Opevesostat for Prostate Cancer

Recruiting at 293 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

1200 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) and to radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria In Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS and rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

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.

What data supports the effectiveness of the drug Opevesostat for prostate cancer?

Research shows that abiraterone acetate, often used with prednisone, improves survival in patients with metastatic castration-resistant prostate cancer. Additionally, combining abiraterone with enzalutamide and androgen deprivation therapy has been shown to improve outcomes for these patients. ^{1 2 3 4 5}

Is Opevesostat safe for humans?

Abiraterone acetate, a component of Opevesostat, has been used safely in combination with other drugs for treating prostate cancer, but it may increase the risk of metabolic (related to the body's chemical processes) and cardiovascular (heart and blood vessel) issues. ^{1 2 5 6 7}

What makes the drug Opevesostat for prostate cancer unique?

Opevesostat, combined with Abiraterone acetate and Enzalutamide, offers a novel approach by potentially enhancing the effectiveness of existing prostate cancer treatments. This combination targets different pathways involved in cancer progression, which may improve outcomes compared to using these drugs individually. ^{1 2 5 8 9}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

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]

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]

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]

References

1. England 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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Abiraterone acetate: a guide to its use in metastatic castration-resistant prostate cancer. [2021]

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

Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100). [2023]

4. United States 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. [2022]

5. Germany 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. [2022]

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

Risk of Metabolic and Cardiovascular Adverse Events With Abiraterone or Enzalutamide Among Men With Advanced Prostate Cancer. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Enzalutamide for patients with metastatic castration-resistant prostate cancer. [2020]

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

Adoption of Abiraterone and Enzalutamide by Urologists. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Oral formulation strategies to improve the bioavailability and mitigate the food effect of abiraterone acetate. [2020]