Phase 1/2 trial of ONCT-534 in mCRPC has been terminated

Oncternal Therapeutics has terminated its phase 1/2 ONCT-534-101 clinical trial (NCT05917470) evaluating ONCT-534 in patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC) that is resistant to current androgen receptor (AR) pathway inhibitors, the company announced in a news release.¹

Oncternal recently reported updated data from the twice-daily dosing cohorts in the trial.

ONCT-534 is an investigational dual action androgen receptor inhibitor. The therapy was previously granted a fast track designation by the FDA in October 2023 for this patient population.²

The decision to terminate the study was based on an interim readout from the trial, which showed that ONCT-534 did not lead to any clinically meaningful improvement of disease, including prostate-specific antigen (PSA) levels, in the 20 patients enrolled in the study. A dose-limiting toxicity was observed in 2 of 3 of the patients in the highest dose cohort of 1200 mg oral ONCT-534 once daily.

The company also made the decision to terminate its other phase 1/2 trial (NCT05588440) investigating ONCT-808 in patients with B-cell lymphoma.

“The early results during dose escalation in the phase 1/2 studies of ONCT-534 in heavily pretreated patients are disappointing, as the study was supported by extensive preclinical data and was designed to address important unmet medical needs for patients with advanced prostate cancer,” said James Breitmeyer, MD, PhD, Oncternal’s president and CEO, in the news release.¹ “In light of these data and the challenging financing environment, we intend to explore strategic options with the hope of advancing and realizing value from our pipeline including ONCT-534, ONCT-808, zilovertamab, and ONCT-216.”

The company recently unveiled updated data from the twice-daily dosing cohorts in the ONCT-534-101 trial,³ which were collected prior to the termination of the study. In total, 15 participants in the trial received ONCT-534 once daily across 6 dosing cohorts, and 6 patients received ONCT-534 twice daily (BID) across 2 dosing cohorts.

Updated data showed that 1 patient who had a PSA rise following treatment with 160 mg ONCT-534 BID experienced a subsequent PSA reduction of 50% following 4 weeks of treatment with 300 mg ONCT-534 BID. The patient also demonstrated a 16% reduction from baseline in target lesions, based on the follow-up CAT scan.

Regarding safety, no grade 3 or higher toxicities were reported.

The investigators also conducted an analysis of circulating tumor cells (CTCs) in 6 additional patients. Findings showed promising effects on the expression of AR-regulated genes and AR nuclear translocation. This analysis also showed that some patients who did not respond to treatment with ONCT-534 had prostate cancer that developed neuroendocrine features, which are linked with AR independent disease.

Based on these data, Breitmeyer concluded,³ “While we still believe the decision to discontinue the ONCT-534-101 clinical trial remains the correct one in the current biotechnology environment, the updated clinical results highlight the potential of ONCT-534 in prostate cancer. We believe there is value in exploring BID dosing further, as well as studying ONCT-534 in earlier lines of therapy for advanced prostate cancer. We continue to explore strategic alternatives for our product candidates, including ONCT-534, ONCT-808, zilovertamab and ONCT-216 in an ongoing effort to maximize value to our shareholders.”

References

1. Oncternal Therapeutics announces termination of its clinical studies and exploration of strategic alternatives. News release. September 12, 2024. Accessed November 7, 2024. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-announces-termination-its-clinical

2. 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 November 7, 2024. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-announces-fda-granted-fast-track

3. Oncternal Therapeutics announces updated safety and efficacy data for phase 1/2 study of ONCT-534 for the treatment of R/R metastatic castration-resistant prostate cancer. News release. October 22, 2024. Accessed November 7, 2024. https://investor.oncternal.com/news-releases/news-release-details/oncternal-therapeutics-announces-updated-safety-and-efficacy