Opevesostat + Hormone Therapy for Prostate Cancer

Recruiting at 405 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Hormone replacement therapy

Must not be taking: CYP450-inducing antiepileptics, CYP3A4 inducers

Disqualifiers: Gastrointestinal condition, Diabetes, Cardio/cerebro-vascular, others

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: Unknown

Duration: Until disease progression

1314 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for prostate cancer that has spread and no longer responds to standard hormone therapy. Researchers aim to determine if the new drug, opevesostat (also known as MK-5684), is more effective with hormone therapy than existing drugs like abiraterone or enzalutamide. The trial examines how long patients can live without their cancer worsening. It may suit men whose prostate cancer has progressed despite hormone therapy and who show evidence of cancer spread. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, it mentions that participants should not have received certain treatments like taxane-based chemotherapy or NHAs for mCRPC recently, and there are restrictions on using certain drugs like strong CYP3A4 inducers and P-gp inhibitors within 2 weeks before starting the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that opevesostat is generally safe. In studies, patients with advanced prostate cancer who had already tried other treatments tolerated it well. While taking opevesostat, some common side effects occurred, but they were usually manageable.

Alternative treatments, abiraterone acetate and enzalutamide, have received FDA approval for prostate cancer, indicating well-documented safety in humans. People taking these medications might experience side effects, but these are usually well-understood and manageable.

Overall, these treatments offer a promising balance between effectiveness and safety for people with advanced prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Opevesostat is unique because it works by specifically targeting and inhibiting a key enzyme involved in cancer cell metabolism, setting it apart from traditional hormone therapies like abiraterone and enzalutamide. This enzyme inhibition could potentially result in a more effective way to slow down or stop prostate cancer progression. Researchers are excited about Opevesostat because it offers a novel mechanism of action that could enhance treatment outcomes for patients who may not respond adequately to existing hormonal therapies.

What evidence suggests that this trial's treatments could be effective for metastatic castration-resistant prostate cancer?

Research has shown that opevesostat, also known as MK-5684, holds promise for treating advanced prostate cancer that no longer responds to hormone therapy. Studies have found it significantly lowers PSA levels, markers for prostate cancer. Specifically, about 53% of patients experienced a 50% reduction in PSA levels with opevesostat treatment. In this trial, one group of participants will receive opevesostat combined with hormone replacement therapy.

Another group will receive treatments like abiraterone acetate and enzalutamide, which are already used for this type of cancer and work by targeting hormones to control it. Both approaches in this trial aim to manage cancer growth and help patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that has spread and worsened despite hormone therapy. They must have tried one hormonal drug already, be in good physical shape (able to perform daily activities), and have normal organ function. Men who've had small cell prostate cancer or more than six cycles of a specific chemotherapy aren't eligible.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My prostate cancer is confirmed and not of the small cell type.

My organs are functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive opevesostat plus hormone replacement therapy or alternative abiraterone acetate or enzalutamide until disease progression

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 82 months

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone acetate
• Dexamethasone
• Enzalutamide
• Fludrocortisone acetate
• Hydrocortisone
• MK-5684
• Prednisone acetate

Trial Overview The study compares MK-5684 plus hormone replacement against other drugs like abiraterone acetate or enzalutamide in controlling advanced prostate cancer. It measures how long patients live without their disease getting worse on scans and overall survival, especially focusing on those with certain genetic features of the cancer.

How Is the Trial Designed?

Group I: Hormone Replacement Therapy (HRT) + Opevesostat Experimental Treatment 4 Interventions

Participants receive opevesostat 5 mg by oral tablets twice daily (BID) plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily (QD) continuously until disease progression. Hydrocortisone 100 mg (oral or intramuscular \[IM\]) will also be provided to participants for use as rescue medication.

Group II: Alternative Next-Generation Hormonal Agent (NHA) Active Control 3 Interventions

Participants receive abiraterone 1000mg QD by oral tablets plus prednisone 5 mg BID by oral tablets or enzalutamide 160 mg QD by oral tablets until disease progression.

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

Approved in European Union as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in United States as Zytiga for:

• Metastatic castration-resistant prostate cancer
• High-risk metastatic hormone-sensitive prostate cancer

Approved in Canada as Zytiga for:

• Metastatic castration-resistant prostate cancer

Approved in Japan as Zytiga for:

• Metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Orion Corporation, Orion Pharma

Industry Sponsor

Trials

140

Recruited

45,200+

Liisa Hurme

Orion Corporation, Orion Pharma

Chief Executive Officer since 2022

PhD in Biochemistry, University of Helsinki

Hilpi Rautelin

Orion Corporation, Orion Pharma

Chief Medical Officer since 2023

MD, University of Turku

Published Research Related to This Trial

A study involving 32 healthy male subjects demonstrated that the test product (abiraterone acetate tablet) is bioequivalent to the reference product ZYTIGA® in terms of pharmacokinetics, with both products showing similar maximum concentration (Cmax) and area under the curve (AUC) values within the acceptable range.

The research confirmed significant intra-subject variability in the pharmacokinetics of abiraterone, indicating that individual responses to the drug can vary widely, which is important for clinicians to consider when prescribing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of generic and branded abiraterone acetate tablet: a single-dose, open-label, and replicate designed study in healthy Chinese male volunteers. Wang, C., Hu, C., Gao, D., et al.[2022]

Men with advanced prostate cancer taking abiraterone have a significantly higher risk of major metabolic or cardiovascular adverse events compared to those not on the medication, with a hazard ratio of 1.77.

