Opevesostat for Prostate Cancer

(OMAHA-003 Trial)

Recruiting at 353 trial locations

Overseen By Toll Free Number

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Androgen deprivation therapy

Must not be taking: Anticancer mAbs, Herbal products

Disqualifiers: Gastrointestinal disorder, Diabetes, Cardio/cerebro-vascular disease, Seizure history, 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: Up to 54 months

1310 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called opevesostat (also known as MK-5684) for prostate cancer that has spread and no longer responds to hormonal therapy or certain chemotherapies. The researchers aim to determine if opevesostat helps patients live longer compared to existing treatments like abiraterone acetate or enzalutamide. The trial examines its effectiveness across different genetic profiles of the cancer. Men whose prostate cancer has worsened despite previous treatments and who have evidence of cancer spreading may be suitable candidates for this study. As a Phase 3 trial, it represents the final step before FDA approval, offering patients a chance to access potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participating. You must stop using herbal products with hormonal activity, 5-αreductase inhibitors, and certain other medications like strong CYP3A4 inducers and P-gp inhibitors at least 2-4 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 was reasonably safe in earlier studies with patients who have advanced prostate cancer. These studies found that patients generally tolerated the treatment well. While some experienced side effects, these were usually manageable and did not require stopping the treatment. This suggests that opevesostat might be safe for people, but individual reactions can vary.

The FDA has already approved abiraterone acetate and enzalutamide for treating prostate cancer, indicating established safety records. Most patients handle these medications well, although they can sometimes cause side effects like tiredness or high blood pressure.

Overall, evidence suggests that all three treatments tested in this trial have reasonable safety records based on previous research and approvals. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about opevesostat for prostate cancer because it offers a novel approach compared to current treatments. Unlike standard options like abiraterone acetate or enzalutamide, which focus on hormone pathways, opevesostat works by potentially targeting different biological mechanisms involved in cancer progression. Additionally, the combination with dexamethasone and fludrocortisone acetate might enhance its effectiveness, offering a fresh perspective in managing prostate cancer. This unique mechanism of action could lead to new possibilities for patients, particularly those who have not responded well to existing 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, may help treat advanced prostate cancer that no longer responds to hormone therapy. In earlier studies, opevesostat significantly lowered levels of prostate-specific antigen (PSA), an indicator of cancer activity. Specifically, 53% of patients with a certain genetic makeup saw their PSA levels drop by at least half. Even among those without this genetic makeup, about 15% experienced similar benefits. In this trial, participants will receive opevesostat as part of one treatment arm, offering a potential new option for reducing cancer activity in these 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 resisted treatment, including hormone therapy and up to two chemo treatments. Participants must have a specific performance status, which measures how well they can do daily activities, and cannot have small cell prostate cancer histology.

Inclusion Criteria

My prostate cancer is confirmed without being a small cell type.

My prostate cancer got worse while on hormone therapy or after surgery to remove my testicles, within the last 6 months.

My cancer has spread, as shown by bone scan or CT/MRI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive opevesostat or alternative NHA until progression

Up to 54 months

Regular visits as per protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 54 months

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The study compares MK-5684 to other medications like abiraterone acetate or enzalutamide in improving survival without cancer progression. It's open-label, meaning everyone knows what treatment they're getting, and it uses imaging reviews by experts who don't know the patients' group assignments.

How Is the Trial Designed?

Group I: Opevesostat Experimental Treatment 4 Interventions

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

Group II: Abiraterone Acetate or Enzalutamide Active Control 3 Interventions

Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets.

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]

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]

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 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 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]

Abiraterone acetate (Zytiga®) is an effective antiandrogen for prostate cancer but has poor oral bioavailability (<10%) and requires patients to fast around its administration due to a significant food effect (5-10-fold increase in absorption).

The review highlights the need for improved oral formulation strategies to enhance solubility and bioavailability of abiraterone acetate, aiming to reduce the required dose and eliminate the food effect, which could lead to better patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. Schultz, HB., Meola, TR., Thomas, N., et al.[2020]

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 ...