On November 23, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the filing of an Investigational New Drug application (IND) with the U.S. Food and Drug Administration (FDA) for ON 123300, the Company’s proprietary, differentiated, first-in-class multi-kinase inhibitor (Press release, Onconova, NOV 23, 2020, View Source [SID1234571568]). The IND seeks permission to begin a Phase 1 trial with ON 123300 in relapsed/refractory advanced cancer including patients with HR+ HER 2- metastatic breast cancer with resistance to approved second-generation CDK4/6 inhibitors.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"We believe that ON 123300, based on its novel mechanism of action, presents an innovative approach to study advanced cancers including in HR+ HER 2- metastatic breast cancer that is or has become resistant to commercial CDK4/6 inhibitors. We are delighted to have filed our IND on schedule, and look forward to enrolling patients in the U.S. to complement the ongoing Phase 1 dose-escalation study underway in China by our partner HanX Biopharmaceuticals," said Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova. "The HanX Phase 1 ON 123300 study, which began in September 2020, has enrolled three patients to date and is expected to continue to enroll patients with advanced relapsed/refractory cancer at two sites until the recommended Phase 2 dose is identified. We believe that data from these two studies will generate important information to inform anticipated later-stage studies."
As currently envisioned, the Phase 1 trial in the U.S. 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 Phase 1 trial is planned for patients with relapsed/refractory advanced cancer, including but not limited to patients with HR+ HER 2- metastatic breast cancer with clinical resistance to the approved second-generation CDK4/6 inhibitors. Once the recommended Phase 2 dose is established, the Company’s plan is to enroll additional HR+ HER 2- postmenopausal metastatic breast cancer patients refractory to approved second-generation CDK4/6 inhibitors, as well as patients diagnosed with advanced non-Hodgkin’s lymphoma with a special interest in mantle cell lymphoma.
This trial design in the U.S. differs from the study in China because HanX is dosing patients daily for 21 days. 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 by well-known pharmaceutical companies, and all of these approved therapies require concomitant treatment with an aromatase inhibitor.
"Beyond metastatic breast cancer, we believe that ON 123300 may present an innovative approach to treating other cancers including mantle cell lymphoma, multiple myeloma, advanced colorectal cancer, advanced hepatocellular carcinoma, and inoperable glioblastoma based on preclinical studies suggesting ON 123300 crosses the blood-brain barrier," added Richard Woodman, M.D, Chief Medical Officer.
Commenting on the expected timetable and next steps with this program, Dr. Fruchtman added: "Once the FDA approves our IND, we will seek Institutional Review Board approval at the site where this Phase 1 trial will be conducted. We anticipate the first patient to be enrolled during the first half of 2021. With the ON 123300 program advancing, investigator-sponsored trials underway with our pipeline product rigosertib, and an active business development campaign to evaluate additional compounds, we look forward to an expanding portfolio of novel therapeutics for large, underserved oncology indications."
About ON 123300
Onconova’s lead pipeline product 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) rather than just cytostatic (inhibiting the growth of cancer cells), which is how the currently commercial CDK inhibitors are reported to work. 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, may have utility for certain types of cancers including breast cancer and non-Hodgkin’s lymphoma, and may also have utility for mantle cell lymphoma, multiple myeloma, advanced colorectal cancer, advanced hepatocellular carcinoma, and inoperable glioblastoma.