A Study of Opevesostat (MK-568)4 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (MK-5684-005)

Prostatic Neoplasms Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT06104449
• Other study ID #: 5684-005
• Secondary ID: MK-5684-005jRCT2
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 14, 2023
• Est. completion date: January 12, 2026

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 6
• Est. completion date: January 12, 2026
• Est. primary completion date: January 12, 2026
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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-a 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

Related Conditions & MeSH terms

• Metastatic Castration-Resistant Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Opevesostat
Tablets to be taken orally.
• Dexamethasone
Tablets to be taken orally.
• Fludrocortisone acetate
Tablet to be taken orally.
• Hydrocortisone
Tablets to be taken orally as a recue medication.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East ( Site 0001)	Kashiwa	Chiba
Japan	Toho University Sakura Medical Center ( Site 0003)	Sakura	Chiba
Japan	Yokohama City University Medical Center ( Site 0002)	Yokohama	Kanagawa

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Orion Corporation, Orion Pharma

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The following events, if considered drug related by the Investigator, will be considered a DLT: Grade 4 hematologic toxicity lasting =7 days, except anemia and thrombocytopenia; Grade 3 nausea, vomiting, diarrhea or fatigue lasting >3 days despite optimal supportive care; other nonhematologic grade =3 toxicities of any duration (not laboratory); Grade =3 nonhematologic laboratory abnormality (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; missing >25% of opevesostat doses as a result of drug-related AE(s) during the first 28 days; Grade 5 toxicity. The number of participants who experience a DLT will be presented.	Up to 28 days
Primary	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 24 months
Primary	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 24 months
Secondary	Maximum Plasma Concentration (Cmax) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Time to Maximum Plasma Concentration (Tmax) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-12.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Apparent Volume of Distribution (Vz/F) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Vz/F.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Oral Clearance (CL/F) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the CL/F.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Half-Life (t½) of opevesostat	Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t½.	Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months)
Secondary	Prostate-specific Antigen (PSA) response	Percentage of participants in the analysis population who have a reduction in PSA level of =50% measured twice =3 weeks apart.	Up to approximately 24 months
Secondary	Time to Prostate-specific Antigen (PSA) Progression	Time from first dose of study drug to PSA progression. PSA progression date is defined as the date of 1) =25% increase and =2 ng/mL above the nadir, confirmed by a second value =3 weeks later if there is PSA decline from baseline, or 2) =25% increase and =2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.	Up to approximately 24 months
Secondary	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	Time from first dose of study drug to radiographic progression, or death due to any cause, whichever occurs first.	Up to approximately 24 months
Secondary	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	Percentage of participants in the analysis population who have a best overall response of either confirmed Complete Response (CR) or a confirmed Partial Response (PR) per PCWG-modified RECIST 1.1.	Up to approximately 24 months
Secondary	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	Time from first documented evidence of confirmed Complete Response (CR) or Partial Response (PR) per PCWG-modified RECIST 1.1 until disease progression or death from any cause, whichever occurs first.	Up to approximately 24 months
Secondary	Overall Survival (OS)	Time from first dose of study intervention to death due to any cause.	Up to approximately 24 months
Secondary	Blood Concentrations of Steroids	Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids.	Day 1, Day 8, Day 29, Day 85, and at first visit after the last dose of opevesostat (up to approximately 24 months)

External Links

•   Merck Clinical Trials Information