Steroidogenesis inhibitor ODM-209 for metastatic castration-resistant prostate cancer and advanced breast cancer: Results from the first-in-human STESIDES study.
Alice Bernard-Tessier, Iben Spanggaard, Tapio Utriainen et al.
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In 30 seconds
The multicentre, first-in-human phase 1 STESIDES dose-finding study evaluated oral ODM-209, a CYP11A1 inhibitor, in adults with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC) and advanced breast cancer (aBC). Thirty-eight participants received treatment: 34 with mCRPC and four with aBC. All experienced adverse events, and steroid hormone concentrations were mostly undetectable. A prostate-specific antigen decline of at least 50% occurred in 10 (29%) participants with mCRPC, including 9/19 (47%) with activating androgen receptor ligand-binding domain mutations. No responses were observed in aBC.
Key findings
- All 38 participants experienced adverse events; fatigue (53%) and peripheral edema (34%) were most common.
- Nine (24%) participants had grade ≥ 3 adverse events related to ODM-209; three (8%) had serious adrenal insufficiency events.
- PSA decline ≥ 50% occurred in 10 (29%) participants with mCRPC, including 9/19 (47%) with activating AR-LBD mutations.
- Three of 16 (19%) evaluable participants with mCRPC had a partial clinical response; no responses were seen in aBC.
Why it matters
The findings provide early clinical evidence that inhibiting steroid hormone synthesis may have antitumour activity in some patients with heavily pretreated mCRPC, with a notable PSA response rate among those with activating AR-LBD mutations. The adrenal insufficiency events also underscore the importance of monitoring and replacement therapy in studies of this approach.
What to keep in mind
This was a phase 1 dose-finding study with 38 participants, including only four with aBC; the reported activity is early-phase evidence.