Alicia Morgans, MD, highlights the phase 3 ARASTEP trial

The phase 3 ARASTEP trial (NCT05794906) is ongoing to assess the combination of darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) vs ADT alone in the treatment of patients with high-risk biochemical recurrence (BCR) of prostate cancer.¹

In a recent interview with Urology Times®, Alicia K. Morgans, MD, MPH, walked through the design of the study, which was shared during the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

“We're trying to understand the way that use of a sustained and intensive hormonal therapy combination can contribute to hopefully prolonging the time until patients have relapse or progression of their disease vs ADT alone,” Morgans noted.

Morgans is a genitourinary medical oncologist and associate professor of medicine at Harvard Medical School as well as the director of the survivorship program at Dana-Farber Cancer Institute in Boston, Massachusetts.

The randomized study plans to enroll a total of 750 patients across 23 countries.² BCR is determined by a rising prostate-specific antigen (PSA) level as well as at least 1 positive lesion on PSMA-PET.

According to Morgans, “This is critically important because it sets it apart from other studies that are just looking at PSA relapse in this setting. All patients have to have PSMA-PET positive disease.”

Patients must also have had prior treatment with either radiotherapy or radical prostatectomy with or without radiotherapy, a serum testosterone level of 150 ng/dL or less, and an ECOG performance status of 0 or 1.

Those included in the study will be randomly assigned 1:1 to receive the combination of 600 mg darolutamide plus ADT or ADT alone for 24 months until disease progression, unacceptable toxicity, or study withdrawal. The primary end point is radiographic progression-free survival. Secondary end points include metastasis-free survival, time to castration-resistant prostate cancer, overall survival, and safety.

Primary completion of the study is expected in July 2027.

REFERENCES

1. A study to compare darolutamide given with androgen deprivation therapy (ADT) with ADT in men with hormone sensitive prostate cancer and raise of prostate specific antigen (PSA) levels after local therapies (ARASTEP). ClinicalTrials.gov. Last updated June 6, 2025. Accessed June 27, 2025. https://clinicaltrials.gov/study/NCT05794906

2. Morgans A, Niazi T, Shore N, et al. Darolutamide plus androgen deprivation therapy (ADT) in patients with high-risk biochemical recurrence (BCR) of prostate cancer: A phase 3, randomized, double-blind, placebo-controlled study (ARASTEP). J Clin Oncol. 2025;43(5). doi:10.1200/JCO.2025.43.5_suppl.TPS43