Oncternal Therapeutics announced updated data from its Phase 1/2 study of ONCT-534, an investigational dual-action androgen receptor inhibitor (DAARI), for the treatment of patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC). The data, from the ONCT-534-101 trial (NCT05917470), suggests potential benefits of twice-daily (BID) dosing. While the company previously decided to discontinue the trial, these results highlight the drug's potential in prostate cancer treatment.
Updated Clinical Results
The Phase 1/2 study incorporated two additional dosing cohorts with twice-daily oral dosing of ONCT-534 based on initial pharmacokinetic results. Fifteen patients received ONCT-534 once daily (QD) and six patients received it BID. Data cutoff was September 30, 2024. The BID dosing schedule was well-tolerated, with no related Grade 3 or higher toxicities reported. Notably, one patient who experienced a rising PSA level on ONCT-534 at 160 mg BID, subsequently achieved a 50% reduction in PSA after four weeks of treatment with ONCT-534 at 300 mg BID. A CAT scan also revealed a 16% reduction in target lesions compared to baseline in the same patient.
Biomarker Analysis
Enumeration and biomarker analysis of circulating tumor cells (CTCs) showed promising effects on the expression of androgen receptor (AR)-regulated genes and AR nuclear translocation in six additional patients. Further CTC analysis indicated that some patients who did not respond to ONCT-534 had prostate cancer that had developed neuroendocrine features, which are associated with AR-independent disease.
Future Directions
"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," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "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."
Oncternal continues to explore strategic alternatives for its product candidates, including ONCT-534, ONCT-808, zilovertamab, and ONCT-216, to maximize value to its shareholders.
