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Prostate-specific antigen (PSA): A protein associated with the presence of prostate cancer in the body.
ECOG performance status: A system that measures a patient’s level of functioning, with 0 meaning patients are fully active.
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ONCT-534 Produces Tolerable Safety Outcomes in Relapsed/Refractory mCRPC
Key Takeaways
- ONCT-534 showed a well-tolerated safety profile in mCRPC patients on a twice-daily dosing schedule, with no grade 3 or higher toxicities reported.
- Despite trial discontinuation, ONCT-534 demonstrated potential in reducing PSA levels and target lesions in some patients.
Meta: ONCT-534 had a well-tolerated safety profile on a twice daily dosing schedule in relapsed/refractory metastatic castration-resistant prostate cancer.
ONCT-534, a dual-action AR inhibitor, showed a well-tolerated safety profile and potential clinical benefits in patients with relapsed/refractory mCRPC.
Treatment with the investigational, dual-action androgen receptor (AR) inhibitor, ONCT-534, elicited a well-tolerated safety profile when given to patients with relapsed/refractory metastatic castration-resistant prostate cancer (mCRPC) on a twice-daily dosing schedule, according to a press release from Oncternal Therapeutics, Inc — the drug’s manufacturer — which shared updated data from the phase 1/2 ONCT-534-101 trial.
“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 [twice-daily] dosing further, as well as studying ONCT-534 in earlier lines of therapy for advanced prostate cancer,” said Dr. James Breitmeyer, president and chief executive officer of Oncternal in the press release. “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.”
Based on initial pharmacokinetic results, a total of 15 patients were treated with ONCT-534 once daily in six dosing cohorts and six patients received ONCT-534 twice daily across two dosing cohorts of the phase 1/2 study. At a data cutoff of Sept. 30, 2024, the twice-daily dosing schedule was reported to be well tolerated and did not elicit grade 3 or higher toxicities.
Notably, one patient experienced a rising prostate-specific antigen (PSA) with ONCT-534 at the 160 milligram twice-daily dose and had a subsequent 50% reduction in PSA following four weeks of ONCT-534 given at 300 mg twice daily; a CAT scan also showed a 16% reduction in target lesions versus baseline.
Furthermore, notable effects on expression of AR-regulated genes, and AR nuclear translocation in six additional patients were seen following enumeration and biomarker analysis of circulating tumor cells. The circulating tumor cells analysis also showed that in patients who did not respond to ONCT-534, some had prostate cancer that had developed neuroendocrine features; these features are associated with AR-independent disease.
These findings come after the company reported in September 2024 that the ONCT-534-101 clinical trial was terminated following interim phase 1 findings which did not demonstrate clinically meaningful improvements in outcomes of patients treated across eight dose levels. However, the company did report that the agent was generally well tolerated.
Additionally, in October 2023, the FDA granted fast track designation to the agent for the treatment of patients with relapsed/refractory mCRPC who are resistant to other approved treatment options.
The press release went on the share that the investigational dual-action AR inhibitor ONCT-534 has demonstrated preclinical activity in prostate cancer models against unmutated AR, as well as against multiple forms of AR mutation and aberration. The drug’s manufacturer emphasized that this potential treatment for patients with mCRPC who present with unmet medical serves as a way to close the gaps that these patients experience in treatment. This is due to the agent’s resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain and splice variants with loss of the AR ligand binding domain.
The agent was investigated in the phase 1/2 trial which enrolled patients at least 18 years of age or older who presented with mCRPC and had no small cell features or neuroendocrine differentiation. Patients were eligible for the study if they had been previously treated for their relapsed/refractory disease with one or more next-generation AR-signaling inhibitors. These patients also must have at least one measurable lesion, an ECOG performance status of 0 to 2, and a life expectancy of at least six months.
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