Immunotherapy for Advanced Liver Cancer

NCT05033522 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: MBI-003-LIVE
• Study Type: interventional
• Target: 150
• Locations: 2 countries
• Sites: 8

Brief Summary

This is a randomized, controlled multi-site, multi-national clinical trial conducted in Thailand and Malaysia for Asian adults (males or females), 18 years of age and older presenting with advanced HCC (BCLC stage C) including subjects with macrovascular involvement and/or extrahepatic spread (not eligible for TACE, surgery or locoregional treatment) with Child-Pugh stage A or B liver function. 150 subjects will be randomized 2:1 to AlloStim® immunotherapy vs Physician's Choice of Sorafenib, Lenvatinib or FOLFOX4.

Conditions

Hepatocellular Carcinoma

Keywords

liver cancer; immunotherapy; Thailand; Malaysia

Outcome Measures

Primary Outcomes (1)

• overall survival

  the time from randomization till death

  rom date of randomization until the date of death from any cause, assessed up to 48 months

Secondary Outcomes (2)

• Quality of Life Survey

  weekly assessments from baseline to 28 weeks

• Time to Symptomatic Progression

  rom date of randomization weekly for up to 24 weeks until the date of first documented progression which ever comes first

Study Arms (2)

AlloStim®

EXPERIMENTAL

AlloStim® is a formulation of living allogeneic Th1-like cells with anti-CD3/CD28 microbeads attached derived from precursors purified from healthy screened blood donors that are differentiated and expanded ex-vivo. AlloStim® is formulated at 10-7 cells/ml in 0.5ml for ID administration and 3ml for IV administration

Biological: AlloStim® immunotherapy

Physician's Choice

ACTIVE COMPARATOR

Physician's Choice is sorafenib or levantinib or FOLFOX4 monotherapy

Drug: FOLFOX regimen; Drug: Sorafenib; Drug: Lenvatinib

Interventions

AlloStim® immunotherapy BIOLOGICAL

3 cycles of intradermal and intravenous administrations

AlloStim®

FOLFOX regimen DRUG

Comparative arm: Physician Choice of FOLFOX4 chemotherapy

Also known as: Physician Choice FOLFOX4

Physician's Choice

Sorafenib DRUG

Comparative arm: Physician Choice of Sorafenib

Also known as: Sorafenib Physician's Choice

Physician's Choice

Lenvatinib DRUG

Comparative Arm: Physician's Choice of Levantinib

Also known as: Levantinib Physician's Choice

Physician's Choice

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females who are at least 18 years of age at time of enrollment
• Histologically or cytologically documented advanced HCC (BCLC stage C) disease at diagnosis.
• No prior treatment for BCLC class C disease.
• Child-Pugh Class A or subset of Child-Pugh Class B
• Performance status: ECOG \< 2 with no deterioration over the previous 2 weeks
• With or without positive HBV and/or HCV
• With or without extrahepatic disease and with or without macrovascular invasion
• Measurable enhancing disease in liver with at least one target lesion evaluable by mRECIST
• Adequate hematological, liver and renal function as assessed by the following:
• Hemoglobin \> 10.0 g/dl
• Platelet count \> 75,000/μl
• ALT and AST \< 5.0 x ULN
• Serum creatinine \< 1.5
• Women of child-bearing potential: negative pregnancy test
• Patients of child producing potential: usage of contraception or avoidance of pregnancy measures while enrolled on study

You may not qualify if:

• Any prior cancer diagnosis (other than cured basal cell carcinoma, head and neck carcinoma in-situ, or superficial Ta, Tis, T1 bladder cancer) or concurrent cancer histologically different than HCC (e.g., cholangiocarcinoma).
• Child-Pugh liver function combined score \>9 (Class C or Class D)
• Moderate uncontrolled or severe ascites (+3 on Child-Pugh calculator)
• Clinical symptoms of hepatic decompensation or presence of hepatic encephalopathy
• Severe stomach/esophageal varices requiring interventional treatment.
• Unable to tolerate radiological contrast dye
• Any prior experimental, approved or off-label treatment for HCC (including levantinib, nivolumab, duvalumab, tremelimumab, brivananib, cabozantinib or ramucircumab) or any approved or experimental procedures such as surgery, radiation or ablation.
• Enrollment in any previous clinical trial for HCC
• Any history of autoimmune disorder (type I, insulin-dependent diabetes allowed)
• History of COPD or oxygen saturation \<92% at room air
• Any clinical condition requiring systemic steroids (inhaled steroids allowed) or any current immunosuppressive therapy or anti-epileptic drug therapy.
• Known history of HIV infection
• Clinically significant gastrointestinal bleeding within 30 days prior to study entry
• History of cardiac disease: congestive heart failure \> NYHA class 2; cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or Digoxin are permitted)
• Uncontrolled hypertension (SBP \>150 or DBP\>90).

Sponsors & Collaborators

• Mirror Biologics, Inc.: lead
• Immunovative (Thailand) Co., Ltd: collaborator

Study Sites (8)

Sultan Ismail Hospital

Johor Bahru, Johor, 81100, Malaysia

Location

Sultanah Bahiyah Hospital

Alor Star, Kedah, 05460, Malaysia

Location

Columbia Asia Bukit Rimau

Shah Alam, Selangor, 40460, Malaysia

Location

Siriraj Hospital

Bangkok Noi, Bangkok, 10700, Thailand

Location

Prince of Songkla University (Songklanagarind Hospital)

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Naresuan University Hospital

Phitsanulok, Tha Pho, 65000, Thailand

Location

Chiangmai University

Chiang Mai, Thailand

Location

Songklanagarind Hospital

Khon Kaen, Thailand

Location

Related Links

• sponsor website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Interventions

Folfox protocol; Sorafenib; lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The investigator and subjects will be informed of the treatment group to which the subject has been randomized.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects are randomized 2:1 to experimental vs physician's choice. A two-sided logrank test with an overall sample size of 130 subjects (43 in the control group and 87 in the treatment group) achieves 80% power to detect at a 0.05 significance level a hazard ratio of 0.56 when the control group median survival is 6.5 months. A total of 150 subjects are planned to be accrued.

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 2, 2021
• Study Start: August 1, 2023
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: October 23, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

MY (3); TH (5)