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

NCT05097911 | Active Not Recruiting Phase 1

• 1 other identifier: 2020/00223
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Hepatocellular Carcinoma

Keywords

MTL-CEBPA; Atezolizumab; Bevacizumab

Outcome Measures

Primary Outcomes (2)

• Evaluable for Objective Response

  Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response (using RECIST v1.1)

  5 years

• Evaluable Non-Target Disease Response

  Patients who have lesions present at baseline that are evaluable but do not meet the definitions of measurable disease, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for non-target lesion assessment. The response assessment is based on the presence, absence, or unequivocal progression of the lesions.

  5 years

Secondary Outcomes (2)

• Measurable Disease

  5 years

• Evaluation of Best Overall Response

  5 years

Study Arms (1)

Advanced HCC patients

EXPERIMENTAL

Patients will receive treatment as outlined until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, and clinical status. If scheduled dosing and study assessments are precluded because of a holiday, weekend, or other event, then dosing may be postponed to the soonest following date, with subsequent dosing continuing on a 21-day schedule. If treatment was postponed for fewer than 3 days, the patient can resume the original schedule.

Drug: MTL-CEBPA; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

MTL-CEBPA DRUG

The starting dose will be at dose level 1. For cycle 1 only, there will be a lead-in period whereby patients will receive one dose of MTL-CEBPA, 7 days prior to cycle 1 day 1. MTL-CEBPA is then administered on Day 1 and 8 of each cycle, atezolizumab is administered on Day 1 of each cycle and bevacizumab is administered on Day 1 of each cycle. One cycle of treatment consists of 21 days.

Advanced HCC patients

Atezolizumab DRUG

The starting dose will be at dose level 1. For cycle 1 only, there will be a lead-in period whereby patients will receive one dose of MTL-CEBPA, 7 days prior to cycle 1 day 1. MTL-CEBPA is then administered on Day 1 and 8 of each cycle, atezolizumab is administered on Day 1 of each cycle and bevacizumab is administered on Day 1 of each cycle. One cycle of treatment consists of 21 days.

Advanced HCC patients

Bevacizumab DRUG

The starting dose will be at dose level 1. For cycle 1 only, there will be a lead-in period whereby patients will receive one dose of MTL-CEBPA, 7 days prior to cycle 1 day 1. MTL-CEBPA is then administered on Day 1 and 8 of each cycle, atezolizumab is administered on Day 1 of each cycle and bevacizumab is administered on Day 1 of each cycle. One cycle of treatment consists of 21 days.

Advanced HCC patients

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Age ≥ 21 years
• Life expectancy \>3 months
• Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS) score of 0 or 1
• Histologically confirmed metastatic and/or unresectable HCC with cirrhosis resulting from hepatitis B, hepatitis C, alcohol-related liver disease or any other aetiology OR Histologically confirmed metastatic and/or unresectable HCC with or without cirrhosis
• Child-Pugh class A
• Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
• No prior systemic therapy (including systemic investigational agents) for HCC
• At least one measurable (per RECIST v1.1) untreated lesion
• Patients who received prior local therapy (e.g., radiofrequency ablation, percutaneous ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, transarterial chemoembolization, transarterial embolization, etc.) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST version 1.1.
• Acceptable laboratory parameters, as demonstrated by:
• Platelets ≥ 75 x 109/L
• Serum albumin ≥ 28 g/L
• ALT and AST ≤ 5 x ULN
• Bilirubin ≤ 3 x ULN

You may not qualify if:

• Child-Pugh class B or C
• Patients who have been treated with loco-regional therapy within the last 28 days prior to study treatment initiation
• Major surgery within the last 28 days prior to study treatment initiation
• Any systemic therapy or investigational agent in the advanced setting within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies or treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL-2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment.
• Grade \> 1 prior treatment-related toxicity (excluding alopecia) at the time of screening
• Use of filgrastim or peg-filgrastim 14 days prior to study entry
• Patients with clinically significant cancer ascites
• Any episode of bleeding from oesophageal varices or other uncontrolled bleeding within the last 6 months prior to study treatment initiation
• Patients administered with serum albumin within the last 7 days prior to the first study drug administration
• Known infection with human immunodeficiency virus (HIV)
• Known active tuberculosis (TB)
• Leptomeningeal metastasis
• Symptomatic brain metastases. Asymptomatic patients with treated brain metastases are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

Related Publications (2)

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005 Mar-Apr;55(2):74-108. doi: 10.3322/canjclin.55.2.74.

  PMID: 15761078 BACKGROUND

MeSH Terms

Interventions

atezolizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Cheng Ean Chee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: October 28, 2021
• Study Start: August 2, 2021
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: September 23, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)