Enzalutamide also increases the risk of major adverse events, but to a lesser extent (hazard ratio of 1.22), and does not significantly increase the risk of minor adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. Lai, LY., Oerline, MK., Caram, MEV., et al.[2023]

In a study of 38 patients with metastatic castration-resistant prostate cancer (mCRPC) who had previously been treated with docetaxel and enzalutamide, abiraterone and prednisolone showed modest antitumor activity, with only 8% of patients achieving a significant PSA response.

The treatment was well tolerated, but the median progression-free survival was only 2.7 months, indicating limited effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). Loriot, Y., Bianchini, D., Ileana, E., et al.[2023]

In a study involving 1919 patients with metastatic prostate cancer, the addition of abiraterone acetate to standard androgen deprivation therapy significantly improved overall survival, with a median survival of 76.6 months compared to 45.7 months for standard care alone.

Combining both abiraterone and enzalutamide did not provide additional survival benefits over abiraterone alone, and it was associated with higher rates of severe side effects, suggesting that this combination should be avoided in long-term treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Attard, G., Murphy, L., Clarke, NW., et al.[2023]

Enzalutamide is an effective androgen receptor inhibitor that improves overall survival in patients with metastatic castration-resistant prostate cancer, showing a 4.8-month survival benefit in those previously treated with docetaxel, as demonstrated in the Phase III AFFIRM trial.

The FDA has expanded enzalutamide's approval to include first-line treatment for metastatic castration-resistant prostate cancer in patients who have not yet received chemotherapy, and it is associated with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. Ramadan, WH., Kabbara, WK., Al Basiouni Al Masri, HS.[2020]

Oral abiraterone acetate (Zytiga®) significantly improves overall survival and progression-free survival in patients with metastatic castration-resistant prostate cancer (CRPC) when used with prednisone, compared to a placebo.

The treatment is specifically effective for patients who have already undergone docetaxel-containing chemotherapy, highlighting its role as a subsequent therapy in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. Scott, LJ., Yang, LPH., Lyseng-Williamson, KA.[2021]

In a study of 61 men with metastatic, castration-resistant prostate cancer who had previously received docetaxel and abiraterone acetate, enzalutamide showed modest clinical activity, with 21% of patients experiencing a significant PSA decline of 50% or more.

The median overall survival for patients treated with enzalutamide was 31.6 weeks, and the treatment was generally well tolerated, although fatigue and musculoskeletal pain were common side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical activity and tolerability of enzalutamide (MDV3100) in patients with metastatic, castration-resistant prostate cancer who progress after docetaxel and abiraterone treatment. Badrising, S., van der Noort, V., van Oort, IM., et al.[2022]

In a study of 3,398 patients with metastatic castration-resistant prostate cancer, those initiated on abiraterone acetate (AA) had a significantly longer duration of treatment compared to those initiated on enzalutamide (ENZ), with a median duration of 18.3 months for AA versus 14.2 months for ENZ.

Patients on AA also experienced fewer treatment discontinuations at various time points, indicating that AA may provide a more sustained treatment option for managing prostate cancer compared to ENZ.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Prostate Cancer Patients Treated with Abiraterone Acetate or Enzalutamide. Pilon, D., Behl, AS., Ellis, LA., et al.[2023]

The use of abiraterone and enzalutamide, oral therapies for metastatic castration-resistant prostate cancer, has significantly increased among urologists from 2013 to 2016, with abiraterone prescriptions rising from 71,423 to 100,371 and enzalutamide from 29,572 to 100,980.

The number of urologists prescribing these medications in moderate to high volumes grew substantially, indicating a shift in treatment practices, with 301 urologists prescribing abiraterone and 671 prescribing enzalutamide by 2016, primarily within single-specialty groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoption of Abiraterone and Enzalutamide by Urologists. Caram, MEV., Kaufman, SR., Modi, PK., et al.[2021]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.159

MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with ... MK-5684 profoundly suppressed androgen synthesis resulting in PSA50 responses in 55.6% and 16.7% of patients and PSA30 responses in 69.8% and ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03205-8/fulltext

1605P Opevesostat (MK-5684/ODM-208), an oral ... Opevesostat treatment led to PSA50 responses in 53.0% and 14.7% of patients, and PSA30 responses in 68.2% and 29.4% of patients, with and without AR-LBD ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT437212

MK-5684 (ODM-208), a CYP11A1 inhibitor, in patients with ... MK-5684 profoundly suppressed androgen synthesis resulting in PSA50 responses in 55.6% and 16.7% of patients and PSA30 responses in 69.8% and 30.0% of patients, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10852404/

Targeted Inhibition of CYP11A1 in Castration-Resistant ... The CYPIDES study (NCT03436485) was conducted to evaluate the safety and preliminary efficacy of ODM-208 in pretreated patients with metastatic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06353386

Study Details | NCT06353386 | Substudy 01A: Safety and ... The goal of substudy 01A is to evaluate the safety and efficacy of opevesostat-based treatment combinations, or as a single agent, in participants with mCRPC.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03436485

NCT03436485 | Safety and Pharmacokinetics of ODM-208 ... The purpose of this first-in-man study is to evaluate safety and tolerability of ODM-208 in patients with metastatic castration-resistant prostate cancer.

7. urotoday.com urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154774-esmo-2024-opevesostat-mk-5684-odm-208-an-oral-cyp11a1-inhibitor-in-metastatic-castration-resistant-prostate-cancer-mcrpc-updated-cypides-phase-2-results.html

ESMO 2024: Opevesostat (MK-5684/ODM-208), an Oral ... Initial phase I and II results demonstrated frequent PSA responses in heavily pre-treated mCRPC patients, especially in the presence of ...