Researchers are looking for a better way to treat men who have high-risk localized prostate cancer, which refers to a type of prostate cancer that is still confined to the prostate gland but has certain characteristics that make it more likely to grow and spread.

The study treatment darolutamide plus androgen deprivation therapy (ADT) is under development as treatment before surgery for men who have high-risk localized prostate cancer. Darolutamide works by blocking the attachment of androgen hormones to androgen receptors in cancer cells, thereby blocking cancer progression and growth. ADT is an established treatment that is used to lower the amount of androgen hormones (e.g., testosterone) in the body.

The main purpose of this study is to learn how the cancer responds to the two different treatment durations (12 weeks or 24 weeks) of darolutamide combined with ADT used before the men undergo surgery to remove the prostate. For this, the researchers will compare the percentage of participants who either achieve complete response to the treatment (where no cancer cells are found) or with condition of minimal residual disease after the treatment (where only a small amount of cancer cells remains).

The study participants will be randomly (by chance) assigned to one of two treatment groups. Depending on the group, they will receive darolutamide tablets by mouth plus ADT administered under the skin for either 12 weeks or 24 weeks. No more than 30 days after the end of the treatments, study participants will be performed with surgery to remove the prostate.

Each participant will be in the study for approximately 29 to 32 months, including a screening phase of up to 28 days, 12 weeks or 24 weeks of treatment depending on the treatment groups, followed by the surgery no more than 30 days after the treatment, and a follow up phase of up to 2 years after the surgery.

2 visits to the study site are planned during the screening phase, followed by 3 to 6 visits (every 28 days) during treatment. The treatment period ends with a visit within 7 days after the last dose of treatment.

During the study, the doctors and their study team will:

• take blood and urine samples
• check the participants' health parameters
• do physical examinations
• check if the participants' cancer has grown and/or spread using CT (computed tomography) or MRI (magnetic resonance imaging) and, if needed, bone scan
• take tumor samples
• ask the participants questions about how they are feeling and what adverse events they are having.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events, irrespective if they think it is related or not to the study treatments.

About 30 days after the last dose of treatment, 5 weeks after the surgery and every 12 weeks thereafter, the study doctors and their team will check the participants' health and any changes in cancer. This follow-up period ends 2 years after the surgery.

Inclusion Criteria:

• Participants must be 18 years or older at the time of signing the informed consent.

• Darolutamide-naïve participants who are with localized prostate adenocarcinoma who plan to receive radical prostatectomy (RP) and defined as high risk with National Comprehensive Cancer Network (NCCN) criteria (version 1.2025).

• No evidence of distant metastasis based on computed tomography (CT), magnetic resonance imaging (MRI), and whole body bone scan (WBBS) within 42 days prior to start of study treatment.

• Candidate for RP with pelvic lymph node dissection (PLND) or extended PLND (ePLND) as per the investigator.

• Participants must have at least one of the following features according to NCCN definition of high-risk:

  • Biopsy Gleason score ≥8, and/or
  • Prostate-specific antigen (PSA) >20 ng/mL measured during Screening and prior to randomization, or
  • Clinical stage ≥ T3a.

• Participants with pelvic lymph node involvement (N1) can be included.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.

Exclusion Criteria:

• Prostate cancer with known neuroendocrine (NE) differentiation or small cell features.

• Evidence of metastatic disease. Minimum imaging requirements to exclude metastatic disease are diagnostic quality imaging of the chest, pelvis, and the abdomen (CT or MRI with intravenous [IV] contrast), and WBBS. Nodal disease below the iliac bifurcation (clinical stage N1) is not an exclusion.

• Intolerant to darolutamide or androgen deprivation therapy (ADT) treatment.

• History of

  • Loss of consciousness or transient ischemic attack or stroke within 6 months prior to randomization, or
  • Significant cardiovascular disease within 6 months prior to randomization.
  • Any contraindications for RP.

• Uncontrolled or treatment-resistant hypertension.

• History of another malignancy within 5 years prior to randomization.

Currently, there is no established plan for the sharing of Individual Patient Data (IPD) from this study. The availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA 'Principles for responsible clinical trial data sharing.' This pertains to the scope, timepoint, and process of data access.

As such, Bayer commits to considering requests from qualified researchers for patient- / study-level clinical trial data, and documents from clinical trials involving medicines and indications approved in the US and EU. However, this commitment does not reflect an active IPD sharing plan. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Researchers can use www.vivli.org to request access to IPD and documents from clinical studies to conduct research. Information on Bayer's criteria for listing studies is provided in the member section of the portal.