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

A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Prostatic Neoplasms; Metastatic Castration-Resistant Prostate Cancer
• Intervention / Treatment: Drug: Dexamethasone; Drug: Fludrocortisone; Drug: Hydrocortisone; Drug: Opevesostat

• Study Type: Interventional
• Enrollment (Estimated): 14
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Peking University First Hospital-Urology ( Site 0001)
      • Contact: Study Coordinator; Phone Number: 8613910688432
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Recruiting
      • Tongji Hospital Tongji Medical,Science & Technology ( Site 0002)
      • Contact: Study Coordinator; Phone Number: 13971656164

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any form of immunosuppressive therapy within 7 days prior to the start of study intervention.
• Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of or current human immunodeficiency virus (HIV) infection.
• Has a concurrent Hepatitis B or Hepatitis C virus infection.
• Has a history of allogenic tissue or solid organ transplant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Opevesostat; 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: Dexamethasone; Tablets to be taken orally; Other Names: Dexamethasone acetate; Drug: Fludrocortisone; Tablets to be taken orally.; Other Names: Fludrocortisone acetate; Drug: Hydrocortisone; Tablet to be taken orally as a rescue medication.; Other Names: Hydrocortisone acetate; Drug: Opevesostat; Tablets to be taken orally.; Other Names: MK-5684

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 27 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 27 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prostate-specific Antigen (PSA) Response Rate	The PSA response rate is defined as the percentage of participants in the analysis population with a reduction in PSA level of ≥50% measured twice ≥3 weeks apart.	Up to approximately 44 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)	rPFS is defined as the time from first dose of study intervention to radiographic progression per PCWG-modified RECIST 1.1 as assessed by the investigator OR death due to any cause, whichever occurs first.	Up to approximately 44 months
Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1	ORR is defined as the percentage of participants who have a best overall response of either confirmed Complete Response (CR: disappearance of all target lesions) or a confirmed Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1 as assessed by the investigator.	Up to approximately 44 months
Duration of Response (DOR) Per PCWG-modified RECIST 1.1	For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1, DOR is defined as the time from first documented evidence of confirmed CR or PR until disease progression or death from any cause, whichever occurs first.	Up to approximately 44 months
Overall Survival (OS)	OS is defined as time from first dose of study intervention to death due to any cause.	Up to approximately 44 months
Blood Concentrations of Steroids	Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids.	At designated timepoints (up to approximately 44 months)

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Orion Corporation, Orion Pharma
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2024
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): October 14, 2027

Study Registration Dates

• First Submitted: November 13, 2023
• First Submitted That Met QC Criteria: November 13, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Fludrocortisone
• Other Study ID Numbers: 5684-001; MK-5684-001 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No