770TiP - EMBARK: A phase 3, randomized, efficacy and safety study of enzalutamide plus leuprolide, enzalutamide monotherapy and placebo plus leuprolide in m...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Prostate Cancer
Presenter Kurt Miller
Citation Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372
Authors K. Miller1, P. Mulders2, S.J. Freedland3, H. Scher4, N. Shore5, E. Park6, A. Krivoshik7, D. Phung8, K. Modelska9, P. Scardino10
  • 1Department Of Urology, Charité – Universitätsmedizin Berlin, 10117 - Berlin/DE
  • 2Department Of Urology, Radboud University Medical Centre Nijmegen, Nijmegen/NL
  • 3Surgery, Cedars-Sinai Medical Center, Los Angeles/US
  • 4Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York, NY/US
  • 5Urology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 6Clinical Development, Medivation, Inc., San Francisco/US
  • 7Medical Oncology, Astellas Pharma Global Development, Inc., 60062 - Northbrook/US
  • 8Biostatistics, Astellas Pharma, Leiden/NL
  • 9Clinical Development, Medivation Inc,, San Francisco/US
  • 10Urology, Memorial Sloan-Kettering Cancer Center, New York/US

Abstract

Background

After radical prostatectomy or radiotherapy, about 1 of 4 men with adenocarcinoma of the prostate will develop a biochemical recurrence manifested by increasing levels of prostate-specific antigen (PSA). Of these, approximately 1 of 3 will eventually develop clinically detectable metastatic disease. To date, there is no approved therapy for patients who have PSA relapse after surgery and/or radiotherapy and are at high risk for metastatic disease. Androgen deprivation is the de facto standard and most commonly prescribed treatment in this setting. The EMBARK trial is designed to address this unmet need in high-risk, nonmetastatic, hormone-sensitive prostate cancer patients who recur after primary therapy.

Trial design

The EMBARK trial will randomize approximately 1860 subjects globally, across 200 international sites, into 3 treatment arms: leuprolide + enzalutamide, leuprolide + placebo and enzalutamide monotherapy. Enrolment is ongoing since Jan 2015. Subjects must fulfil the following entry criteria indicative of having biochemical relapse and high-risk disease: PSA doubling time ≤ 9 months; screening PSA threshold of ≥ 2.0 ng/mL for subjects who had prior radical prostatectomy or ≥ 5.0 ng/mL and ≥ nadir + 2 ng/mL for subjects who had radiotherapy as the primary therapy; androgen deprivation therapy ≤ 36 months in duration and ≥ 9 months before randomization and administered only in the neoadjuvant/adjuvant setting; no evidence of soft-tissue or bone metastases at the time of enrollment; and testosterone level > 150 ng/dL. In each arm, subjects will be evaluated every 12 wks through the treatment course. Imaging studies with computed tomography/magnetic resonance imaging and bone scans will be performed every 25 wks until the primary efficacy endpoint of metastasis-free survival is met. Subjects are allowed 1 treatment suspension (of the study drugs) at wk 37 if the PSA levels are 

Clinical trial identification

NCT02319837

Legal entity responsible for the study

Medivation, Inc. and Astellas Pharma, Inc.

Funding

Medivation, Inc. and Astellas Pharma, Inc.

Disclosure

K. Miller: reports consulting fees: Medivation, Astellas; outside submitted work consulting fees: Astellas, Amgen, Janssen-Cilag, Medivation, Novartis, Roche, and speaker bureau fees: Novartis, Janssen-Cilag, Pierre-Fabre.

P. Mulders: receives consulting fees and participates in review activities from Janssen J&J; outside submitted work consultancy and lectures/speaker bureaus: AstraZeneca, Astellas, GlaxoSmithKline; grants to institution: Bayer.

S.J. Freedland: is a consultant to Medivation and Astellas.

H. Scher: reports grants: Medivation, personal fees: Endo/Orion, Ferring, Chugai, non-financial support from Exelisis, Janssen, Novartis, BMS, Celgene, Takeda Millennium, outside submitted work: Astellas, Novartis, AZ, Genentech, Endocyte, Pfizer, Sanofi-Aventis.

N. Shore: reports personal fees from Astellas, personal fees from Medivation, during the conduct of the study.

E. Park: employee at Medivation Inc.

A. Krivoshik: an employee of Astellas and hold stock in Abbott and Abbvie.

K. Modelska: reports personal fees and other from Medivation, during the conduct of the study

All other authors have declared no conflicts of interest.