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 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.

2. 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.

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 a
medical history of surgical castration;

2. 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;

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

4. 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;

5. 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.

6. 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;

7. 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);

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 of
gastrointestinal bleeding or active bleeding from another anatomical location;

14. 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;

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

16. 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;

17. 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;

18. 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;

19. 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.