Safety and Efficacy Study of Enzalutamide Plus Leuprolide in Patients With Nonmetastatic Prostate Cancer (EMBARK)

The purpose of this study is to assess enzalutamide plus leuprolide in patients with high-risk nonmetastatic prostate cancer progressing after radical prostatectomy or radiotherapy or both. The randomized / blinded portion of the study is now completed following primary endpoint analyses. The study remains ongoing in open label format.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features;
* Prostate cancer initially treated by radical prostatectomy or radiotherapy (including brachytherapy) or both, with curative intent;
* PSA doubling time ≤ 9 months;
* Screening PSA by the central laboratory ≥ 1 ng/mL for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and at least 2 ng/mL above the nadir for patients who had radiotherapy only as primary treatment for prostate cancer;
* Serum testosterone ≥ 150 ng/dL (5.2 nmol/L).

Exclusion Criteria:

* Prior or present evidence of distant metastatic disease as assessed by radiographic imaging;
* Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤ 36 months in duration and ≥ 9 months before randomization, or a single dose or a short course (≤ 6 months) of hormonal therapy given for rising PSA ≥ 9 months before randomization is allowed.;
* Prior cytotoxic chemotherapy, aminoglutethimide, ketoconazole, abiraterone acetate, or enzalutamide for prostate cancer;
* Prior systemic biologic therapy, including immunotherapy, for prostate cancer;
* Major surgery within 4 weeks before randomization;
* Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks of randomization;
* Known or suspected brain metastasis or active leptomeningeal disease;
* History of another invasive cancer within 3 years before screening, with the exception of fully treated cancers with a remote probability of recurrence

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• DERIVEDShore ND, De Giorgi U, Tutrone RF, Bailen JL, Roos EPM, Kliment J, Marx G, Karsh LI, Ramirez-Backhaus M, Uchio EM, Supiot S, Tang Y, Rosbrook B, Haas GP, Rosales M, Zohren F, Tarazi J, Freedland SJ. Enzalutamide Monotherapy for the Treatment of Prostate Cancer With High-Risk Biochemical Recurrence: EMBARK Secondary End Points. J Urol. 2026 Apr;215(4):396-407. doi: 10.1097/JU.0000000000004879. Epub 2025 Dec 5. PMID 41349040
• DERIVEDShore ND, Luz MA, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Kalac M, Sridharan S, Rosales M, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Wang F, Freedland SJ. Improved Survival with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2026 Feb 5;394(6):563-575. doi: 10.1056/NEJMoa2510310. Epub 2025 Oct 19. PMID 41124201
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