Skip to main content
UK clinical trials - updated daily from ClinicalTrials.gov
TrialConnect
← Back to Search
Looking for participantsPhase3

A Study of Opevesostat (MK-5684) Versus Alternative Next-generation Hormonal Agent (NHA) in Metastatic Castration-resistant Prostate Cancer (mCRPC) Post One NHA (MK-5684-004)

Sponsor: Merck Sharp & Dohme LLC

NCT ID: NCT06136650

View on ClinicalTrials.gov ↗

At a glance

What the study gets you
Access to the study treatment being tested
Type of study
Interventional (receives a drug or procedure)
Time in hospital
In-person visits at study sites — visit count not specified by the sponsor
Drug or intervention
Opevesostat (drug), Dexamethasone (drug), Fludrocortisone acetate (drug), Hydrocortisone (drug)
How long the study runs
Study runs about 84 months (dates as stated)
About the drug or intervention
Opevesostat — drug: Administered orally · Dexamethasone — drug: Administered orally · Fludrocortisone acetate — drug: Administered orally · Hydrocortisone — drug: Administered orally or IM as a rescue drug · Abiraterone acetate — drug: Administered orally · Prednisone acetate — drug: Administered orally · Enzalutamide — drug: Administered orally
Patient visit burden
Not specified by the sponsor
Type of study
Testing a treatment
Ages
18 Years and over
Who
All
Number of participants
1,314
Started
2023-12-18
Last checked
2026-10

Plain English Summary

What is this study?

  • • Testing a new treatment for metastatic castration-resistant prostate cancer (mcrpc)
  • • Phase3 - 1,314 participants
  • • The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA)

Who can take part?

  • • Ages 18 Years and over
  • • Diagnosed with metastatic castration-resistant prostate cancer (mcrpc)

Where?

  • • Cambridge - Addenbrooke's Hospital ( Site 1426)
  • • Derby - Royal Derby Hospital ( Site 1431)
  • • Torquay - Torbay Hospital ( Site 1429)
  • • Northwood - Mount Vernon Cancer Centre ( Site 1440)
  • • +9 more UK sites

This is a simplified summary. Always discuss with your doctor before making any decisions.

About This Trial

The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypothesis is that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to overall survival (OS), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.

More detail

Per Protocol Amendment 08, OS was moved to be a secondary outcome measure. Per Protocol Amendment 11, OS was returned to a primary outcome measure.

Metastatic Castration-resistant Prostate Cancer (mCRPC)Prostatic Neoplasms

How this trial compares with your answers

Answer 2 more questions to improve match

What we know so far

Condition· Matched your search
Age· Tell us your age for better matching
Gender· Tell us your sex for better matching

Still need:

  • • Tell us your age for better matching
  • • Tell us your sex for better matching

Preliminary match based on your answers. Full eligibility requires on-site assessment including medical history, physical exam, and lab tests. This does not guarantee enrolment.

Eligibility at a Glance

Key info

  • Age: 18 Years and over
  • Who can join: All genders

Treatment history

Treatments you must have had:

  • ✓ poly (ADP-ribose) polymerase inhibit
  • ✓ recovered to ≤Grade 1 or baseline
  • ✓ well controlled HIV on antiretroviral therapy (ART)

What the study is looking for

  • ✓The main inclusion criteria include but are not limited to the following:
  • ✓Have confirmed by testing a sample adenocarcinoma of the prostate without small cell histology
  • ✓Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy)...
  • ✓Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive...
  • ✓Has ongoing androgen deprivation therapy (ADT) with serum testosterone \<50 ng/dL (\<1.7 nM)

