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.
Objectives and Study Endpoints
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.
To assess the pharmacodynamics (PD) of combination treatment MTL-CEBPA +
atezolizumab + bevacizumab notably on the effects on TIME (tumor immune
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.
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.
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
CEBP and P21) as well as mRNA expression levels in blood (including CEBPA mRNA) will be
Changes in Tumour Mutational Burden (TMB) and PD-L1 status (biopsy samples) will both be
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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