NCT06351644

ON 123300 (Narazaciclib) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

A Phase I/II Study to Assess the Safety and Tolerability of the Combination of Oral ON 123300 (Narazaciclib) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Adriana Rossi · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Multiple myeloma (MM) is a malignancy characterized by uncontrolled proliferation of plasma cells for which there is an urgent and unmet need to develop new, effective therapeutics. Onconova Therapeutics has developed a first-in-class oral inhibitor of CDK4 and ARK5 ON 123300 (NARAZACICLIB) which shows potent anti-myeloma activity in vitro and in vivo in preclinical models, and is undergoing evaluation in Phase 1-2 trials worldwide. In this study, the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 (NARAZACICLIB) in combination with dexamethasone in myeloma patients in a Phase I/II clinical trial.

Detailed description

ON 123300 (NARAZACICLIB) is a multi-targeted kinase inhibitor targeting cyclin-dependent kinases (CDK) 4 and 6, AMPK-related protein kinase 5 (ARK5), colony-stimulating factor 1 receptor (CSF1R), tyrosine-protein kinase kit (c-Kit), and fms-like tyrosine kinase (FLT)3 at low nM concentrations that can arrest the cell cycle and thus block tumor cell proliferation and inhibit the growth of cancer cells. As an apoptotic and antiproliferative agent, ON 123300 (NARAZACICLIB) modulates the levels and activities of regulatory proteins of the cell cycle, including cyclin D1 and inhibits retinoblastoma (Rb) protein binding. ON 123300 (NARAZACICLIB) inhibits cancer cell growth and suppresses deoxyribonucleic acid (DNA) synthesis by preventing CDK-mediated G1-S phase transition, followed by tumor cell death by induction of mitochondria-mediated apoptosis. ON 123300 (NARAZACICLIB) is being investigated for potential treatment of patients with solid tumors and hematologic malignancies as a single agent and in combination with other anticancer therapies. This is supported by antiproliferative and cytotoxic effects that have been observed with ON 123300 (NARAZACICLIB) in a wide variety of malignant human cell lines in cell-based assay systems, and in mouse xenograft models of breast cancer, colon cancer, mantle cell lymphoma, multiple myeloma, and melanoma. Based on the nonclinical efficacy models, Onconova intends to study patients with solid tumors and hematologic malignancies. As of the data cutoff date 05 January 2022, Onconova-sponsored Study 19-01 (United States \[US\]) is an ongoing exploratory Phase 1 dose escalation study to assess the safety, tolerability, and pharmacokinetics (PK) of ON 123300 (NARAZACICLIB) capsules administered orally as escalating daily doses in patients with advanced cancer relapsed or refractory to at least 1 prior line of therapy. Enrolled patients will continue 28-day cycles of ON 123300 (NARAZACICLIB) + dexamethasone as long as the drug shows anti-myeloma activity with a disease response ≥PR (PR, VGPR, CR) and the patient does not exhibit any DLTs and the study is open. Patients will continue the regimen until disease progression/intolerable toxicity/death, withdrawal OR for a maximum up to 2 years after enrollment. Treatment would be discontinued for Grade 4 or above toxicity. For Grade 2-3 toxicity, will challenge with the lower dose first before discontinuing. (Grading of toxicities per CTCAE version 5.0)

Conditions

• Relapsed and/or Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	ON 123300	dosed starting at 200 mg of ON 123300 (NARAZACICLIB) daily for four weeks. Dose levels will be 160 mg, 200 mg, 240 mg, 280 mg, 320 mg. Treatment cycles will be four weeks long. ON 123300 (NARAZACICLIB) is available as an oral formulation ON 123300 (NARAZACICLIB) monolactate capsules (containing 40 mg free base) and is provided in 120 cc high-density polyethylene (HDPE) bottles with child-resistant closures containing 30 hard gelatin capsules. ON 123300 (NARAZACICLIB) is also available in tablet form. The tablets are 40 mm (oblong) and 120 mg (round). Either form, capsules or tablets, may be used in this study.
DRUG	Dexamethasone	Weekly oral dexamethasone 20mg

Timeline

• Start date: 2024-10-02
• Primary completion: 2025-04-28
• Completion: 2025-04-28
• First posted: 2024-04-08
• Last updated: 2025-11-12

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study