Who cannot take part

  • ✗The main exclusion criteria include but are not limited to the following:
  • ✗Has presence of gastrointestinal condition
  • ✗Is unable to swallow capsules/tablets
  • ✗Has history of pituitary dysfunction
  • ✗Has poorly controlled diabetes mellitus
See the full criteria
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Have histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology * Has prostate cancer progression while receiving androgen deprivation therapy (ADT) (or post bilateral orchiectomy) within 6 months before screening * Has current evidence of distant metastatic disease (M1 disease) documented by either bone lesions on bone scan and/or soft tissue disease shown by computed tomography (CT)/magnetic resonance imaging (MRI) * Has disease that progressed during or after treatment with one next-generation hormonal agent (NHA) for hormone sensitive prostate cancer (HSPC) (metastatic hormone-sensitive prostate cancer \[mHSPC\] or non-metastatic hormone-sensitive prostate cancer \[nmHSPC\]), or castration-resistant prostate cancer (CRPC) (metastatic castration-resistant prostate cancer \[mCRPC\] or non-metastatic castration-resistant prostate cancer \[nmCRPC\]), for at least 8 weeks of NHA treatment (at least 14 weeks of NHA treatment for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel * Has had prior treatment with poly (ADP-ribose) polymerase inhibitor (PARPi) or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment * Has ongoing androgen deprivation therapy (ADT) with serum testosterone \<50 ng/dL (\<1.7 nM) * Has an eastern clinical oncology group (ECOG) performance status of 0 or 1 assessed within 10 days before randomization * Has adequate organ function * Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening * Participants who have adverse event (AEs) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy or ≤Grade 2 osteopenia/osteoporosis are eligible * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has presence of gastrointestinal condition * Is unable to swallow capsules/tablets * Has history of pituitary dysfunction * Has poorly controlled diabetes mellitus * Has clinically significant abnormal serum potassium or sodium level * Has any of the following at screening visit: Hypotension: systolic blood pressure (BP) \<110 mmHg, or uncontrolled hypertension: systolic BP ≥160mmHg or diastolic blood BP ≥90 mmHg, in 2 out of the 3 recordings with optimized antihypertensive therapy * Has a history of active or unstable cardio/cerebrovascular disease, including thromboembolic events * History or family history of long QTc syndrome * Has a history of seizure(s) within 6 months before providing documented informed consent (IC) or has any condition that may predispose to seizure within 12 months prior to the date of enrollment * Has a history of clinically significant ventricular arrhythmias or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place * Has received a taxane-based chemotherapy for metastatic castration-resistant prostate cancer (mCRPC) * Has not adequately recovered from major surgery or have ongoing surgical complications * Is currently being treated with Cytochrome P450 (CYP450)-inducing antiepileptic drugs for seizures * Participants on an unstable dose of thyroid hormone therapy, as judged by the investigator, within 6 months before the start of the study intervention * Receives prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids * Receives prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention * Has systemic use of strong Cytochrome P450 3A4 (CYP3A4) inducers and P-glycoprotein (P-gp) inhibitors within 2 weeks before the first dose of study intervention * Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention * Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or opevesostat * Has a "superscan" bone scan defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention * Has active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is allowed * Active infection requiring systemic therapy * Has concurrent active Hepatitis B virus and Hepatitis C virus infection

Where Is This Study? (13 UK sites)

Addenbrooke's Hospital ( Site 1426)

Cambridge CB2 2QQ, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01223216083

Royal Derby Hospital ( Site 1431)

Derby DE22 3NE, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441332340131

Torbay Hospital ( Site 1429)

Torquay TQ2 7AA, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01803 656627

Mount Vernon Cancer Centre ( Site 1440)

Northwood HA6 2RN, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator0203 826 2164

The Royal Cornwall Hospital ( Site 1430)

Truro TR1 3LJ, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator01872258345

The Beatson West of Scotland Cancer Centre ( Site 1428)

Glasgow G12 0YN, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441413017000

University College London Hospital ( Site 1437)

London NW1 2PG, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator0203 447 3042

Guy's & St Thomas' NHS Foundation Trust-Oncology & Haematology Clinical Trials ( Site 1435)

London SE1 9RT, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator02071882007

St. George's Hospital-Oncology ( Site 1441)

London SW17 0QT, United Kingdom

COMPLETED
Hospital R&D contact (matched)

Mr Subhir Bedi

researchgovernance@sgul.ac.uk020 8725 4986

Charing Cross Hospital ( Site 1434)

London W6 8RF, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+4402033138335

GenesisCare - Oxford ( Site 1442)

Oxford OX4 6LB, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+447407796352

GenesisCare - Windsor ( Site 1443)

Windsor SL4 3HD, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+447879262807

The Christie NHS Foundation Trust ( Site 1436)

Manchester m20 4bx, United Kingdom

Recruiting
Site contact (verified)
Study Coordinator+441614463000

How to Get in Touch

Toll Free Number

Sponsor contact

CONTACT

1-888-577-8839 Trialsites@msd.com
Data sourced from ClinicalTrials.gov · Last verified: 2026-10