A Study of Opevesostat (MK-5684) in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001)
- Conditions
- Prostatic NeoplasmsMetastatic Castration-Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT06136598
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 14
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Opevesostat 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. Opevesostat Hydrocortisone 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. Opevesostat Fludrocortisone 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. Opevesostat Dexamethasone 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.
- Primary Outcome Measures
Name Time Method Area Under the Curve from Time 0 to 12 hours postdose (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 Blood samples will be collected at pre-specified timepoints to determine the AUC0-12 of opevesostat.
Number of Participants Who Experience an Adverse Event (AE) Up to approximately 20 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 20 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 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 Blood samples will be collected at pre-specified timepoints to determine the Cmax of opevesostat.
Time to Maximum Plasma Concentration (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 Blood samples will be collected at pre-specified timepoints to determine the Tmax of opevesostat.
Apparent Volume of Distribution (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 Blood samples will be collected at pre-specified timepoints to determine the Vz/F of opevesostat.
Oral Clearance (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 Blood samples will be collected at pre-specified timepoints to determine the CL/F of opevesostat.
Half-Life (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 Blood samples will be collected at pre-specified timepoints to determine the t1/2 of opevesostat.
- Secondary Outcome Measures
Name Time Method Prostate-specific Antigen (PSA) Response Rate Up to approximately 37 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 37 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 37 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 37 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 37 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 37 months) Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids.
Trial Locations
- Locations (3)
Peking University First Hospital-Urology ( Site 0001)
🇨🇳Beijing, Beijing, China
Tongji Hospital Tongji Medical,Science & Technology ( Site 0002)
🇨🇳Wuhan, Hubei, China
Sun Yat-sen University Cancer Center-Neurosurgery department ( Site 0003)
🇨🇳Guangzhou, Guangdong, China