Onconova Seeking FDA Approval for Phase 1 Trial of ON 123300 for Breast Cancer

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ON 123300 Phase 1 trial

Onconova Therapeutics is seeking the green light from the U.S. Food and Drug Administration (FDA) to begin a Phase 1 clinical trial for its small molecule ON 123300 in certain types of breast cancer.

The trial would include, but not be limited to, people with relapsed/refractory advanced breast cancer, including those with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative HER2-) metastatic breast cancer who are resistant to approved second-generation CDK4/6 inhibitors.

“Once the FDA approves our [investigational new drug application], 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,” Steven M. Fruchtman, MD, president and CEO of Onconova, said in a press release.

ON 123300 is a small molecule that works as a dual selective inhibitor of the CDK4/6 and ARK5 proteins. When overactive, CDK4/6 can lead to unregulated proliferation of cancer cells, and ARK5 is known to promote the survival of tumor cells in a nutrient-deprived environment.

In preclinical studies, ON 123300 was found capable of effectively killing cancer cells, rather than just slowing their proliferation, which is how currently marketed CDK inhibitors work.

“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,” Fruchtman said.

Enrolled participants will receive escalating doses of oral ON 123300, delivered daily at a starting dose at 40 mg, every 28 days, with the goal of assessing the therapy’s safety, tolerability, and pharmacokinetic profile, which refers to the movement of a medicine into, through, and out of the body. Moreover, the trial will also determine the best dose to continue clinical testing in a Phase 2 study.

Once the recommended Phase 2 dose is determined, the company also plans to enroll patients with advanced non-Hodgkin’s lymphoma, with a special focus on mantle cell lymphoma.

“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,” said Richard Woodman, MD, chief medical officer of Onconova.

A similar Phase 1 dose-escalation study for ON 123300 is currently ongoing in China. Launched in September by HanX Biopharmaceuticals, the trial has enrolled three patients to date.

Contrary to the U.S. trial, the Chinese study is dosing patients daily for 21 days. This is similar to the dosing schedule of two of the three currently approved CDK4/6 inhibitors — Ibrance (palbociclib) and Kisqali (ribociclib). The third, Verzenio (abemaciclib), is the only one approved for 28-day cycle dosing. Additionally, all approved CDK4/6 inhibitors are used in combination with hormone therapies.

“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,” Fruchtman said.

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