A Study to Evaluate the Safety and Efficacy of Relugolix in Men With Advanced Prostate Cancer

The purpose of this study is to determine the efficacy and safety of relugolix 120 milligrams (mg) orally once daily for 48 weeks on maintaining serum testosterone suppression to castrate levels (\< 50 nanograms/deciliter \[ng/dL\]) in participants with androgen-sensitive advanced prostate cancer.

This is a phase 3, multinational, randomized, open-label, parallel group study to evaluate the efficacy and safety of oral daily relugolix 120 mg in participants with androgen-sensitive advanced prostate cancer who require at least 1 year of continuous androgen-deprivation therapy. Relugolix 120 mg orally once daily or leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan and Taiwan based on local labels), every 3 months by subcutaneous injection will be administered to participants.

There are 2 analyses for this study, a primary analysis and a final analysis.

Primary Analysis:

The primary analysis of efficacy and safety has been completed (N=934). Participants were randomized 2:1 to receive relugolix or leuprolide for 48 weeks, followed by a 30-day safety follow-up visit or early termination 30-day safety follow-up.

Final Analysis:

The final analysis will occur after additional participants with metastatic disease (approximately 130) have been enrolled and randomized from any sites to the study, and have completed the 48-week treatment period. A cohort of participants enrolled in China and Taiwan will be analyzed separately once they have completed treatment to support registration in China.

Eligible participants were randomized 2:1 to relugolix or leuprolide arm and will attend visits monthly (every 4 weeks) where serum testosterone and prostate-specific antigen will be assessed. Safety will be assessed throughout the study by monitoring adverse events, vital signs, physical examinations, clinical laboratory tests, and 12-lead electrocardiograms.

Castration resistance-free survival will be assessed up to Week 49, Day 1 of the study and reported as part of the final analysis.

The study enrolled 1134 participants, including 139 participants with metastatic advanced prostate cancer to support the analysis of the secondary endpoint of castration resistance-free survival and 93 Chinese participants (enrolled in China and Taiwan) to support registration in China.

Eligibility Criteria:
Key Inclusion Criteria:

1. Has histologically or cytologically confirmed diagnosis of adenocarcinoma of the prostate.
2. Is a candidate for, in the opinion of the investigator, at least 1 year of continuous androgen deprivation therapy for the management of androgen-sensitive advanced prostate cancer with 1 of the following clinical disease state presentations:

   1. Evidence of biochemical (PSA) or clinical relapse following local primary intervention with curative intent, such as surgery, radiation therapy, cryotherapy, or high-frequency ultrasound and not a candidate for salvage treatment by surgery; or
   2. Newly diagnosed androgen-sensitive metastatic disease; or
   3. Advanced localized disease unlikely to be cured by local primary intervention with either surgery or radiation with curative intent.
3. Has a serum testosterone at the Screening visit of ≥ 150 ng/dL (5.2 nanomoles \[nmol\]/liter \[L\]).
4. Has a serum PSA concentration at the Screening visit of \> 2.0 ng/milliliter (mL) (2.0 microgram \[μg\]/L), or, when applicable, post radical prostatectomy of \> 0.2 ng/mL (0.2 μg/L) or post radiotherapy, cryotherapy, or high frequency ultrasound \> 2.0 ng/mL (2.0 μg/L) above the post interventional nadir.
5. Has an Eastern Cooperative Oncology Group performance status of 0 or 1 at initial screening and at baseline.

Key Exclusion Criteria:

1. In the investigator's opinion, is likely to require chemotherapy or surgical therapy for symptomatic disease management within 2 months of initiating androgen deprivation therapy.
2. Previously received gonadotropin-releasing hormone analog or other form of androgen deprivation therapy (estrogen or antiandrogen) for \> 18 months total duration. If androgen deprivation therapy was received for ≤ 18 months total duration, then that therapy must have been completed at least 3 months prior to baseline. If the dosing interval of the depot is longer than 3 months, then the prior androgen deprivation therapy must have been completed at least as long as the dosing interval of the depot.
3. Previous systemic cytotoxic treatment for prostate cancer (for example, taxane-based regimen).
4. Metastases to brain per prior clinical evaluation.
5. Participants with myocardial infarction, unstable symptomatic ischemic heart disease, cerebrovascular events, or any significant cardiac condition within the prior 6 months.
6. Active conduction system abnormalities.
7. Uncontrolled hypertension.