Adjuvant Rezvilutamide Monotherapy for High-Risk Prostate Cancer After Radical Prostatectomy

Rezvilutamide Monotherapy as Adjuvant Treatment for Patients With High Recurrence Risk After Radical Prostatectomy: A Prospective, Multicenter, Single-Arm Study

Prostate cancer patients with high-risk features who undergo radical prostatectomy (RP) are at a significant risk of biochemical recurrence (BCR) and disease progression. While adjuvant androgen deprivation therapy (ADT) with or without radiotherapy is the current standard of care, long-term ADT is associated with substantial adverse effects, including metabolic syndrome, cardiovascular disease, and bone density loss, which negatively impact patients' quality of life. There is an unmet clinical need to optimize adjuvant treatment strategies to improve survival outcomes while minimizing treatment-related toxicity for this high-risk population. Rezvilutamide is a novel, potent, second-generation oral androgen receptor (AR) inhibitor. This prospective, multicenter, single-arm clinical trial aims to evaluate the efficacy and safety of rezvilutamide monotherapy as an adjuvant treatment in patients with localized prostate cancer who have a high risk of recurrence following radical prostatectomy. The study plans to enroll 48 male patients (aged 18-75 years) who have completed radical prostatectomy within 12 weeks, have achieved a postoperative prostate-specific antigen (PSA) level of < 0.1 ng/mL within 8 weeks, and possess a high recurrence risk defined by a CAPRA-S score of ≥ 6. Eligible patients will receive rezvilutamide monotherapy at a dose of 240 mg orally once daily for 12 cycles (28 days per cycle, totaling 48 weeks). The primary endpoint of the study is the 2-year biochemical progression-free survival (bPFS) rate. Secondary endpoints include event-free survival rate, 5-year bPFS, 5-year metastasis-free survival (MFS), testosterone recovery rate and time at 2 years, overall safety, and health-related quality of life assessed by the FACT-P and EPIC-26 questionnaires. By exploring this monotherapy approach, the study hopes to provide a new, effective, and better-tolerated adjuvant treatment option that can improve the prognosis of high-risk patients post-prostatectomy.

Inclusion Criteria:

• Age and Diagnosis: Male patients aged ≥ 18 and ≤ 75 years with histologically or cytologically confirmed prostate adenocarcinoma.

• Disease Stage and Surgery: Localized prostate cancer (assessed by conventional imaging such as CT and bone scan), having undergone radical prostatectomy within 12 weeks prior to enrollment.

• Postoperative PSA: Postoperative prostate-specific antigen (PSA) level < 0.1 ng/mL within 8 weeks after surgery.

• Risk Stratification: Postoperative CAPRA-S score ≥ 6, indicating a high risk of recurrence.

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

• Adequate Organ Function: Must meet the following laboratory criteria:

  1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L (without blood transfusion or G-CSF within 14 days).
  2. Hemoglobin (HGB) ≥ 90 g/L. Platelet count (PLT) ≥ 100 × 10^9/L. (3) Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × upper limit of normal (ULN) (without blood product transfusion within 14 days).

  (4)Creatinine clearance rate ≥ 30 mL/min. (5) Total bilirubin (TBIL) ≤ 1.5 × ULN. (6) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.

• Radiotherapy Intention: Patients who are unfit for or refuse to receive radiotherapy.

• Contraception: Patients of reproductive potential must be willing to use highly effective contraceptive methods during the study and for 12 weeks after the last dose of study drug. I

• informed Consent: Capable of understanding and providing written informed consent (ICF) and willing to comply with study requirements and evaluation schedules.

Exclusion Criteria:

• Histology: Prostate tissue pathology showing neuroendocrine, small cell, or sarcomatoid features.
• Metastasis: Preoperative conventional imaging (e.g., CT or bone scan) indicating pelvic lymph node metastasis (cN1) or distant metastasis (cM1).
• Prior Therapies: Prior androgen deprivation therapy (ADT) (including medical or surgical castration), focal therapy for prostate cancer, or chemotherapy/radiotherapy for prostate cancer.
• Prior Novel Hormonal Agents: Prior treatment with second-generation anti-androgens (e.g., abiraterone, apalutamide, enzalutamide, darolutamide, etc.). ·Recent Surgery: Major surgery requiring general anesthesia (other than radical prostatectomy) within 28 days prior to the first dose of study drug.
• Other Malignancies: History of or concurrent other malignancies within the past 2 years, except for cured non-melanoma skin cancer and superficial bladder tumors (Ta, non-invasive; Tis, carcinoma in situ; and T1).
• Thromboembolic Events: Arterial or venous thromboembolic events (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism) within the past 6 months, or currently receiving therapeutic anticoagulation with warfarin or heparin.
• Cardiovascular Conditions: Heart rate-corrected QT interval (QTc) > 500 ms; severe cardiovascular disease (myocardial ischemia or infarction grade ≥ II, uncontrolled arrhythmias, NYHA class III-IV heart failure, or LVEF < 50% on echocardiogram).
• Allergies: Known allergy to any study drug or its excipients.
• Active Infections/Hepatitis: Active viral hepatitis requiring treatment (HBV DNA ≥ 500 IU/mL for HBV carriers; positive HCV RNA for HCV antibody-positive patients); known human immunodeficiency virus (HIV) infection; or any other active infection.
• Autoimmune Diseases: Active autoimmune disease or history of autoimmune disease requiring systemic treatment, known history of allogeneic organ or hematopoietic stem cell transplant, or long-term high-dose use of corticosteroids or other immunomodulators.
• Systemic Diseases: History of interstitial lung disease or uncontrolled systemic diseases (e.g., diabetes, hypertension, acute lung disease).
• Seizures: History of epilepsy or conditions that may induce seizures.
• Substance Abuse/Compliance: Underlying medical conditions, alcohol/drug abuse, or dependence that would interfere with drug administration, results interpretation, or pose a high risk for complications.
• Sperm Donation/Family Planning: Men engaging in sexual activity with women of childbearing potential unwilling to use a condom with spermicide, unwilling to abstain from sperm donation during the study and for at least 3 months after the last dose, or planning to have children during this period.
• Concurrent Trials: Concurrent participation in another therapeutic clinical study