(UroToday.com) The 2025 Society of Urologic Oncology (SUO) Annual Meeting featured a prostate cancer poster session during which Dr. Arif Hussain presented a trial-in-progress update for OMAHA-01A, a global phase 1/2 substudy evaluating opevesostat (MK-5684)—a first-in-class, oral CYP11A1 inhibitor—as monotherapy or in combination with several standard therapies for men with metastatic castration-resistant prostate cancer (mCRPC).
Opevesostat suppresses steroidogenesis upstream of all androgen pathways by inhibiting CYP11A1, a mitochondrial cholesterol side-chain cleavage enzyme responsible for the first step of steroid hormone synthesis. Through this mechanism, the drug reduces production of all steroid hormones that can drive prostate cancer growth, offering a mechanistically distinct approach from androgen receptor–targeted therapies.
This substudy of the OMAHA program is designed to characterize the safety, tolerability, pharmacodynamic effects, and preliminary antitumor activity across multiple treatment contexts.
Across phase 1 and phase 2 components, the study aims to evaluate the:
- Safety and tolerability of opevesostat alone and in combinations
- PSA response rates
- Radiographic progression-free survival (rPFS)
- Overall survival (OS)
These objectives reflect a comprehensive early-phase evaluation of a therapy targeting steroidogenesis at its origin.
OMAHA-01A is an open-label, randomized, phase 1/2, multicenter study enrolling an estimated 220 participants with mCRPC across more than 15 countries. Adults (≥18 years) are eligible if they have disease progression despite androgen deprivation therapy and 1–2 prior androgen receptor pathway inhibitors (ARPIs).
Participants are randomized 1:1:1:1 to one of four treatment groups:
- Opevesostat 5 mg BID (+ dexamethoasone 1.5 mg QD + fludrocortisone 0.1 mg QD in all arms)
- Opevesostat + olaparib
- Opevesostat + docetaxel
- Opevesostat + cabazitaxel
The study endpoints are:
- Safety and adverse event patterns
- PSA response
- Radiographic progression-free survival (rPFS)
- Overall survival (OS)
OMAHA-01A includes sites across Australia, Canada, Chile, Colombia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, New Zealand, Poland, Republic of Korea, Spain, Taiwan, Turkey, the United Kingdom, and the United States, illustrating the global reach of the program.
Dr. Hussain concluded as follows:
- Opevesostat (MK-5684) is a novel CYP11A1 inhibitor that suppresses upstream steroid hormone production, representing a mechanistically distinct therapeutic approach for mCRPC.
- OMAHA-01A evaluates this agent alone and in combinations with PARP inhibition and taxane chemotherapy.
- The global phase 1/2 design allows for comprehensive characterization of safety, pharmacodynamics, and preliminary antitumor activity.
- Enrollment is ongoing, and results will clarify the role of steroidogenesis blockade as a therapeutic strategy in advanced prostate cancer.
Presented by: Arif Hussain, Professor, Medical Oncology, Hematology Oncology, University of Maryland, Baltimore, MD
Written by: Rashid K. Sayyid, MD, MSc, Assistant Professor, Urologic Oncologist, Department of Urology at The University of Arizona and Banner University Medical Center – Tucson, AZ, @rksayyid on X during the 2025 Society of Urologic Oncology (SUO) annual meeting held in Phoenix, AZ, between the 2nd and 5th of December 2025.