Prostatic Neoplasms, Metastatic Castration-Resistant Prostate Cancer
Conditions
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.
Detailed description
After approval of Protocol amendment 03, participants in the survival follow-up phase will have a final survival contact and then be discontinued from the study.
Interventions
DRUGOpevesostat
Tablets to be taken orally.
DRUGDexamethasone
Tablets to be taken orally.
Tablet to be taken orally.
DRUGHydrocortisone
Tablets to be taken orally as a recue medication.
Sponsors
Merck Sharp & Dohme LLC
Orion Corporation, Orion Pharma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 28 days | 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. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 24 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 24 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Cmax. |
| Time to Maximum Plasma Concentration (Tmax) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Tmax. |
| Area Under the Curve from Time 0 to 12 hours postdose (AUC0-12) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the AUC0-12. |
| Apparent Volume of Distribution (Vz/F) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the Vz/F. |
| Oral Clearance (CL/F) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the CL/F. |
| Half-Life (t½) of opevesostat | Day 1, Day 8, Day 29, and at first visit after the last dose of opevesostat (up to approximately 24 months) | Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine the t½. |
| Prostate-specific Antigen (PSA) response | Up to approximately 24 months | Percentage of participants in the analysis population who have a reduction in PSA level of ≥50% measured twice ≥3 weeks apart. |
| Time to Prostate-specific Antigen (PSA) Progression | Up to approximately 24 months | 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. |
| 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 | Up to approximately 24 months | Time from first dose of study drug to radiographic progression, or death due to any cause, whichever occurs first. |
| 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 | Up to approximately 24 months | 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. |
| 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 | Up to approximately 24 months | 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. |
| Overall Survival (OS) | Up to approximately 24 months | Time from first dose of study intervention to death due to any cause. |
| 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) | Blood samples collected at multiple timepoints after the administration of opevesostat will be used to determine the blood concentrations of steroids. |
Countries
Japan
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed