Oncternal Completes Enrollment and Begins Dosing for Sixth Cohort in Phase 1/2 Study of ONCT-534 for R/R Metastatic CRPC

On July 15, 2024, Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company specializing in novel oncology therapies, announced the completion of enrollment and the commencement of dosing for the sixth dose cohort in its Phase 1/2 study of ONCT-534. This study targets patients with metastatic castration-resistant prostate cancer (mCRPC) who have either relapsed or are resistant to approved androgen receptor pathway inhibitors (ARPIs).

In this sixth cohort, patients are administered ONCT-534, a dual-action androgen receptor inhibitor (DAARI), at a dosage of 1200 mg taken orally once daily. The progression to this higher dose followed a review of safety data from the fifth dose level, which was 600 mg daily, by the study’s Safety Review Committee (SRC). An initial update regarding the safety and efficacy of ONCT-534, focusing on prostate-specific antigen (PSA) levels, is anticipated in the third quarter of 2024 and will encompass data from the 1200 mg dose cohort.

Dr. Salim Yazji, Chief Medical Officer at Oncternal Therapeutics, expressed optimism about the rapid enrollment pace in the dose escalation segment of the Phase 1/2 study. He noted that ONCT-534 has been well tolerated with no dose-limiting toxicities observed, and there continues to be strong patient interest. Dr. Yazji also highlighted the anticipation of sharing preliminary safety and efficacy results, which will include comprehensive clinical and biomarker data as well as extended follow-up from earlier dosing cohorts.

The ONCT-534-101 study is designed as a Phase 1/2, single-arm, open-label, multi-center trial. Its main objectives are to assess the safety, tolerability, pharmacokinetics, and initial anti-tumor activity of ONCT-534 in mCRPC patients who have relapsed or are refractory to approved ARPIs such as enzalutamide, abiraterone, apalutamide, and darolutamide. Following the assessment of safety, tolerability, and preliminary anti-tumor activity in Phase 1, Phase 2 will commence to further evaluate these parameters to establish an optimal dose.

Oncternal Therapeutics is dedicated to developing innovative cancer treatments for patients with significant unmet medical needs. The company focuses on drug development targeting underexploited biological pathways involved in cancer progression, with a particular emphasis on hematological malignancies and prostate cancer. ONCT-534, a DAARI, has shown preclinical efficacy in prostate cancer models against both normal androgen receptors and various forms of androgen receptor aberrations. It holds promise for mCRPC patients who exhibit resistance to current ARPIs, including those with androgen receptor amplification, mutations in the ligand-binding domain (LBD), or splice variants lacking the AR LBD.

Additionally, ONCT-808 is an investigational CAR T cell therapy targeting ROR1, showing activity in preclinical models against various hematological malignancies and solid tumors. ONCT-808 is designed to specifically target cancer cells expressing ROR1. The company has developed an efficient manufacturing process aimed at reducing the waiting period for patients to receive their individualized CAR T therapy. Oncternal has begun dosing patients in the ONCT-808-101 study, which includes individuals with relapsed or refractory aggressive B-cell lymphoma who have not responded to previous CD19 CAR T treatments.

Zilovertamab, another investigational product, is a monoclonal antibody designed to inhibit ROR1 function. In combination with ibrutinib, it has shown promising results in a Phase 1/2 study for treating patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and marginal zone lymphoma (MZL), achieving 100% progression-free survival at 42 months in CLL patients with p53 mutations or del(17p). Zilovertamab is also under evaluation in an investigator-initiated Phase 1b study combined with docetaxel for metastatic castration-resistant prostate cancer.