Steroidogenesis inhibitor opevesostat (MK-5684) for metastatic castration-resistant prostate cancer: OMAHA-003 and OMAHA-004 trial designs
Treatment options for metastatic castration-resistant prostate cancer (mCRPC) include androgen receptor pathway inhibitors (ARPIs), taxanes, radium-223, Lu-PSMA, poly (ADP-ribose) polymerase inhibitors, and immunotherapy in select patients. Resistance to ARPIs and hormone-based therapies has been associated with AR-ligand-binding domain mutations that can lead to promiscuous stimulation by other steroid hormones. There is a need to explore alternative targets and develop next-generation ARPIs or combination therapies that overcome this resistance. We describe the rationale and design of the randomized phase III trials OMAHA-003 (NCT06136624) and OMAHA-004 (NCT06136650), which will evaluate the efficacy and safety of opevesostat, a steroidogenesis inhibitor, versus ARPI switch in previously treated mCRPC. Results may support opevesostat as a potential new treatment option for mCRPC.<b>Clinical trial registration:</b> www.clinicaltrials.gov identifiers are NCT06136624 and NCT06136650.
Authors
- Yue Song (ORCID: https://orcid.org/0000-0003-0898-5281)
- Karim Fizazi (ORCID: https://orcid.org/0000-0002-6068-9474)
- Éric Lévesque (ORCID: https://orcid.org/0000-0001-5986-3458)
- Christian Poehlein (ORCID: https://orcid.org/0000-0002-3348-3059)
- C. Gratzke
- Charles Schloss (ORCID: https://orcid.org/0000-0002-5106-3082)
- Chris Garratt (ORCID: https://orcid.org/0000-0002-2137-1017)
- Mauricio Burotto (ORCID: https://orcid.org/0000-0002-7150-4033)
- Donald Charles Vile
- Jelena Todoric (ORCID: https://orcid.org/0000-0002-2669-3904)
- A. Peer
- Zheng Hong Chen
- Evan Yi-Wen Yu (ORCID: https://orcid.org/0000-0001-7825-5087)
- Francisco Ortega
- Emmanuel S Antonarakis
- Alison Y Zhang
Institutions
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- University of Washington (US)
- Université Paris-Saclay (FR)
- Catholic University of the Maule (CL)
- University of Minnesota System (US)
- University Medical Center Freiburg (DE)
- Rambam Health Care Campus (IL)
- Mountain Blue Cancer Care Center (US)
- Finis Terrae University (CL)
- Université Laval (CA)
- Orion Corporation (United Kingdom) (GB)
- Macquarie University (AU)
Publication Details
- Journal
- Future Oncology
- Published
- 2026-02-23
- DOI
- https://doi.org/10.1080/14796694.2025.2595914
- Primary Topic
- Prostate Cancer Treatment and Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00