Oncternal Reports New Phase 1/2 Data on ONCT-534 for Metastatic Castration-Resistant Prostate Cancer

Oncternal Therapeutics, Inc. (Nasdaq: ONCT) revealed new findings from its Phase 1/2 clinical trial of ONCT-534, which targets patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC). The updated data includes promising results from a revised dosing schedule.

The Phase 1/2 study incorporated twice daily (BID) oral dosing of ONCT-534, involving a total of 21 patients. Fifteen patients received the drug once daily (QD) in six different dose levels, while six patients were given BID doses across two cohorts. As of September 30, 2024, the BID dosing regimen appeared to be well tolerated with no reports of Grade 3 or higher toxicities. Notably, one patient who initially had an increasing PSA at 160 mg BID experienced a 50% reduction in PSA levels after four weeks on 300 mg BID dosage. Additionally, a CAT scan indicated a 16% decrease in target lesions for this patient.

The analysis of circulating tumor cells (CTCs) in six additional patients showed encouraging impacts on the expression of androgen receptor (AR)-regulated genes and AR nuclear movement. It was also found that certain patients who did not respond to ONCT-534 had prostate cancer displaying neuroendocrine features, which are typically linked to AR-independent disease.

Dr. James Breitmeyer, Oncternal's President and CEO, commented on the updated clinical results, acknowledging the potential of ONCT-534 for treating prostate cancer. He noted that while discontinuing the ONCT-534-101 clinical trial was a reasonable decision in the current biotech landscape, the new data underscores the value of continuing to explore BID dosing and investigating ONCT-534's efficacy in earlier treatment stages for advanced prostate cancer.

Oncternal Therapeutics is a biopharmaceutical company in the clinical stage, dedicated to developing innovative cancer treatments, particularly for patients with significant unmet needs. The company focuses on targeting novel biological pathways critical to cancer progression, including hematological malignancies and prostate cancer.

ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) that has shown preclinical activity in prostate cancer models. It targets both unmutated androgen receptors and various mutants and aberrations of AR. This drug holds potential for mCRPC patients resistant to conventional androgen receptor pathway inhibitors, including those with specific AR mutations or amplifications.

Other products in Oncternal's pipeline include ONCT-808, an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets ROR1 using zilovertamab's binding domain. ONCT-808 has demonstrated efficacy in preclinical models against several hematological malignancies and solid tumors, showing specificity for cancer cells expressing ROR1.

Zilovertamab, another investigational monoclonal antibody from Oncternal, is designed to inhibit ROR1 function. It has been evaluated in combination with ibrutinib for treating mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL). It has also received Orphan Drug Designation from the U.S. FDA for CLL and MCL.

ONCT-216, previously known as TK216, is an investigational small-molecule inhibitor targeting the ETS family of oncoproteins. It has shown promise in preclinical models for treating Ewing sarcoma and other tumors involving ETS-related translocations. The U.S. FDA has granted ONCT-216 Rare Pediatric Disease Designation, Orphan Drug Designation, and Fast Track Status for Ewing sarcoma.

These updates reflect Oncternal's commitment to developing effective cancer treatments and exploring strategic alternatives for its product candidates to maximize shareholder value.