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

Myovant Sciences GmbH1,134 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

1,134

Conditions

Prostate Cancer

Interventions

RelugolixDRUG

Relugolix 120-mg tablet administered orally once daily following an oral loading dose of 360 mg (3 x 120-mg tablets) on Day 1

Leuprolide AcetateDRUG

Leuprolide acetate depot suspension, 22.5 mg (or 11.25 mg in Japan, Taiwan, and China), every 3 months by subcutaneous injection

Eligibility

Sex: MALEMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (162)

Outcomes

Primary Outcomes

Sustained Castration Rate

Sustained castration rate defined as the cumulative probability of testosterone suppression to \< 50 nanogram (ng)/deciliter (dL). The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants. The lower bound of the 95% confidence interval (CI) for the cumulative probability of sustained testosterone suppression in the relugolix treatment group must have been ≥ 90% to meet evaluation criteria for efficacy.

Time frame: From Week 5 Day 1 (Day 29) to Week 49 Day 1 (Day 337)

Secondary Outcomes

Castration Rate At Week 1 Day 4

Castration rate was defined as the cumulative probability of testosterone suppression to \< 50 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 1 Day 4 (Day 4)

Castration Rate At Week 3 Day 1

Time frame: Week 3 Day 1 (Day 15)

Confirmed Prostate-specific Antigen (PSA) Response Rate

Confirmed PSA response defined as \> 50% reduction in PSA from baseline at Week 3 Day 1 followed with confirmation at Week 5 Day 1.

Time frame: Week 3 Day 1 (Day 15) and Week 5 Day 1 (Day 29)

Profound Castration Rate At Week 3 Day 1 (Day 15)

Castration rate defined as the cumulative probability of testosterone suppression to \< 20 ng/dL. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 3 Day 1 (Day 15)

Data from ClinicalTrials.gov

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Tucson

Tucson, Arizona, United States

Orange

Orange, California, United States

Denver

Denver, Colorado, United States

Pompano Beach

Pompano Beach, Florida, United States

Jeffersonville

Jeffersonville, Indiana, United States

Des Moines

Des Moines, Iowa, United States

Wichita

Wichita, Kansas, United States

Baltimore

Baltimore, Maryland, United States

Troy

Troy, Michigan, United States

Omaha

Omaha, Nebraska, United States

...and 152 more locations

Follicle-stimulating Hormone (FSH) Level

To evaluate the effect of relugolix and leuprolide acetate on FSH suppression.

Time frame: Week 25 Day 1 (Day 169)

PSA Response Rate At Week 3 Day 1

PSA response defined as \> 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 3 Day 1 (Day 15)

PSA Response Rate At Week 5 Day 1

PSA response defined as \> 50% reduction in PSA from baseline. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 5 Day 1 (Day 29)

Testosterone Recovery Rate

The cumulative probability of testosterone recovery back to \> 280 ng/dL (lower limit of the normal range), back to ≥ 50 ng/dL (definition of castration), and back to \> 280 ng/dL or baseline at 90 days after drug discontinuation was assessed. The rate was estimated for each treatment group using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Day 90 follow-up

Sustained Profound Castration Rate From Week 5 Day 1 Through Week 49 Day 1

Sustained profound castration rate was defined as the cumulative probability of testosterone suppression to \< 20 ng/dL. The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 5 Day 1 (Day 29) through Week 49 Day 1 (Day 337)

Profound Castration Rate At Week 1 Day 4 (Day 4)

Time frame: At Week 1 Day 4 (Day 4)

Sustained Profound Castration Rate From Week 25 Day 1 Through Week 49 Day 1

Time frame: Week 25 Day 1 (Day 169) through Week 49 Day 1 (Day 337)

Undetectable PSA Rate

Defined as the proportion of participants with PSA concentration \< 0.02 ng/milliliter (mL).The rate was estimated by the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 25 Day 1 (Day 169)

Rate Of PSA Progression-free Survival

PSA progression was defined as the first increase in PSA of 25% or greater and 2 ng/mL or greater above the nadir with confirmation by a second consecutive PSA measurement at least 3 weeks later. For participants without declining PSA from baseline, a PSA increase of ≥ 25% and ≥ 2 ng/mL from baseline beyond 12 weeks was considered PSA progression. The rate of progression-free survival was estimated using the Kaplan-Meier method and reported as percentage of participants.

Time frame: Week 49 Day 1 (Day 337)

Change From Baseline In Quality Of Life (QoL) Total Score As Assessed By The Global Health Domain Of The European Organisation Of Research And Treatment Of Cancer (EORTC)-Quality Of Life Questionnaire (QLQ)-C30

The EORTC QLQ-C30 core measurement was used to capture distal outcomes, including physical, social functioning, and overall health-related quality of life. The questionnaire incorporates 30 questions comprising nine multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and quality of life scale. All raw domain scores are linearly transformed to a 0-100 scale. The global health and quality of life domain is presented. An increase in activity or functioning scores indicates improvement (higher/healthier level of functioning) and a decrease in symptom scores indicates improvement (lower level of symptoms/problems).