A Phase 3 Study of Deutenzalutamide in Patients With High-Risk BCR Prostate Cancer

Prior treatment

• Prior or present evidence of distant metastatic disease as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) for soft tissue disease and whole-body radionuclide bone scan for bone disease. Patients with soft tissue pelvic disease may be eligible if the short axis of the largest lymph node is \<20 mm for lymph nodes below aortic bifurcation. If the screening bone scan shows a lesion suggestive of metastatic disease, the patient will be eligible only if a second imaging modality (CT, or MRI) does not show bone metastasis. If the imaging results are equivocal or consistent with metastasis by central radiology review, the patient is not eligible for enrollment.
• Prior hormonal therapy. Neoadjuvant/adjuvant therapy to treat prostate cancer ≤36 months in duration before randomization, or a single dose or a short course (≤6 months) of hormonal therapy given for rising PSA is allowed.
• Prior treatment with second-generation androgen receptor inhibitors (enzalutamide, darolutamide, apalutamide, rezvilutamide, deutenzalutamide, etc.), CYP17 inhibitors (abiraterone or ketoconazole, etc.), chemotherapy (docetaxel, etc.), immunotherapy (PD-1/PD-L1 inhibitors, etc.), or targeted therapy (PARP inhibitors, AKT inhibitors, etc.).
• Prior or planned bilateral orchiectomy.
• Major surgery within 4 weeks before randomization date.
• Treatment with 5-α reductase inhibitors (finasteride, dutasteride) within 4 weeks before randomization date.
• For patients who had a prior radical prostatectomy, a suitable candidate for salvage radiotherapy as determined by the investigator in consideration of appropriate guidelines.
• Participation in a clinical study of an investigational agent that inhibits the androgen receptor or androgen synthesis (TAK-700, apalutamide, darolutamide, etc.); however, patients who received placebo are allowed.
• Use of any other investigational agent within 4 weeks before randomization date.
• History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke or significant brain trauma). History of loss of consciousness (unless of cardiac origin) or transient ischemic attack within 12 months before randomization.
• Contraindication to the use of androgen deprivation therapy (ADT).
• Ongoing drug or alcohol abuse as per investigator judgment.
• Any concurrent disease, infection, or comorbid condition that interferes with the ability of the patient to participate in the study, which places the patient at undue risk, or complicates the interpretation of data, in the opinion of the investigator or medical monitor.

Other illness

• 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. The medical monitor and investigator must agree that the possibility of recurrence is remote.
• Gastrointestinal disorder affecting drug absorption or swallowing.
• History of allogeneic bone marrow transplantation or organ transplantation requiring continued medical treatment.
• Known congenital or acquired immunodeficiency, active hepatitis, active tuberculosis, and other active infections.
• Known hypersensitivity reaction to deutenzalutamide or any of capsule components (polyethylene glycol hydroxystearate, butylated hydroxyanisole, and butylated hydroxytoluene).

Lab values

• Clinically significant cardiovascular disease including the following:
  • Myocardial infarction within 6 months before screening;
  • Unstable angina within 3 months before screening;
  • New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure unless a screening echocardiogram or multigated acquisition scan performed within 3 months before the randomization date demonstrates a left ventricular ejection fraction ≥45%;
  • History of clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
  • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place;
  • Screening electrocardiogram (ECG): heart rate ≤50 beats per minute (bradycardia); QTc interval \>500 ms;
  • Hypotension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \<90 mmHg at screening;
  • Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg at screening.

Other

• In the investigator's opinion, the participant is unsuitable for participation in this study (eg, not consistent with the most beneficial treatment for the participant, participant compliance).

• Age 18 years or older men, be willing and able to provide informed consent.
• 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. Prostate cryoablation is not considered definitive therapy for this study, but its prior use is not exclusionary.
• BCR prostate cancer, PSA doubling time (PSADT)≤9 months as calculated by the sponsor.
• Screening PSA by the local laboratory as described in the protocol for patients who had radical prostatectomy (with or without radiotherapy) as primary treatment for prostate cancer and for patients who had radiotherapy only as primary treatment for prostate cancer .
• Serum testosterone by the local laboratory ≥150 ng/dL (5.2 nmol/L) at screening.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at screening.
• Estimated life expectancy of ≥12 months.
• Able to swallow the study drug and comply with study requirements.
• Has adequate organ function.
• Must be willing to use reliable contraceptive measures (eg, condom) and refrain from sperm donation throughout the study and through 3 months after the last dose of study drug.