SAN DIEGO, CA — Oncternal Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today updated the status of its dose escalation/dose expansion Phase 1/2 Study ONCT-808-101, evaluating the company’s ROR1-targeting autologous CAR T cell therapy ONCT-808 for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment.
At the initial dose of 1×106 CAR T cells per kg, two of the three patients achieved complete metabolic response (CMR) and the third achieved a partial response (PR) by FDG PET-CT. Common adverse events in this dosing cohort included decreased blood counts, pneumonia and Grade 1-2 cytokine release syndrome (CRS) as of a 4 December 2023 data cutoff.
The first patient treated at the second dose level of 3×106 CAR T cells per kg, an 80-year-old with bulky disease who had received four previous lines of therapy including CD19 CAR T, experienced a Grade 5 (fatal) serious adverse event consistent with CRS and immune effector cell-associated neurotoxicity syndrome (ICANS). No evidence of his lymphoma was found histologically, based on the patient’s initial autopsy report.
Oncternal has been in communication and is aligned with the Food and Drug Administration (FDA) on our proposed protocol changes that include modified eligibility criteria and testing lower doses of ONCT-808 for future patients in the study.
Salim Yazji M.D., Chief Medical Officer at Oncternal Therapeutics, commented, “The safety of every patient who participates in our studies is of the utmost priority for us. We believe these early disease response data indicate that ONCT-808 is a particularly potent autologous CAR T product with the potential to address significant unmet needs for patients with aggressive B-cell malignancies. With this clear path forward, we plan to implement the protocol amendment as rapidly as possible.”
About Oncternal Therapeutics
Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. Oncternal has initiated Study ONCT-534-101 (NCT05917470), which is open and enrolling patients for treatment with mCRPC. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced, compared with currently approved CAR T products. Oncternal has dosed patients under Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab has been evaluated in a Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 42 months in CLL patients expressing a p53 mutation/del(17p), a population underserved by current treatment options. Zilovertamab is also being evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905)
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