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)
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.
Arms & interventions
- DrugOpevesostat
Administered orally
- DrugAbiraterone acetate
Administered orally
- DrugEnzalutamide
Administered orally
- DrugHydrocortisone
Administered orally or IM as a rescue medication
- DrugFludrocortisone acetate
Administered orally
- DrugPrednisone
Administered orally
- DrugDexamethasone
Administered orally as rescue medication
Outcome measures
Primary
Overall Survival (OS) in Androgen Receptor Ligand Binding Domain (AR LBD) Mutation-Positive Participants
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.
Time frame: Up to ~54 months
OS in AR LBD Mutation-Negative Participants
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.
Time frame: Up to ~54 months
Secondary
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
Time frame: Up to ~36 months
rPFS Per Prostate Cancer Working Group-modifiedRECIST 1.1 as Assessed by Blinded Independent Central Review in AR LBD Mutation-Negative Participants
Time frame: Up to ~36 months
Time to Initiation of the First Subsequent Anti-Cancer Therapy or Death (TFST)
Time frame: Up to ~54 months
Objective Response (OR)
Time frame: Up to ~54 months
Duration of Response (DOR)
Time frame: Up to ~54 months
Time to Pain Progression (TTPP)
Time frame: Up to ~54 months
Time to Prostate-specific Antigen (PSA) Progression
Time frame: Up to ~54 months
Time to First Symptomatic Skeletal-related Event (SSRE)
Time frame: Up to ~54 months
Number of Participants Who Experience an Adverse Event
Time frame: Up to ~54 months
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event
Time frame: Up to ~54 months
Eligibility criteria
Study locations (44)
University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)
Orange, California, 92868
Stanford Cancer Center ( Site 0036)
Palo Alto, California, 94304
Kaiser Permanente Riverside Medical Center ( Site 0099)
Riverside, California, 92505
Anschutz Cancer Pavilion ( Site 0046)
Aurora, Colorado, 80045
University of Colorado Health - Highlands Ranch Hospital ( Site 0111)
Highlands Ranch, Colorado, 80129
Colorado Clinical Research ( Site 0067)
Lakewood, Colorado, 80228
University of Colorado Health - Lone Tree Medical Center ( Site 0112)
Lone Tree, Colorado, 80124
Yale-New Haven Hospital-Yale Cancer Center ( Site 0064)
New Haven, Connecticut, 06510
Florida Cancer Specialists - South ( Site 7003)
Fort Myers, Florida, 33901
Bruce W. Carter Veterans Affairs Medical Center ( Site 0082)
Miami, Florida, 33125
University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0051)
Miami, Florida, 33136
University of Illinois at Chicago ( Site 0105)
Chicago, Illinois, 60612
University of Chicago Medical Center ( Site 0045)
Chicago, Illinois, 60637
University of Iowa ( Site 0047)
Iowa City, Iowa, 52242
University of Kentucky Chandler Medical Center ( Site 0048)
Lexington, Kentucky, 40536
Ochsner Clinic Foundation ( Site 0108)
New Orleans, Louisiana, 70121
Baltimore Veterans Affairs Medical Center ( Site 0069)
Baltimore, Maryland, 21201
Greenebaum Comprehensive Cancer Center ( Site 0049)
Baltimore, Maryland, 21201
Henry Ford Hospital ( Site 0015)
Detroit, Michigan, 48202
M Health Fairview Clinics and Surgery Center ( Site 0019)
Minneapolis, Minnesota, 55455
Metro-Minnesota Community Clinical Oncology ( Site 0014)
Saint Louis Park, Minnesota, 55416
Washington University School of Medicine-Internal Medicine/Oncology ( Site 0062)
St Louis, Missouri, 63110
University Of Nebraska Medical Center-Oncology/Hematology ( Site 0095)
Omaha, Nebraska, 68105
Comprehensive Cancer Centers of Nevada ( Site 0010)
Las Vegas, Nevada, 89148
Atlantic Health System Morristown Medical Center ( Site 0115)
Morristown, New Jersey, 07960
Rutgers Cancer Institute of New Jersey ( Site 0033)
New Brunswick, New Jersey, 08901
James J. Peters VA Medical Center ( Site 0088)
The Bronx, New York, 10468
University Hospitals Cleveland Medical Center ( Site 0043)
Cleveland, Ohio, 44106
Oregon Health and Science University ( Site 0028)
Portland, Oregon, 97239
VA Portland Health Care System ( Site 0058)
Portland, Oregon, 97239
AHN Allegheny General Hospital ( Site 0001)
Pittsburgh, Pennsylvania, 15212
Ralph H. Johnson VA Health Care System (RHJVAHCS)-Urology ( Site 0083)
Charleston, South Carolina, 29401
Avera Cancer Institute - Pierre ( Site 0118)
Pierre, South Dakota, 57501
Avera Cancer Institute- Research ( Site 0094)
Sioux Falls, South Dakota, 57105
Avera Cancer Institute - Yankton ( Site 0117)
Yankton, South Dakota, 57078
SCRI Oncology Partners ( Site 7000)
Nashville, Tennessee, 37203
Texas Oncology - Central/South Texas ( Site 8003)
Austin, Texas, 78731
Texas Oncology - DFW ( Site 8001)
Dallas, Texas, 75246
Texas Oncology - Gulf Coast ( Site 8002)
The Woodlands, Texas, 77380
University of Virginia Health System ( Site 0054)
Charlottesville, Virginia, 22908
VCU Health Adult Outpatient Pavillion ( Site 0061)
Richmond, Virginia, 23219
Blue Ridge Cancer Care ( Site 0004)
Roanoke, Virginia, 24014
Fred Hutchinson Cancer Center ( Site 0013)
Seattle, Washington, 98109
MEDICAL COLLEGE OF WISCONSIN ( Site 0020)
Milwaukee, Wisconsin, 53226
References
- Yu EY, Gratzke C, Burotto M, Zhang AY, Levesque E, Ortega F, Peer A, Vile D, Chen ZH, Song Y, Schloss C, Todoric J, Garratt C, Poehlein C, Antonarakis ES, Fizazi K. Steroidogenesis inhibitor opevesostat (MK-5684) for metastatic castration-resistant prostate cancer: OMAHA-003 and OMAHA-004 trial designs. Future Oncol. 2026 Mar;22(7):765-772. doi: 10.1080/14796694.2025.2595914. Epub 2026 Feb 23.(PubMed)