On December 21, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported receipt of U.S. Food and Drug Administration (FDA) permission for a Phase 1 study to proceed under the Company’s Investigational New Drug application (IND) for ON 123300, a proprietary, differentiated, first-in-class multi-kinase inhibitor (Press release, Onconova, DEC 21, 2020, View Source [SID1234573159]).

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"We are grateful to receive this timely, favorable response from the FDA to initiate a Phase 1 trial with ON 123300," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "We are advancing the process to secure Institutional Review Board approval, and affirm our expectation that the first patient will be enrolled during the first half of 2021."

The Phase 1 trial will be conducted in the U.S. and will assess the safety, tolerability and pharmacokinetics of ON 123300 administered orally as monotherapy at increasing doses starting at 40 mg daily or higher for consecutive 28-day cycles. The trial will enroll patients with relapsed/refractory advanced cancer, including but not limited to patients with HR+ HER2- metastatic breast cancer with clinical resistance to approved second-generation CDK4/6 inhibitors. Once the dose escalation phase of the trial is completed and the recommended Phase 2 dose is established, additional HR+ HER2- postmenopausal metastatic breast cancer patients resistant to approved second-generation CDK4/6 inhibitors will be enrolled. Additional patient cohorts are under consideration, including but not limited to patients diagnosed with advanced colorectal cancer, and non-Hodgkin’s lymphoma, in particular mantle cell lymphoma.

The design of this U.S. Phase 1 trial differs from the ongoing study with ON 123300 in China conducted by the Company’s partner HanX Biopharmaceuticals, Inc., which is dosing patients daily for 21 days. The HanX trial has enrolled four patients to date, has opened the second dosing cohort and is expected to continue enrolling patients with advanced cancer at two sites until the recommended Phase 2 dose is identified. Notably, of the three currently approved CDK4/6 inhibitors, two are approved for dosing in 21-day cycles and one is approved for dosing in a 28-day cycle. All three are blockbuster drugs marketed in HR+ HER2– metastatic breast cancer by well-known pharmaceutical companies, and all of these approved therapies require concomitant treatment with an aromatase inhibitor.

"Based on its differentiated mechanism of action, we believe that ON 123300 presents an innovative approach to study advanced cancers including in HR+ HER2- metastatic breast cancer that is or has become resistant to commercial CDK4/6 inhibitors. Beyond metastatic breast cancer, we believe that ON 123300 may present a novel approach to treating other cancers including mantle cell lymphoma, multiple myeloma, advanced colorectal cancer and hepatocellular carcinoma, as well as inoperable glioblastoma based on preclinical studies suggesting ON 123300 crosses the blood-brain barrier," added Richard Woodman, M.D, Chief Medical Officer.

About ON 123300

Onconova’s lead pipeline compound is the novel small molecule ON 123300, a proprietary, first-in-class multi-kinase inhibitor targeting tumor-driving kinases including CDK4/6 and ARK5. ON 123300 is reported to simultaneously inhibit both cell cycle and cellular energy metabolism through CDK4/6 and ARK5, respectively, and in vitro has been shown to be cytotoxic to cancer cells (killing the cancer cells). The current commercial CDK inhibitors are reported to be cytostatic (inhibiting the growth of cancer cells). With its differentiated mechanism of action, ON 123300 may present an innovative approach for treating solid tumors and hematologic malignancies that are refractory to or have become resistant to other CDK4/6 inhibitors. Based on experiments in preclinical models, ON 123300 exhibits single-agent cytotoxicity, and may have utility for certain types of cancers including breast cancer, non-Hodgkin’s lymphoma including mantle cell lymphoma, multiple myeloma, colorectal cancer, hepatocellular carcinoma, and inoperable glioblastoma.