A Study of Opevesostat (MK-5684) in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001)

NCT06136598 | Completed Phase 1

• 2 other identifiers: 5684-001MK-5684-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

The primary objectives of this study are to evaluate the safety and tolerability of opevesostat in the treatment of male Chinese participants with metastatic castration-resistant prostate cancer (mCRPC) and to characterize the pharmacokinetic profile of opevesostat. There are no formal hypotheses to be tested in this study.

Conditions

Prostatic Neoplasms; Metastatic Castration-Resistant Prostate Cancer

Outcome Measures

Primary Outcomes (8)

• 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 20 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 20 months

• Maximum Plasma Concentration (Cmax) of opevesostat

  Blood samples will be collected at pre-specified timepoints to determine the Cmax of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

• Time to Maximum Plasma Concentration (Tmax) of opevesostat

  Blood samples will be collected at pre-specified timepoints to determine the Tmax of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

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

  Blood samples will be collected at pre-specified timepoints to determine the AUC0-12 of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

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

  Blood samples will be collected at pre-specified timepoints to determine the Vz/F of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

• Oral Clearance (CL/F) of opevesostat

  Blood samples will be collected at pre-specified timepoints to determine the CL/F of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

• Half-Life (t1/2) of opevesostat

  Blood samples will be collected at pre-specified timepoints to determine the t1/2 of opevesostat.

  Day 1 and Day 8: predose and 0.5, 1, 2, 3, 4, 6, 9, and 12 hours postdose, Day 29, Day 57, and Day 89: pre-dose

Secondary Outcomes (6)

• Prostate-specific Antigen (PSA) Response Rate

  Up to approximately 37 months

• Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 37 months

• Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1

  Up to approximately 37 months

• Duration of Response (DOR) Per PCWG-modified RECIST 1.1

  Up to approximately 37 months

• Overall Survival (OS)

  Up to approximately 37 months

Study Arms (1)

Opevesostat

EXPERIMENTAL

Participants will receive opevesostat by oral tablets twice daily plus dexamethasone and fludrocortisone by oral tablets once daily continuously until unacceptable toxicity or documented progression. Hydrocortisone will also be provided to participants for use as rescue medication.

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

Opevesostat

Fludrocortisone DRUG

Tablets to be taken orally.

Also known as: Fludrocortisone acetate

Opevesostat

Hydrocortisone DRUG

Tablet to be taken orally as a rescue medication.

Also known as: Hydrocortisone acetate

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 prostate cancer while receiving androgen deprivation therapy (ADT), or post-bilateral orchiectomy, within 6 months before screening.
• Has evidence of progression \>4 weeks since last flutamide treatment or \>6 weeks since last bicalutamide or nilutamide treatment.
• Has evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue shown by CT/MRI.
• Has disease that progressed during or after treatment with at least 1 line of next-generation hormonal agents (NHAs) for hormone-sensitive prostate cancer (HSPC) or castration-resistant prostate cancer (CRPC) for at least 8 weeks (at least 14 weeks for participants with bone progression).
• Has received at least 1 line of taxane-based chemotherapy for HSPC or CRPC and have had progressed disease during or on treatment, or refused or ineligible to receive chemotherapy.
• Has a life expectancy of \>3 months.
• Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.
• Has presence of gastrointestinal condition, e.g. malabsorption, that might affect the adsorption of study intervention.
• Has a history of pituitary dysfunction.
• Has poorly controlled diabetes mellitus.
• Has active or unstable cardio/cerebro-vascular disease, including thromboembolic events.
• Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 4 weeks of the date of allocation.
• Has received an anticancer monoclonal antibody (mAb) within 4 weeks of allocation, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of allocation.
• Received prior systemic anticancer therapy including investigational agents within 4 weeks before the date of allocation.

Sponsors & Collaborators

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

Study Sites (3)

Peking University First Hospital-Urology ( Site 0001)

Beijing, Beijing Municipality, 100034, China

Location

Sun Yat-sen University Cancer Center-Neurosurgery department ( Site 0003)

Guangzhou, Guangdong, 510700, China

Location

Tongji Hospital Tongji Medical,Science & Technology ( Site 0002)

Wuhan, Hubei, 430000, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Dexamethasone; dexamethasone acetate; Fludrocortisone; fludrocortisone acetate; Hydrocortisone; hydrocortisone acetate

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; 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: November 13, 2023
• First Posted: November 18, 2023
• Study Start: January 30, 2024
• Primary Completion: March 9, 2026
• Study Completion: March 9, 2026
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (3)