Clinical trial NCT06104449: A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)
Official title: A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC)
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: 2023-10-27
Enrollment: 6
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 purpose of this study is to assess the efficacy and safety of opevesostat in the treatment of Japanese men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with Next Generation Hormonal Agent (NHA) and taxane-based chemotherapy.


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 current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease by computed tomography/magnetic resonance imaging (CT/MRI)
* Has ongoing androgen deprivation with serum testosterone \<50 ng/dL (\<1.7 nmol/L)
* Participants receiving bone anti-resorptive therapy (including, but not limited to bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks prior to the start of study intervention.
* Has progressed on or after treatment with at least 1 line of NHAs in metastatic hormone-sensitive prostate cancer (mHSPC) or in castration-resistant prostate cancer (CRPC) for a minimum of 12 weeks (e.g. abiraterone, enzalutamide, darolutamide, apalutamide), and with at least 1 line of taxane-based chemotherapy in mHSPC or in CRPC, or ineligibility for chemotherapy
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to allocation
* If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat: Refrain from donating sperm, plus EITHER be abstinent OR must agree to use male condom.

Exclusion Criteria:

* Has a history of pituitary dysfunction
* Has brain metastases
* History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
* Has an active or uncontrolled autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
* Has an active infection or other medical condition that would make corticosteroid contraindicated
* Has serious persistent infection within 2 weeks prior to the start of the study intervention
* Participants on an unstable dose of thyroid hormone therapy within 6 months prior to the start of the study intervention
* Has poorly controlled diabetes mellitus
* Hypotension: systolic blood pressure (BP) \< 110 mmHg, or uncontrolled hypertension: systolic BP ≥ 160 mmHg or diastolic BP ≥ 95 mmHg, in 2 out of 3 recordings with optimized antihypertensive therapy
* Has active or unstable cardio/cerebro-vascular disease, including thromboembolic event
* Is unable to swallow orally administered medication or known gastrointestinal (GI) disease or GI procedure that may interfere with absorption of study intervention
* Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to the start of the study intervention and not adequately recovered from the toxicities and/or complications
* Has received aldosterone antagonist (e.g. spironolactone, eplerenone) and phenytoin within 4 weeks prior to the start of the study intervention
* Has received radiotherapy within 4 weeks prior to the start of the study intervention, or radiation related toxicities, requiring corticosteroids
* Has received chemotherapy within the last 4 weeks (2 weeks for oral or weekly chemotherapy; 6 weeks for nitrosoureas and mitomycin C) prior to the start of the study intervention
* Has received prior enzalutamide and apalutamide within 3 weeks, or abiraterone and darolutamide within 2 weeks prior to the start of the study intervention
* Systemic use of the following medications within 2 weeks prior to the start of study intervention: strong cytochrome P450 (CYP)3A4 inducers: e.g., carbamazepine, rifampicin, phenobarbital, phenytoin, St John's Wort) and strong CYP3A4 inhibitors: e.g., itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, telithromycin, grapefruit juice
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
* Has used herbal products that may have hormonal anti-prostate cancer activity and/or are known to decrease PSA levels (eg, saw palmetto) within 4 weeks prior to the start of the study intervention
* Has received treatment with 5-α reductase inhibitors (eg, finasteride or dutasteride), estrogens, and/or cyproterone within 4 weeks prior to the start of the study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* History of human immunodeficiency virus (HIV) infection
* Has a history of Hepatitis B or active Hepatitis C virus
* Has a "superscan" bone scan
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the start of the study intervention

Primary outcomes:
measure: Number of Participants Who Experience a Dose-limiting Toxicity (DLT) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 by the Investigator
timeFrame: Up to 28 days
measure: Number of Participants Who Experience an Adverse Event (AE)
timeFrame: Up to approximately 24 months
measure: Number of Participants Who Discontinue Study Intervention Due to an AE
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Maximum Plasma Concentration (Cmax) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Time to Maximum Plasma Concentration (Tmax) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Apparent Volume of Distribution (Vz/F) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Oral Clearance (CL/F) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Half-Life (t½) of opevesostat
timeFrame: Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
measure: Prostate-specific Antigen (PSA) response
timeFrame: Up to approximately 24 months
measure: Time to Prostate-specific Antigen (PSA) Progression
timeFrame: Up to approximately 24 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) as Assessed by Investigator
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator
timeFrame: Up to approximately 24 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 24 months
measure: Blood Concentrations of Steroids
timeFrame: Day 1, Day 8, Day 29, Day 85, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East ( Site 0001)
state: Chiba
city: Sakura
country: Japan
facility: Toho University Sakura Medical Center ( Site 0003)
state: Chiba
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center ( Site 0002)
state: Kanagawa
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: