FDA grants Fast Track Designation to ONCT-534 for mCRPC

The FDA has granted its Fast Track Designation to ONCT-534 for the treatment of patients with relapsed/refractory metastatic castration-resistant prostate cancer (mCRPC) that is resistant to androgen receptor pathway inhibitors (ARPIs), according to Oncternal Therapeutics, Inc, the developer of the novel dual-acting androgen receptor inhibitor.¹

To enroll, patients must have an ECOG performance status of 0, 1, or 2; serum testosterone less than 50 ng/dL; and a life expectancy of at least 6 months. A patient’s PSA level must be at last 10 ng/mL, or at least 2 ng/mL if they also have had at least a 50% increase from their lowest PSA level on prior therapy, whichever is lowest.

According Oncternal, “ONCT-534 interacts with both the N-terminal domain and the ligand-binding domain (LBD) of the androgen receptor (AR),” which both inhibits cell growth and leads to AR degradation. The company also reported that preclinical studies in prostate cancer mouse models have shown antitumor activity with ONCT-534 against unmutated AR, as well as against several AR alterations.¹

The FDA’s Fast Track designation is designed to expedite the review and development of novel treatments that will fill an unmet medical need.

“The receipt of Fast Track designation for ONCT-534 supports our belief that patients with mCRPC who relapse after treatment with ARPIs such as enzalutamide or abiraterone, represent an important unmet medical need,” James Breitmeyer, MD, PhD, Oncternal’s president and CEO, stated in a news release.¹

“We believe that due to ONCT-534’s novel mechanism of action, it may address important androgen receptor (AR) escape mechanisms that result in resistance to currently approved ARPIs. We look forward to working with FDA, investigators, and industry collaborators to bring ONCT-534 to patients as quickly as possible,” added Breitmeyer.

The open-label, single-arm, multicenter, phase 1/2 study is evaluating the efficacy, pharmacokinetics, and safety/tolerability of ONCT-534 in patients with mCRPC and relapsed/refractory disease after receiving treatment with 1 or more next-generation ARPIs, consisting of enzalutamide (Xtandi), abiraterone acetate (Zytiga), apalutamide (Erleada), and darolutamide (Nubeqa). The estimated enrollment for the trial is 59 patients.

To enroll, patients must have an ECOG performance status of 0, 1, or 2; serum testosterone less than 50 ng/dL; and a life expectancy of at least 6 months. A patient’s PSA level must be at last 10 ng/mL, or at least 2 ng/mL if they also have had at least a 50% increase from their lowest PSA level on prior therapy, whichever is lowest. Patients are not eligible to enroll if they have small cell prostate cancer or neuroendocrine disease histology, including mixed histology, or if they have brain or CNS metastases.²

In phase 1 of the trial patients will be assigned to specific dose levels. Based on the results with these dose levels, there will be 2 recommended dose levels chosen for phase 2.

The primary end points for the trial include determining maximum-tolerated dose, safety/tolerability, ≥50% PSA decline, ≥90% PSA decline, response, and progression-free survival.²

The estimated study completion date is January 31, 2028.²

References

1. Oncternal Therapeutics Announces FDA Granted Fast Track Designation for ONCT-534 for the Treatment of Metastatic Castration-Resistant Prostate Cancer. Published online October 26, 2023. Accessed October 28, 2023. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-announces-fda-granted-fast-track

2. NIH US National Library of Medicine ClinicalTrials.gov. A Clinical Study of ONCT-534 in Subjects With Metastatic Castration-resistant Prostate Cancer. ClinicalTrials.gov Identifier: NCT05917470. Last update posted October 23, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT05917470