Relugolix vs Leuprolide for Prostate Cancer

(REPLACE-CV Trial)

Recruiting at 111 trial locations

Overseen By Clinical Trials at Myovant

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Sumitomo Pharma Switzerland GmbH

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 12 months

387 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Relugolix compared to Leuprolide for prostate cancer?

Research from the phase 3 HERO trial shows that Relugolix is more effective than Leuprolide in keeping testosterone levels low in men with advanced prostate cancer, with faster recovery of testosterone levels after stopping the drug and a lower risk of major heart-related problems. ^{1 2 3 4 5}

Is Relugolix safe compared to Leuprolide for prostate cancer treatment?

Relugolix has shown a 50% reduction in major heart-related events compared to Leuprolide in patients with advanced prostate cancer, and both treatments have been generally well tolerated in clinical trials. ^{1 3 6 7 8}

How does the drug Relugolix differ from Leuprolide in treating prostate cancer?

Relugolix is unique because it is an oral medication that provides rapid testosterone suppression without an initial surge, unlike Leuprolide, which is given as an injection. Additionally, Relugolix has been shown to reduce the risk of major adverse cardiovascular events compared to Leuprolide. ^{1 4 5 7 8}

What is the purpose of this trial?

This trial compared the safety and heart-related risks of two hormone-lowering medications, relugolix and leuprolide acetate, in adults with prostate cancer. These drugs help manage cancer by reducing testosterone levels. The study was discontinued, but patients can continue their treatment for a certain period. Relugolix is the first oral medication of its kind and was approved by the FDA based on previous study results.

Eligibility Criteria

Men over 18 with prostate cancer who need androgen deprivation therapy for at least a year can join. They should have a history of cardiovascular disease or multiple risk factors like being over 55, hypertension, high cholesterol, smoking, or family history of heart disease. Excluded are those with recent significant heart issues, uncontrolled blood pressure, long-term hormone treatments for prostate cancer (>18 months), brain metastases, or other active cancers.

Inclusion Criteria

I am eligible for both treatments offered in the study.

Has voluntarily signed and dated the informed consent form prior to baseline visit

I can think clearly enough to answer questions and participate in study activities.

Exclusion Criteria

Metastases to brain per prior clinical evaluation

My doctor plans to change my hormone therapy drugs during the study.

Treatment with any investigational product within specified timeframes

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either relugolix or leuprolide acetate for prostate cancer treatment

12 months

Day 1; 3, 6, 9, and 12 months; and every 3 months thereafter

Discontinuation Phase

Actively enrolled patients may remain on study drug up to a period of 12 months ending Dec 2024

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Leuprolide Acetate
• Relugolix

Trial Overview The trial is testing the safety of two prostate cancer treatments: Relugolix and Leuprolide Acetate. It focuses on their effects on major cardiovascular events in patients receiving these drugs as part of their treatment plan.

Participant Groups

Group I: Relugolix Experimental Treatment 1 Intervention

Oral relugolix 120 mg once daily with a loading dose of 360 mg on Day 1

Group II: Leuprolide Acetate Active Control 1 Intervention

Subcutaneous or intramuscular leuprolide acetate 22.5 mg 3-M depot or 45 mg 6-M injection or Leuprolide acetate injectable emulsion (42 mg injectable emulsion is not allowed)

Leuprolide Acetate is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Eligard for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in European Union as Lupron Depot for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Canada as Lupron for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Approved in Japan as Leuprolide Acetate for:

• Prostate cancer
• Endometriosis
• Uterine fibroids
• Precocious puberty

Who Is Running the Clinical Trial?

Sumitomo Pharma Switzerland GmbH

Lead Sponsor

Trials

19

Recruited

6,900+

Myovant Sciences GmbH

Lead Sponsor

Trials

23

Recruited

12,500+

Findings from Research

In the phase 3 HERO trial involving patients with advanced prostate cancer, relugolix showed superior sustained testosterone suppression compared to leuprolide over a 48-week period.

Relugolix also allowed for faster testosterone recovery after treatment discontinuation and was associated with a 50% reduction in major adverse cardiovascular events (MACE), highlighting its potential safety benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 3 HERO Trial Finds Relugolix to Be Superior to Leuprolide in Prostate Cancer. Slater, H.[2021]

In a study involving 1,906 patients with advanced prostate cancer, both 3-month and 6-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen (PSA) levels from an average of 12.0 ng/mL to 0.5 ng/mL after 12 months, indicating effective treatment.

