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

Key Inclusion Criteria:

1. A previous diagnosis of adenocarcinoma of the prostate confirmed by histologic orcytologic evidence and with a documented medical history of either:

• mCSPC (Parts 1, 2, and 3) defined as having at least two of three risk factorsat 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 ofhepatic metastases.

• nmCRPC (Part 2 only) defined as disease progression despite maintainingcastration levels of testosterone with androgen deprivation therapy (ADT), asevidenced 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 maintainingcastration 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 thedevelopment of new metastases.

2. Initiating treatment or currently receiving treatment of leuprolide acetate (3-, 4-,or 6-month injections [intramuscular Lupron or subcutaneous Eligard]) or anotherGnRH receptor agonist (triptorelin) or a GnRH receptor antagonist (degarelix orrelugolix [maximum duration of 3 months]) in combination with:

• Part 1: abiraterone acetate 1000 mg or fine-particle abiraterone acetate 500 mgonce daily plus prednisone 5 mg once daily for participants with mCSPC or twicedaily for participants with mCRPC or methylprednisolone 4 mg once daily and inwhom abiraterone has been well tolerated (that is, without evidence ofhepatotoxicity requiring dose adjustment for abiraterone).

• Part 2: apalutamide 240 mg once daily and in whom apalutamide has been welltolerated (that is, without a fracture, fall, or seizure episode or need todose adjust due to any adverse events).

• Part 3: docetaxel 75 mg/m2 and in whom docetaxel has been well tolerated (thatis, no evidence of hypersensitivity reaction, febrile neutropenia orneutrophils < 500 cells/mm3 for more than 1 week, severe or cumulativecutaneous reactions, or moderate neurosensory signs and/or symptoms despitedose reduction). Note: Patients receiving treatment with another agent inaddition to docetaxel, such as a steroid synthesis inhibitor or androgenreceptor antagonist, may be enrolled.

Key Exclusion Criteria:

A patient will not be eligible for inclusion in the study if any of the following criteria apply:

1. A medical history of brain or hepatic metastases based on radiologic evidence or amedical history of surgical castration;

2. Received combination treatment with a GnRH analog or GnRH receptor antagonist witheither abiraterone acetate plus a corticosteroid (Part 1) or apalutamide (Part 2) inpatients with mCSPC (Part 1 and Part 2) or nmCRPC (Part 2) for a total duration > 24months or in patients with mCRPC (Part 1) for a total duration > 6 months;

3. Is scheduled or anticipates being scheduled for major surgery during the studytreatment period;

4. A current diagnosis of a malignancy other than prostate cancer, with the exceptionof 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 beenin remission for ≥ 2 years;

• Any other cancer from which the patient has been disease-free for ≥ 3 years;

5. Abnormal clinical laboratory test value(s) at the screening visit or prior to thebaseline (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/oradministration of growth factors are permitted as indicated for the clinicalmanagement of docetaxel-related hematologic effects and in accordance with theinvestigator's judgement.

6. Known hepatic disease, including alcoholic liver disease or viral hepatitis such ashepatitis A (hepatitis A virus IgM positive), chronic hepatitis B (HbsAg positive),or chronic hepatitis C (HCV antibody positive, confirmed by HCV RNA) or clinicalsigns of hepatic disease such as jaundice;

7. A medical history within 6 months prior to the screening visit or a currentdiagnosis 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, orsymptomatic cerebrovascular event[s]);

• Any other significant cardiac condition (eg, pericardial effusion, restrictivecardiomyopathy, severe untreated valvular stenosis, or severe congenital heartdisease);

8. An abnormal ECG;

9. Uncontrolled hypertension;

10. Hypotension;

11. Bradycardia;

12. Positive HIV;

13. Medical history of a bleeding disorder or current clinical evidence ofgastrointestinal bleeding or active bleeding from another anatomical location;

14. A medical history within 1 year of the screening visit of drug or alcohol abusedisorder according to Diagnostic and Statistical Manual of Mental Disorders V;

15. Received an investigational drug within 28 days or 5 half-lives, whichever islonger, prior to the baseline (Day 1) visit;

16. Prior use of any prohibited medication(s) and restrictive medication(s) without theappropriate washout period or use of a prohibited medication during the studytreatment period is planned;

17. A contraindication or known history of hypersensitivity to any of the studytreatments or components thereof, or has a history of drug or other allergy that, inthe opinion of the investigator or medical monitor, contraindicates studyparticipation;

18. Any other medical or psychiatric condition that, in the opinion of the investigator,would interfere with accomplishing the study objectives or the patient completingthe study;

19. Is a study site employee or is a primary family member (spouse, parent, child, orsibling) of a site employee involved in the conduct of the study.