A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)

NCT06104449 | Completed Phase 1

• 3 other identifiers: 5684-005MK-5684-005jRCT2031230431
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to assess the efficacy and safety of opevesostat in the treatment of Japanese men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Next Generation Hormonal Agent (NHA) and taxane-based chemotherapy.

Conditions

Metastatic Castration-Resistant Prostate Cancer; Prostatic Neoplasms

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experience a Dose-limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 by the Investigator

  The following events, if considered drug related by the Investigator, will be considered a DLT: Grade 4 hematologic toxicity lasting ≥7 days, except anemia and thrombocytopenia; Grade 3 nausea, vomiting, diarrhea or fatigue lasting \>3 days despite optimal supportive care; other nonhematologic grade ≥3 toxicities of any duration (not laboratory); Grade ≥3 nonhematologic laboratory abnormality (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; missing \>25% of opevesostat doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.

  Up to 28 days

• Number of Participants Who Experience an Adverse Event (AE)

  An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality.

  Up to approximately 24 months

• Number of Participants Who Discontinue Study Intervention Due to an AE

  An AE is defined as any untoward medical occurrence associated with the use of a drug in a participant, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product and does not imply any judgment about causality.

  Up to approximately 24 months

Secondary Outcomes (13)

• Maximum Plasma Concentration (Cmax) of opevesostat

  Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)

• Time to Maximum Plasma Concentration (Tmax) of opevesostat

  Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)

• Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat

  Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)

• Apparent Volume of Distribution (Vz/F) of opevesostat

  Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)

• Oral Clearance (CL/F) of opevesostat

  Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)

Study Arms (1)

Opevesostat

EXPERIMENTAL

Participants receive opevesostat 5 mg by oral tablets twice daily plus dexamethasone 1.5 mg by oral tablets and fludrocortisone acetate 0.1 mg oral tablet once daily continuously until progression. Hydrocortisone up to 100 mg oral dose will also be provided to participants for use as rescue medication.

Drug: Opevesostat; Drug: Dexamethasone; Drug: Fludrocortisone acetate; Drug: Hydrocortisone

Interventions

Opevesostat DRUG

Tablets to be taken orally.

Also known as: MK-5684

Opevesostat

Dexamethasone DRUG

Tablets to be taken orally.

Also known as: Decadron

Opevesostat

Fludrocortisone acetate DRUG

Tablet to be taken orally.

Opevesostat

Hydrocortisone DRUG

Tablets to be taken orally as a recue medication.

Opevesostat

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
• Has current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
• Has ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<1.7 nmol/L)
• Participants receiving bone anti-resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to the start of study intervention.
• Has progressed on or after treatment with at least 1 line of NHAs in metastatic hormone-sensitive prostate cancer (mHSPC) or in castration-resistant prostate cancer (CRPC) for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide), and with at least 1 line of taxane-based chemotherapy in mHSPC or in CRPC, or ineligibility for chemotherapy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to allocation
• If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom.
• Has a history of pituitary dysfunction
• Has brain metastases
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
• Has an active or uncontrolled autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
• Has an active infection or other medical condition that would make corticosteroid contraindicated
• Has serious persistent infection within 2 weeks prior to the start of the study intervention
• Participants on an unstable dose of thyroid hormone therapy within 6 months prior to the start of the study intervention
• Has poorly controlled diabetes mellitus

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (3)

National Cancer Center Hospital East ( Site 0001)

Kashiwa, Chiba, 277-8577, Japan

Location

Toho University Sakura Medical Center ( Site 0003)

Sakura, Chiba, 285-8741, Japan

Location

Yokohama City University Medical Center ( Site 0002)

Yokohama, Kanagawa, 232-0024, Japan

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dexamethasone; Calcium Dobesilate; fludrocortisone acetate; Hydrocortisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2023
• First Posted: October 27, 2023
• Study Start: November 14, 2023
• Primary Completion: February 20, 2026
• Study Completion: April 17, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

JP (3)