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

Study Overview
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Brief Summary
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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.

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

Conditions
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Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer

Intervention / Treatment
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* Drug: MK-5684
* Drug: Dexamethasone
* Drug: Fludrocortisone
* Drug: Hydrocortisone


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MK-5684<br>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<br>* Tablets to be taken orally.<br>Drug: Dexamethasone<br>* Tablets to be taken orally<br>* Other names: Dexamethasone acetate;Drug: Fludrocortisone<br>* Tablets to be taken orally.<br>* Other names: Fludrocortisone acetate;Drug: Hydrocortisone<br>* Tablet to be taken orally as a rescue medication.<br>* Other names: Hydrocortisone acetate;|

What is the study measuring?
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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 21 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 21 months | 
| Maximum Plasma Concentration (Cmax) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 
| Time to Maximum Plasma Concentration (Tmax) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 
| Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 
| Apparent Volume of Distribution (Vz/F) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 
| Oral Clearance (CL/F) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 
| Half-Life (t1/2) of MK-5684 | Blood samples will be collected at pre-specified timepoints to determine the 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 | 

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 26 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 26 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 26 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 26 months | 
| Overall Survival (OS) | OS is defined as time from first dose of study intervention to death due to any cause. | Up to approximately 26 months | 
| Blood Concentrations of Steroids | Blood samples collected at multiple timepoints after the administration of MK-5684 will be used to determine the blood concentrations of steroids. | At designated timepoints (up to approximately 26 months) |