Clinical trial NCT06136598: A Study of Opevesostat (MK-5684) in China Participants With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (MK-5684-001)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Prostatic Neoplasms
Metastatic Castration-Resistant Prostate Cancer
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2023-11-18
Enrollment: 14
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 20 months
measure: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 20 months
measure: Maximum Plasma Concentration (Cmax) of opevesostat
timeFrame: 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
measure: Time to Maximum Plasma Concentration (Tmax) of opevesostat
timeFrame: 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
measure: Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of opevesostat
timeFrame: 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
measure: Oral Clearance (CL/F) of opevesostat
timeFrame: 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
measure: Half-Life (t1/2) of opevesostat
timeFrame: 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:
measure: Prostate-specific Antigen (PSA) Response Rate
timeFrame: Up to approximately 37 months
measure: Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 37 months
measure: Objective Response Rate (ORR) Per PCWG-modified RECIST 1.1
timeFrame: Up to approximately 37 months
measure: Duration of Response (DOR) Per PCWG-modified RECIST 1.1
timeFrame: Up to approximately 37 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 37 months
measure: Blood Concentrations of Steroids
timeFrame: At designated timepoints (up to approximately 37 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University First Hospital-Urology ( Site 0001)
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center-Neurosurgery department ( Site 0003)
state: Guangdong
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical,Science & Technology ( Site 0002)
state: Hubei
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: