Phase 1 study launches for novel CYP11A1 inhibitor for mCRPC

The first patient has been dosed in a phase 1 trial (NCT06801236) investigating the novel CYP11A1 inhibitor ACE-232 in patients with metastatic castration-resistant prostate cancer (mCRPC), Acerand Therapeutics announced in a news release.¹

According to the company, ACE-232 is a “highly potent and selective small-molecule inhibitor of CYP11A1, a key adrenal enzyme involved in the first and rate-limiting step of steroid hormone biosynthesis.”

In preclinical studies, ACE-232 demonstrated superior potency, efficacy, and pharmacokinetic properties compared with other CYP11A1 inhibitors. The data, which were presented at the 2025 American Association for Cancer Research Annual Meeting in Chicago, Illinois, also showed that ACE-232 was well-tolerated and demonstrated efficacy against preclinical models resistant to current therapies, including abiraterone acetate (Zytiga) and enzalutamide (Xtandi), Acerand reported.²

The FDA granted an investigational new drug clearance to the agent in January 2025 to initiate the first-in-human trial.

Emmanuel S. Antonarakis, MD

“I would like to congratulate the Acerand team, the research staff, and the first patient for helping us to reach this important milestone,” said principal investigator Emmanuel S. Antonarakis, MD, in the news release.¹ Antonarakis is the director of genitourinary oncology at the Masonic Cancer Center at the University of Minnesota, Minneapolis.

In total, the open-label phase 1 trial plans to enroll 67 adult patients across clinical trial sites in the US and Canada.³

Patients are eligible for enrollment if they have mCRPC with ongoing androgen deprivation therapy or have bilateral orchiectomy, an ECOG Performance Status of 0 or 1, a life expectancy of at least 6 months, and adequate organ and bone marrow function. Patients must have also underwent at least 1 prior line of therapy with a novel hormonal agent and taxane-based chemotherapy in the castration-resistant or hormone-sensitive setting.

The study is being conducted in 2 parts: a dose escalation and dose optimization phase. In phase 1, the investigators will assess the safety, tolerability, pharmacokinetic profile, and pharmacodynamics in patients following treatment with ACE-232. Phase 1 also seeks to establish a maximum tolerated dose, if applicable. In phase 2, patients with androgen receptor gene alterations will receive ACE-232 at 2 different dose levels with the goal of establishing the recommended phase 2 dose.

For the study, patients will receive ACE-232 tablets orally as a continuous regimen with dexamethasone and fludrocortisone (Florinef) until disease progression, unacceptable toxicity, or study withdrawal.

The primary end points for the study are the number of patients experiencing an adverse event (AE) or serious AE, the number of patients experiencing a dose-limiting toxicity, and the establishment of a maximum tolerated dose and recommended phase 2 dose. Secondary outcome measures include pharmacokinetic measures, prostate-specific antigen response, objective response rate, duration of response, radiographic progression-free survival, overall survival, and blood concentration of steroid hormone.

The investigators are also seeking to assess the association between gene aberrations in circulating tumor DNA and tumor response to treatment as an exploratory end point.

Final completion of the trial is expected in August 2028.

REFERENCES

1. Acerand Therapeutics initiates first-in-human phase I clinical trial of ACE-232, a novel CYP11A1 inhibitor for advanced prostate cancer. News release. Acerand Therapeutics. June 4, 2025. Accessed June 9, 2025. https://www.acerand.com/nw_20250604.html

2. Acerand announces promising ACE-232 preclinical data to be presented at the 2025 AACR Meeting. News release. Acerand Therapeutics. April 10, 2025. Accessed June 9, 2025. https://www.acerand.com/nw_20250410.html

3. Phase 1 study of ACE-232 to treat patients with metastatic castration-resistant prostate cancer. ClinicalTrials.gov. Last updated May 18, 2025. Accessed June 9, 2025. https://clinicaltrials.gov/study/NCT06801236