MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A...

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• CCAAT/enhancer-binding protein alpha (C/EBP-α) is crucial for liver and myeloid cell functions and cancer development.
• MTL-CEBPA is a pioneering small activating RNA (saRNA) drug designed to increase C/EBP-α levels.

Purpose of the Study:

• To evaluate the safety and efficacy of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC).
• To determine the maximum tolerated dose and optimal dosing schedule for MTL-CEBPA.

Main Methods:

• A Phase I, open-label, dose-escalation study (3+3 design) was conducted.
• Adults with advanced HCC received intravenous MTL-CEBPA weekly for 3 weeks, followed by a 1-week rest period.
• Patients were assessed for safety and efficacy endpoints.

Main Results:

• Thirty-eight participants received MTL-CEBPA across various doses (28-160 mg/m²).
• No dose-limiting toxicities were observed, indicating an acceptable safety profile.
• In evaluable HCC patients, one achieved a partial response (4%) and 12 had stable disease (50%).
• A subset of patients later treated with tyrosine kinase inhibitors (TKIs) showed promising responses.

Conclusions:

• MTL-CEBPA is the first saRNA to enter clinical trials, demonstrating a favorable safety profile in HCC patients.
• The drug shows potential for synergistic efficacy when combined with TKIs.
• Phase I results support further investigation of MTL-CEBPA, including combination studies with sorafenib for HCC treatment.