the phase 1 ARAFOR1 and phase 1/2 ARADES2 trials, ODM-201 had antitumor activity and was well tolerated in men with mCRPC. The objective of this trial is to evaluate ODM-201 plus standard ADT + docetaxel in men with metastatic disease.

This international, randomized, double-blind, placebo-controlled, phase III trial is being conducted in 23 countries. Approximately 1,300 men with newly diagnosed metastatic hormone sensitive prostate cancer will be randomized 1:1 to either ODM-201 600 mg twice daily (2×300 mg tablets) orally or placebo, both with ADT + docetaxel (6 cycles after randomization). Patients will be stratified by extent of disease and alkaline phosphatase levels. Inclusion criteria include: (i) histologically confirmed prostate cancer with documented metastases, started ADT ± first-generation anti-androgen therapy ≤12 weeks before randomization, and ECOG performance status 0 or 1. The primary objective is to show superior overall survival (OS) with ODM-201 versus placebo, both with ADT + docetaxel. Secondary end points include (i) time to CRPC, (ii) initiation of subsequent anticancer therapy, (iii) symptomatic skeletal event-free survival (SSE-FS), (iv) time to first SSE, (v) initiation of opioid use, (vi) pain progression, and (vii) worsening of physical symptoms, all measured at 12-week intervals.

This trial is currently open for enrollment in 23 countries worldwide, with the first patient visit occurring in November 2016.
Clinical trial: NCT02799602

Presented By: Matthew R. Smith, MD, PhD, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA

Co-Authors: Fred Saad, Maha Hussain, Cora N. Sternberg, Karim Fizazi, E. David Crawford, Karin Sayuri Yamada, Christian Kappeler, Iris Kuss, Bertrand F. Tombal

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
Twitter: @zklaassen_md

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

1. Massard C, Penttinen HM, Vjaters E, et al. Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naïve Metastatic Castration-resistant prostate cancer: An Open-Label Phase 1 study. Eur Urol 2016 May;69(5):834-840. 

2. Fizazi K, Massard C, Bono P, et al. Activity and safetly of ODM-201 in patients with progressive metastatic castration-resistant prostate cancer (ARADES): an open-label phase 1 dose-escalation and randomized phase 2 dose expansion trial. Lancet Oncol 2014 Aug;15(9):975-985.
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