Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)

NCT06136624
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Phase
Phase 3
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Recruitment status
Recruiting
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Participants
1,310
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Lead sponsor
Merck Sharp & Dohme LLC
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Start date
2023-12-31
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Number of sites
288
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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) 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 in androgen receptor ligand binding domain (AR LBD) mutation-negative and -positive participants.
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Acronym
OMAHA-003
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Short title
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)
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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 (OMAHA-003)
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Control arm
Active comparator
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2030-02-15
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First posted
2023-11-18
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Registry last updated
2026-08-28
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Primary completion date
2028-08-02
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Start date
2023-12-31
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Participants
1,310
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Participant count basis
Estimated
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Planned participants
1,310
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Protocol amendments
6
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Number of sites
288
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Merck Sharp & Dohme LLC
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06136624
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ClinicalTrials.gov ID
NCT06136624
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Overall Survival (OS) in Androgen Receptor Ligand Binding Domain (AR LBD) Mutation-Positive Participants

    Timeframe: 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

    Timeframe: 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.

  1. 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 Participants

    Timeframe: 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.

  2. rPFS Per Prostate Cancer Working Group-modifiedRECIST 1.1 as Assessed by Blinded Independent Central Review in AR LBD Mutation-Negative Participants

    Timeframe: 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.

  3. Time to Initiation of the First Subsequent Anti-Cancer Therapy or Death (TFST)

    Timeframe: 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.

  4. Objective Response (OR)

    Timeframe: Up to ~54 months

    OR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

  5. Duration of Response (DOR)

    Timeframe: Up to ~54 months

    DOR is determined by PCWG-modified RECIST 1.1 as assessed by BICR.

  6. Time to Pain Progression (TTPP)

    Timeframe: 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).

  7. Time to Prostate-specific Antigen (PSA) Progression

    Timeframe: 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.

  8. Time to First Symptomatic Skeletal-related Event (SSRE)

    Timeframe: 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 non-vertebral); 3) spinal cord compression; or 4) tumor-related orthopedic surgical intervention.

  9. Number of Participants Who Experience an Adverse Event

    Timeframe: 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.

  10. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event

    Timeframe: 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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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 distant metastatic disease (M1 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

  • 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, citrus pectin polysaccharide) 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
Sources for eligibility
clinicaltrials.gov

  • University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)Orange, United StatesCompleted
  • Stanford Cancer Center ( Site 0036)Palo Alto, United StatesRecruiting
  • Kaiser Permanente Riverside Medical Center ( Site 0099)Riverside, United StatesRecruiting
  • Anschutz Cancer Pavilion ( Site 0046)Aurora, United StatesRecruiting
  • University of Colorado Health - Highlands Ranch Hospital ( Site 0111)Highlands Ranch, United StatesRecruiting
  • Colorado Clinical Research ( Site 0067)Lakewood, United StatesCompleted
  • University of Colorado Health - Lone Tree Medical Center ( Site 0112)Lone Tree, United StatesRecruiting
  • Yale-New Haven Hospital-Yale Cancer Center ( Site 0064)New Haven, United StatesRecruiting
  • Florida Cancer Specialists - South ( Site 7003)Fort Myers, United StatesCompleted
  • Bruce W. Carter Veterans Affairs Medical Center ( Site 0082)Miami, United StatesCompleted
  • University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0051)Miami, United StatesRecruiting
  • University of Illinois at Chicago ( Site 0105)Chicago, United StatesRecruiting
  • University of Chicago Medical Center ( Site 0045)Chicago, United StatesRecruiting
  • University of Iowa ( Site 0047)Iowa City, United StatesCompleted
  • University of Kentucky Chandler Medical Center ( Site 0048)Lexington, United StatesCompleted
  • Ochsner Clinic Foundation ( Site 0108)New Orleans, United StatesCompleted
  • Baltimore Veterans Affairs Medical Center ( Site 0069)Baltimore, United StatesRecruiting
  • Greenebaum Comprehensive Cancer Center ( Site 0049)Baltimore, United StatesRecruiting
  • Henry Ford Hospital ( Site 0015)Detroit, United StatesCompleted
  • Avera Cancer Institute - Marshall ( Site 0122)Marshall, United StatesRecruiting
  • M Health Fairview Clinics and Surgery Center ( Site 0019)Minneapolis, United StatesRecruiting
  • Metro-Minnesota Community Clinical Oncology ( Site 0014)Saint Louis Park, United StatesActive, not recruiting
  • Hattiesburg Clinic Hematology/Oncology ( Site 0120)Hattiesburg, United StatesRecruiting
  • Washington University School of Medicine-Internal Medicine/Oncology ( Site 0062)St Louis, United StatesRecruiting
  • University Of Nebraska Medical Center-Oncology/Hematology ( Site 0095)Omaha, United StatesRecruiting

And 263 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • MK-5684-003
  • 2023
  • U1111-1287-5304
  • 2023-504899-25-00
  • jRCT2031240029
Sources for references
clinicaltrials.gov

Related records

Drugs (7)

Lead sponsors (1)

Conditions (1)

Targets (4)