The treatment was well-tolerated, with only 8.8% of patients experiencing adverse events, suggesting that leuprorelin acetate is a safe option for managing advanced prostate cancer in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. Ohlmann, CH., Gross-Langenhoff, M.[2018]

In a study of 151 men with prostate cancer, the new 6-month leuprolide acetate depot formulation achieved a 93.4% success rate in suppressing testosterone levels to ≤ 50 ng/dl, demonstrating its efficacy in hormone therapy.

The treatment was well tolerated, with sustained testosterone suppression maintained for 12 months and a significant reduction in the frequency of injections needed for patients, improving their overall treatment experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Spitz, A., Young, JM., Larsen, L., et al.[2022]

In the phase III HERO trial, relugolix demonstrated a sustained castration rate of over 90% in men with advanced prostate cancer over 48 weeks, which was non-inferior to the traditional treatment with leuprolide, and showed potential superiority in exploratory analyses.

Relugolix is generally well tolerated and may have a lower risk of major adverse cardiac events compared to leuprolide, making it a promising oral treatment option for rapid testosterone suppression without the initial surge associated with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. Shirley, M.[2023]

In the HERO study involving 930 men with advanced prostate cancer, 97% of those taking relugolix achieved sustained castration levels of testosterone compared to 89% of those receiving leuprolide, indicating relugolix is more effective in lowering testosterone levels.

Relugolix also led to a quicker reduction in testosterone levels and resulted in more men returning to normal testosterone levels after treatment, with side effects being similar and mostly mild or moderate for both treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the HERO study comparing relugolix with leuprolide for men with advanced prostate cancer. Shore, ND., Sutton, J.[2022]

In a study involving 243 prostate cancer patients, the 1- and 3-month leuprorelin acetate depot formulations significantly reduced prostate-specific antigen levels by 95% and testosterone levels by 94% after a median follow-up of 132 days, indicating strong efficacy in managing advanced prostate cancer.

The treatment was well tolerated, with 90% of physicians rating the overall safety and tolerability as good or excellent, despite 37.86% of patients experiencing some treatment-emergent adverse events, primarily related to injection sites and hot flushes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard(®)/Depo-Eligard(®)) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study. Braeckman, J., Michielsen, D.[2021]

In a study involving 1074 men with advanced prostate cancer, relugolix demonstrated similar castration resistance-free survival (CRFS) rates compared to leuprolide, with rates of 74.3% and 75.3% respectively after 48 weeks of treatment.

No new safety concerns were identified with relugolix, indicating that it is a safe alternative to leuprolide for managing advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relugolix vs. Leuprolide Effects on Castration Resistance-Free Survival from the Phase 3 HERO Study in Men with Advanced Prostate Cancer. Saad, F., George, DJ., Cookson, MS., et al.[2023]

In a 6-month study involving 117 patients with prostate cancer, the 3-month subcutaneous depot of leuprolide acetate (LA-2550) effectively suppressed serum testosterone levels to below 50 ng/dl in 98% of patients by day 28, and all patients achieved this level by day 35.

The treatment was well-tolerated, with no flare reactions and minimal adverse effects, primarily mild to moderate hot flashes, indicating a favorable safety profile while achieving significant reductions in testosterone and prostate-specific antigen levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. Chu, FM., Jayson, M., Dineen, MK., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase 3 HERO Trial Finds Relugolix to Be Superior to Leuprolide in Prostate Cancer. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Leuprorelin Acetate (Eligard®) in Daily Practice in Germany: Pooled Data from 2 Prospective, Non-Interventional Studies with 3- or 6-Month Depot Formulations in Patients with Advanced Prostate Cancer. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. [2022]

4. France pubmed.ncbi.nlm.nih.gov

Relugolix: A Review in Advanced Prostate Cancer. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Plain language summary of the HERO study comparing relugolix with leuprolide for men with advanced prostate cancer. [2022]

6. Poland pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of 1- and 3-month leuprorelin acetate depot formulations (Eligard(®)/Depo-Eligard(®)) for advanced prostate cancer in daily practice: a Belgian prospective non-interventional study. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Relugolix vs. Leuprolide Effects on Castration Resistance-Free Survival from the Phase 3 HERO Study in Men with Advanced Prostate Cancer. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A clinical study of 22.5 mg. La-2550: A new subcutaneous depot delivery system for leuprolide acetate for the treatment of prostate cancer. [2023]