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Trial record 1 of 1 for:    MK-5684-003
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Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

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ClinicalTrials.gov Identifier: NCT06136624
Recruitment Status : Recruiting
First Posted : November 18, 2023
Last Update Posted : June 11, 2024
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Brief Summary:
This is a phase 3, randomized, open-label study of opevesostat compared to alternative abiraterone acetate or enzalutamide in participants with metastatic castration-resistant prostate cancer (mCRPC) with respect to overall survival (OS) and to radiographic progression-free survival (rPFS) per Prostate Cancer Working Group (PCWG) Modified Response Evaluation Criteria In Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) in participants with mCRPC previously treated with next-generation hormonal agent (NHA) and taxane-based chemotherapy. It is hypothesized that opevesostat is superior with respect to OS and rPFS per PCWG Modified RECIST 1.1 as assessed by BICR in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Drug: Opevesostat Drug: Abiraterone acetate Drug: Enzalutamide Drug: Hydrocortisone Drug: Fludrocortisone acetate Drug: Prednisone Drug: Dexamethasone Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Previously Treated With Next-generation Hormonal Agent (NHA) and Taxane-based Chemotherapy
Actual Study Start Date : December 31, 2023
Estimated Primary Completion Date : August 2, 2028
Estimated Study Completion Date : August 2, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arm Intervention/treatment
Experimental: Opevesostat
Participants receive opevesostat 5 mg by oral tablets twice daily (bid) plus dexamethasone 1.5 mg by oral tablets once daily (qd) and 0.1 mg fludrocortisone acetate by oral tablet qd until progression. Hydrocortisone 100 mg (oral or intramuscular [IM]) dose will also be provided to participants for use as rescue medication.
Drug: Opevesostat
Administered orally
Other Name: MK-5684

Drug: Hydrocortisone
Administered orally or IM as a rescue medication

Drug: Fludrocortisone acetate
Administered orally

Drug: Dexamethasone
Administered orally as rescue medication

Active Comparator: Abiraterone Acetate or Enzalutamide
Participants receive abiraterone 1000 mg qd by oral tablets plus prednisone 5 mg bid by oral tablets or enzalutamide 160 mg qd by oral tablets.
Drug: Abiraterone acetate
Administered orally
Other Names:
  • ZYTIGA
  • YONSA

Drug: Enzalutamide
Administered orally
Other Name: XTANDI

Drug: Prednisone
Administered orally




Primary Outcome Measures :
  1. Overall Survival (OS) in Androgen Receptor Ligand Binding Domain (AR LBD) Mutation-Positive Participants [ Time Frame: Up to ~54 months ]
    OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-positive participants will be reported for each study arm.

  2. OS in AR LBD Mutation-Negative Participants [ Time Frame: Up to ~54 months ]
    OS is defined as time from randomization to death due to any cause. OS in AR LBD mutation-negative participants will be reported for each study arm.

  3. Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review in AR LBD Mutation-Positive Participant [ Time Frame: Up to ~36 months ]
    rPFS is defined as the time from randomization to the first documented disease progression per Prostate Cancer Working Group (PCWG)-modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-positive participants will be reported for each study arm.

  4. rPFS Per Prostate Cancer Working Group-modified RECIST 1.1 as Assessed by Blinded Independent Central Review in AR LBD Mutation-Negative Participants [ Time Frame: Up to ~36 months ]
    rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death due to any cause, whichever occurs first. rPFS in AR LBD mutation-negative participants will be reported for each study arm.


Secondary Outcome Measures :
  1. Time to Initiation of the First Subsequent Anti-Cancer Therapy or Death (TFST) [ Time Frame: Up to ~54 months ]
    TFST is defined as the time from randomization to initiation of the first subsequent anticancer therapy or death, whichever occurs first.

  2. Objective Response (OR) [ Time Frame: Up to ~54 months ]
    OR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

  3. Duration of Response (DOR) [ Time Frame: Up to ~54 months ]
    DOR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

  4. Time to Pain Progression (TTPP) [ Time Frame: Up to ~54 months ]
    TTPP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm [AQA] Score).

  5. Time to Prostate-specific Antigen (PSA) Progression [ Time Frame: Up to ~54 months ]
    The time from randomization to PSA progression. The PSA progression date is defined as the date of either: 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 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline.

  6. Time to First Symptomatic Skeletal-related Event (SSRE) [ Time Frame: Up to ~54 months ]
    The time from randomization to the first occurrence of any of the following symptomatic skeletal-related events: 1) Use of EBRT to prevent or relieve skeletal symptoms; 2) new symptomatic pathologic bone fracture (vertebral or nonvertebral); 3) spinal cord compression; or 4) tumor-related orthopedic surgical intervention.

