Investigational Drug
Opevesostat
TrialFetch AI Analysis
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Overview
Opevesostat (MK-5684, formerly ODM-208) is an investigational oral drug being studied for metastatic castration-resistant prostate cancer (mCRPC). Early human results are available from the phase 1/2 CYPIDES study; phase 3 trials are evaluating whether it improves outcomes compared with a switch to another androgen-receptor–pathway treatment. (evidence.nejm.org)
Mechanism of action
Opevesostat inhibits CYP11A1, the enzyme that catalyzes the first step in steroid-hormone synthesis. This suppresses production of androgens and other steroids. Because it also suppresses adrenal hormones, trial participants receive glucocorticoid and mineralocorticoid replacement. (evidence.nejm.org)
Efficacy
In an updated, open-label CYPIDES phase 2 analysis of 134 previously treated patients, a PSA50 response—a prostate-specific antigen decline of at least 50%—occurred in 53.0% of patients with an androgen-receptor ligand-binding-domain mutation and 14.7% of those without one. The reported objective tumor response rate was 18.6% in the mutation-positive group. These are preliminary, uncontrolled results; a PSA decline alone does not establish longer survival or clinical benefit. (annalsofoncology.org)
Safety
In the peer-reviewed CYPIDES report, treatment-related adrenal insufficiency occurred in 6 of 45 patients (13.3%) receiving the phase 2 dose of 5 mg twice daily, despite hormone replacement; three had serious events. Anemia and fatigue were each reported in 37.8% of phase 2 patients. Treatment-emergent adverse events led to permanent discontinuation in 22.2%; investigators attributed no deaths to opevesostat. (evidence.nejm.org)
Further reading
- CYPIDES phase 1/2 results, NEJM Evidence
- Updated phase 2 results, Annals of Oncology conference abstract
- OMAHA-003 and OMAHA-004 phase 3 trial designs
Last updated: Sep 2026
Active trials using Opevesostat
Found 4 active trials using this drug:
TrialFetch AI summary: This study enrolls patients with metastatic castration-resistant prostate adenocarcinoma progressing despite androgen deprivation after one or two androgen receptor pathway inhibitors, with no prior taxane chemotherapy for mCRPC. Treatments are docetaxel, ifinatamab deruxtecan (a B7-H3–targeted antibody–drug conjugate delivering a topoisomerase I inhibitor), or ifinatamab deruxtecan combined with opevesostat (a CYP11A1 inhibitor), abiraterone, or enzalutamide.
ClinicalTrials.gov ID: NCT06863272
TrialFetch AI summary: Adults with metastatic castration-resistant prostate adenocarcinoma progressing despite androgen deprivation and one or two novel hormonal agents receive opevesostat alone or with olaparib, docetaxel, or cabazitaxel. Opevesostat is an investigational CYP11A1 inhibitor that suppresses steroid synthesis, including androgen production, and requires adrenal hormone replacement.
ClinicalTrials.gov ID: NCT06353386
TrialFetch AI summary: Patients with mCRPC progressing after a next-generation hormonal agent and one or two taxane regimens are randomized to opevesostat or an alternative androgen receptor–pathway therapy (abiraterone acetate or enzalutamide). Opevesostat inhibits CYP11A1 to suppress steroid and androgen synthesis and is given with corticosteroid replacement; overall survival is assessed separately by AR ligand-binding-domain mutation status.
ClinicalTrials.gov ID: NCT06136624
TrialFetch AI summary: Adults with mCRPC progressing after one next-generation hormonal agent, ECOG 0–1, and no prior taxane for mCRPC are randomized to opevesostat with adrenal hormone replacement or a switch to abiraterone plus prednisone or enzalutamide. Opevesostat inhibits CYP11A1 to suppress steroid and androgen synthesis.
ClinicalTrials.gov ID: NCT06136650
