Phase I Study of RNA Oligonucleotide, MTL-CEBPA, Atezolizumab and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma.

Advanced Hepatocellular Carcinoma Clinical Trial

Official title: A Phase 1 Study of RNA Oligonucleotide, MTL-CEBPA, Atezolizumab and Bevacizumab in Patients With Advanced Hepatocellular Carcinoma Without Previous Systemic Therapy.

Status Recruiting

Clinical Trial Summary

This is a single-center, phase 1, open label, dose-escalation study of MTL-CEBPA co-administered with atezolizumab and bevacizumab to assess the PK, PD, and potential toxicities of the drug combination in advanced HCC patients, and to determine the MTD, OBD or RP2D. The sample size employed is a minimally modified standard 3+3 cohort model commonly used in Phase I oncology studies. Once determined, the MTD/OBD/RP2D will be administered to an Expansion Cohort (Phase Ib) of 10 additional patients with advanced HCC.

Clinical Trial Description

Objectives and Study Endpoints

Study Objectives

1. Primary Objectives

• To determine the safety and tolerability of combination treatment MTL-CEBPA + atezolizumab + bevacizumab and determine the maximum tolerated dose (MTD) or optimum biologic dose (OBD), dose-limiting toxicities (DLTs), and recommended phase 2 dose (RP2D) for patients with advanced HCC.

• To determine the anti-tumor response using RECIST v1.1. of combination treatment MTL-CEBPA + atezolizumab + bevacizumab.

2. Secondary Objectives

• To assess the pharmacodynamics (PD) of combination treatment MTL-CEBPA + atezolizumab + bevacizumab notably on the effects on TIME (tumor immune microenvironment).

• To assess the pharmacokinetics (PK) of combination treatment MTL-CEBPA + atezolizumab + bevacizumab.

• To evaluate anti-tumour response using HCC modified RECIST (HCC mRECIST) and immune-modified RECIST (imRECIST) for combination treatment MTL-CEBPA + atezolizumab + bevacizumab in patients with advanced HCC.

Study Endpoints

1. Primary Endpoint

• Dose escalation part of the study (Phase 1a): the primary endpoint will be dose limiting toxicity (DLT) as defined in Section 4.4.2.

• Dose expansion part of the study (Phase 1b): the primary endpoint will be objective response rate (ORR) using RECIST v1.1 for a response duration of at least 6 weeks.

2. Secondary Endpoints

In phase 1a and 1b, the secondary endpoints are:

• The frequency of adverse events graded according to toxicity criteria (CTCAE v5.0) and categorized by body system and diagnosis.

• PK parameters defined by the maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), area under the plasma concentration curve (AUC) and the half-life of MTL-CEBPA after intravenous administration.

• Evaluation of changes in surrogate biomarkers, notably changes in levels of MDSCs

In phase 1b, additional secondary endpoints include:

• Progression free survival (PFS) defined as time from first dose of study drug to until progression or relapse, or death from any cause, whichever occurred first

• Overall survival (OS) defined as time from first dose of study drug until death from any cause.

3. Exploratory Endpoints

In phase 1a and 1b, exploratory endpoints are:

• Objective response rate (ORR) using HCC mRECIST and imRECIST.

• Changes from baseline of protein expression levels in blood and tumour tissue (including CEBPα and P21) as well as mRNA expression levels in blood (including CEBPA mRNA) will be evaluated.

• Changes in Tumour Mutational Burden (TMB) and PD-L1 status (biopsy samples) will both be assessed. ;

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

• NCT number: NCT05097911
• Study type: Interventional
• Source: National University Hospital, Singapore
• Contact: Cheng Ean Chee
• Phone: +65 6779 5555
• Email: cheng_ean_chee@nuhs.edu.sg
• Status: Recruiting
• Phase: Phase 1
• Start date: August 2, 2021
• Completion date: April 2027