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

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06136598

Collaborator

(none)

Enrollment

Arm

26.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the safety and tolerability of MK-5684 in the treatment of male Chinese participants with metastatic castration-resistant prostate cancer (mCRPC) and to characterize the pharmacokinetic profile of MK-5684. There are no formal hypotheses to be tested in this study.

Condition or Disease	Intervention/Treatment	Phase
Prostatic Neoplasms Metastatic Castration-Resistant Prostate Cancer	Drug: MK-5684 Drug: Dexamethasone Drug: Fludrocortisone Drug: Hydrocortisone	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

14 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Dec 25, 2023

Anticipated Primary Completion Date :

Oct 20, 2025

Anticipated Study Completion Date :

Feb 28, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MK-5684 Participants will receive MK-5684 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: MK-5684 Tablets to be taken orally. 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

Arm

Intervention/Treatment

Experimental: MK-5684

Participants will receive MK-5684 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: MK-5684

Tablets to be taken orally.

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

Outcome Measures

Primary Outcome Measures

Number of Participants Who Experience an Adverse Event (AE) [Up to approximately 21 months]
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.
Number of Participants Who Discontinue Study Intervention Due to an AE [Up to approximately 21 months]
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.
Maximum Plasma Concentration (Cmax) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the Cmax of MK-5684.
Time to Maximum Plasma Concentration (Tmax) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the Tmax of MK-5684.
Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the AUC0-12 of MK-5684.
Apparent Volume of Distribution (Vz/F) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the Vz/F of MK-5684.
Oral Clearance (CL/F) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the CL/F of MK-5684.
Half-Life (t1/2) of MK-5684 [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]
Blood samples will be collected at pre-specified timepoints to determine the t1/2 of MK-5684.

Secondary Outcome Measures

Prostate-specific Antigen (PSA) Response Rate [Up to Approximately 26 months]
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.
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 26 months]
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.
Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1 [Up to approximately 26 months]
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.
Duration of Response (DOR) Per PCWG-modified RECIST 1.1 [Up to approximately 26 months]
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.
Overall Survival (OS) [Up to approximately 26 months]
OS is defined as time from first dose of study intervention to death due to any cause.
Blood Concentrations of Steroids [At designated timepoints (up to approximately 26 months)]
Blood samples collected at multiple timepoints after the administration of MK-5684 will be used to determine the blood concentrations of steroids.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.