SAN DIEGO, CA, USA I August 03, 2023 I Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced the receipt of a Study May Proceed letter from the U.S. Food and Drug Administration (FDA), for a Phase 1/2 dose escalation study of ONCT-534, a novel dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs). The letter was received prior to the 30-day review date.
“We are very pleased with the FDA’s authorization to proceed with our Phase 1/2 clinical trial of ONCT-534,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “Many men suffering from prostate cancer that has relapsed or is refractory after treatment with standard of care ARSI therapy, such as enzalutamide or abiraterone, need additional treatment alternatives. We believe that ONCT-534’s novel mechanism of action may help address key tumor escape mechanisms that cause such resistance. Preclinical studies suggest that ONCT-534 binds to both the ligand-binding domain (LBD) and N-terminal domain of the androgen receptor (AR), inhibiting AR function and triggering AR protein degradation, even in the presence of ligand-binding domain alterations including mutations and splice variants such as AR-V7. Clinical sites that will conduct the initial dose finding study for ONCT-534 have been selected and we expect to report preliminary data in the first half of 2024”.
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-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. Oncternal has initiated Study ONCT-808-101 (NCT05588440) for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. 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 product to be produced, compared with approved CAR T products. ONCT-534 is a 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 aberrations. It is a potential treatment for patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC) and 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. ONCT-534 has an active U.S. IND, and a Phase 1/2 clinical trial is being opened. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab showed evidence of antitumor activity and was well tolerated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma, chronic lymphocytic leukemia (CLL) and marginal zone lymphoma. Zilovertamab is being evaluated in two investigator-initiated studies: a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory (R/R) CLL (NCT04501939), and a Phase 1b study of zilovertamab in combination with docetaxel in patients with mCRPC (NCT05156905). More information on our company and programs is available at https://oncternal.com/.
SOURCE: Oncternal Therapeutics
Post Views: 241
SAN DIEGO, CA, USA I August 03, 2023 I Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, today announced the receipt of a Study May Proceed letter from the U.S. Food and Drug Administration (FDA), for a Phase 1/2 dose escalation study of ONCT-534, a novel dual-action androgen receptor inhibitor (DAARI), in patients with metastatic castration-resistant prostate cancer (mCRPC) who have relapsed or are refractory to approved androgen receptor signaling inhibitors (ARSIs). The letter was received prior to the 30-day review date.
“We are very pleased with the FDA’s authorization to proceed with our Phase 1/2 clinical trial of ONCT-534,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “Many men suffering from prostate cancer that has relapsed or is refractory after treatment with standard of care ARSI therapy, such as enzalutamide or abiraterone, need additional treatment alternatives. We believe that ONCT-534’s novel mechanism of action may help address key tumor escape mechanisms that cause such resistance. Preclinical studies suggest that ONCT-534 binds to both the ligand-binding domain (LBD) and N-terminal domain of the androgen receptor (AR), inhibiting AR function and triggering AR protein degradation, even in the presence of ligand-binding domain alterations including mutations and splice variants such as AR-V7. Clinical sites that will conduct the initial dose finding study for ONCT-534 have been selected and we expect to report preliminary data in the first half of 2024”.
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-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. Oncternal has initiated Study ONCT-808-101 (NCT05588440) for the treatment of patients with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. 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 product to be produced, compared with approved CAR T products. ONCT-534 is a 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 aberrations. It is a potential treatment for patients with relapsed or refractory metastatic castration-resistant prostate cancer (mCRPC) and 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. ONCT-534 has an active U.S. IND, and a Phase 1/2 clinical trial is being opened. Zilovertamab is an investigational monoclonal antibody designed to inhibit the function of ROR1. Zilovertamab showed evidence of antitumor activity and was well tolerated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma, chronic lymphocytic leukemia (CLL) and marginal zone lymphoma. Zilovertamab is being evaluated in two investigator-initiated studies: a Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory (R/R) CLL (NCT04501939), and a Phase 1b study of zilovertamab in combination with docetaxel in patients with mCRPC (NCT05156905). More information on our company and programs is available at https://oncternal.com/.
SOURCE: Oncternal Therapeutics
Post Views: 241
