Study of Relugolix in Men With Metastatic Castration-Sensitive Prostate Cancer or Non-Metastatic or Metastatic Castration-Resistant Prostate Cancer

Prior treatment

• Received combination treatment with a GnRH analog or GnRH receptor antagonist with either abiraterone acetate plus a corticosteroid (Part 1) or apalutamide (Part 2) in patients with mCSPC (Part 1 and Part 2) or nmCRPC (Part 2) for a total duration \> 24 months or in patients with mCRPC (Part 1) for a total duration \> 6 months;
• Is scheduled or anticipates being scheduled for major surgery during the study treatment period;
• A medical history within 6 months prior to the screening visit or a current diagnosis of any of the following:
  • Myocardial infarction;
  • Unstable angina;
  • Unstable symptomatic ischemic heart disease;
  • Congestive heart failure classified as NYHA class III or IV heart failure;
  • Thromboembolic event(s) (eg, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular event\[s\]);
  • Any other significant cardiac condition (eg, pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease);
• Received an investigational drug within 28 days or 5 half-lives, whichever is longer, prior to the baseline (Day 1) visit;
• Prior use of any prohibited medication(s) and restrictive medication(s) without the appropriate washout period or use of a prohibited medication during the study treatment period is planned;

Other illness

• A medical history of brain or hepatic metastases based on radiologic evidence or a medical history of surgical castration;
• Known hepatic disease, including alcoholic liver disease or viral hepatitis such as hepatitis A (hepatitis A virus IgM positive), chronic hepatitis B (HbsAg positive), or chronic hepatitis C (HCV antibody positive, confirmed by HCV RNA) or clinical signs of hepatic disease such as jaundice;
• Uncontrolled hypertension;
• Positive HIV;
• Medical history of a bleeding disorder or current clinical evidence of gastrointestinal bleeding or active bleeding from another anatomical location;
• A medical history within 1 year of the screening visit of drug or alcohol abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders V;
• A contraindication or known history of hypersensitivity to any of the study treatments or components thereof, or has a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates study participation;
• Any other medical or psychiatric condition that, in the opinion of the investigator, would interfere with accomplishing the study objectives or the patient completing the study;

Lab values

• Abnormal clinical laboratory test value(s) at the screening visit or prior to the baseline (Day 1) visit including:
  • Serum creatinine \> 2.0 mg/dL;
  • Platelets \< 100 × 103/μL;
  • Hemoglobin \< 10.0 g/dL;
  • Leukocytes (WBC) \< 3 × 103/μL;
  • Absolute neutrophil count \< 1.5 × 103/μL;
  • Hemoglobin A1c (HbA1c) \> 8%; Note (Part 3 only): Transfusions and/or administration of growth factors are permitted as indicated for the clinical management of docetaxel-related hematologic effects and in accordance with the investigator's judgement.

Age

• A current diagnosis of a malignancy other than prostate cancer, with the exception of any of the following:
  • Adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of any type;
  • Adequately treated Stage I cancer that is currently in remission and has been in remission for ≥ 2 years;
  • Any other cancer from which the patient has been disease-free for ≥ 3 years;

Other

• A patient will not be eligible for inclusion in the study if any of the following criteria apply:
• An abnormal ECG;
• Hypotension;
• Bradycardia;
• Is a study site employee or is a primary family member (spouse, parent, child, or sibling) of a site employee involved in the conduct of the study.

• A previous diagnosis of adenocarcinoma of the prostate confirmed by histologic or cytologic evidence and with a documented medical history of either:
  • mCSPC (Parts 1, 2, and 3) defined as having at least two of three risk factors at the baseline (Day 1) visit:
  • Total Gleason score of ≥ 6; and
  • Presence of ≥ 2 metastatic lesions on bone scan; OR
  • Radiologic evidence of measurable visceral metastases with exception of hepatic metastases.
  • nmCRPC (Part 2 only) defined as disease progression despite maintaining castration levels of testosterone with androgen deprivation therapy (ADT), as evidenced by an increase in consecutive prostate-specific antigen (PSA) concentrations (2 measurements, at least one week apart).
  • mCRPC (Parts 1 and 3) defined as disease progression despite maintaining castration levels of testosterone with ADT:
  • An increase in consecutive PSA (2 measurements at least 1 week apart); or
  • Worsening clinical symptoms; or
  • Radiologic evidence demonstrating enlarged metastatic lesions or the development of new metastases.
• Initiating treatment or currently receiving treatment of leuprolide acetate (3-, 4-, or 6-month injections \[intramuscular Lupron or subcutaneous Eligard\]) or another GnRH receptor agonist (triptorelin) or a GnRH receptor antagonist (degarelix or relugolix \[maximum duration of 3 months\]) in combination with:
  • Part 1: abiraterone acetate 1000 mg or fine-particle abiraterone acetate 500 mg once daily plus prednisone 5 mg once daily for participants with mCSPC or twice daily for participants with mCRPC or methylprednisolone 4 mg once daily and in whom abiraterone has been well tolerated (that is, without evidence of hepatotoxicity requiring dose adjustment for abiraterone).
  • Part 2: apalutamide 240 mg once daily and in whom apalutamide has been well tolerated (that is, without a fracture, fall, or seizure episode or need to dose adjust due to any adverse events).
  • Part 3: docetaxel 75 mg/m2 and in whom docetaxel has been well tolerated (that is, no evidence of hypersensitivity reaction, febrile neutropenia or neutrophils \< 500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or moderate neurosensory signs and/or symptoms despite dose reduction). Note: Patients receiving treatment with another agent in addition to docetaxel, such as a steroid synthesis inhibitor or androgen receptor antagonist, may be enrolled.