  7. Number of Participants Who Experience an Adverse Event [ Time Frame: Up to ~54 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  8. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event [ Time Frame: Up to ~54 months ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
  • Has prostate cancer progression while on androgen deprivation therapy (or post bilateral orchiectomy) within 6 months before Screening
  • 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 disease that progressed during or after treatment with 1 novel hormonal agent (NHA)
  • Has received 1 but no more than 2 taxane-based chemotherapy regimens for metastatic castration-resistant prostate cancer (mCRPC) and has had progressive disease (PD) during or after treatment
  • Has ongoing androgen deprivation with serum testosterone <50 ng/dL (<1.7 nM)
  • Has provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days of randomization
  • Has had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment
  • Has received prior 177Lu-PSMA-617 or were deemed ineligible to receive 177Lu-PSMA-617 treatment by the investigator or refused 177Lu-PSMA-617 treatment
  • Participants who have not received cabazitaxel can be enrolled if they are ineligible for cabazitaxel treatment as determined by the investigator or have refused treatment
  • If participant received first generation anti-androgen therapy before screening, the participant has evidence of disease progression >4 weeks since the last flutamide treatment and >6 weeks since the last bicalutamide or nilutamide treatment
  • Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥ 4 weeks before the date of randomization
  • Participants with human immunodeficiency virus (HIV) infection must have well controlled HIV on antiretroviral therapy (ART)
  • Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
  • Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at Screening.
  • Participants who can produce sperm must agree to the following during the study treatment period and for at least 7 days after the last dose of opevesostat, for at least 30 days after the last dose of abiraterone acetate, and for at least 3 months after the last dose of enzalutamide: EITHER be abstinent OR must agree to use male condom

Exclusion Criteria:

  • Has a gastrointestinal disorder that might affect absorption
  • Has a history of pituitary dysfunction
  • Has poorly controlled diabetes mellitus
  • Has clinically significant abnormal serum potassium or sodium level
  • Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events
  • Has a history of seizure within 6 months of providing documented informed consent or any condition that may predispose to seizures within 12 months before the date of randomization
  • Has a history of clinically significant ventricular arrhythmias
  • Has received an anticancer monoclonal antibody (mAb) within 4 weeks before the date of randomization, or has not recovered from adverse events (AEs) due to mAbs administered more than 4 weeks before the date of randomization
  • Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications
  • Participants who have not adequately recovered from major surgery or have ongoing surgical complications
  • Has used herbal or medicinal products that may have hormonal anti-prostate cancer activity and/or are known to decrease prostate-specific Antigen (PSA) (eg, saw palmetto, megesterol acetate) within 4 weeks before the date of randomization
  • Has received radium-223 or lutetium-177 within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline from AEs due to radium-223 or lutetium-177 administered more than 4 weeks before the date of randomization
  • Has received treatment with 5-αreductase inhibitors (eg, finasteride or dutasteride), estrogens, or cyproterone within 4 weeks before the date of randomization
  • Has received colony-stimulating factors within 28 days before the date of randomization
  • Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days of the date of randomization
  • Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows: enzalutamide or apalutamide within 3 weeks or abiraterone acetate + prednisone or darolutamide within 2 weeks
  • Has a "superscan" bone scan
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has an active infection requiring systemic therapy
  • Has concurrent active HBV or known active HCV infection
  • Has a history of long QTc syndrome
  • Has any of the following at Screening Visit: hypotension (systolic BP <110 mm Hg) or uncontrolled hypertension (systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 out of 3 recordings with optimized antihypertensive therapy)
  • Is unable to swallow capsules/tablets
  • Is currently being treated with cytochrome 450-inducing antiepileptic drugs for seizures
  • Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention
  • Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention
  • Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids
  • Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Systemic use of the following medications within 2 weeks before the first dose of study intervention: strong CYP3A4 inducers (eg, avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, or St John's Wort); P-gp inhibitors (eg, erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, or milk thistle [Silybum marianum])
  • Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06136624


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Show Show 113 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Orion Corporation, Orion Pharma
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
Additional Information:
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT06136624    
Other Study ID Numbers: 5684-003
2023-504899-25 ( Other Identifier: EU CT )
MK-5684-003 ( Other Identifier: Merck )
jRCT2031240029 ( Registry Identifier: Japan Registry of Clinical Trials (jRCT) )
First Posted: November 18, 2023    Key Record Dates
Last Update Posted: June 11, 2024
Last Verified: June 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
Dexamethasone
Prednisone
Hydrocortisone
Fludrocortisone
Abiraterone Acetate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists