Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma

NCT06551272 | Recruiting Phase 2 DMC

• 1 other identifier: 2023-1-69-001
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

Brief Summary

Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150, immunotherapy have emerged as a standard of care for HCC patients advanced and/or unresectable in first line of treatment. The objective response rate was about 30%, but half of patients would present only stable disease and about 20% progressive disease. Faecalibacterium prausnitzii is one of the most abundant bacterial in human gut microbiota, around 5% of total bacteria in feces. For patients with metastatic melanoma, treated with ipilimumab, an antibody targeting CTLA-4 (Cytotoxic T-lymphocyte-associated antigen 4), patients with a baseline gut microbiota enriched with Faecalibacterium had a significantly better clinical outcomes. In patients with metastatic melanoma, the level of Faecalibacterium prausnitzi at baseline was predictive of response to anti-PD-1 (programmed death-1) or anti-CTLA-4 therapy. EXL01 is a pharmacological preparation of Faecalibacterium prausnitzii strains. Preclinical murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data). We thus plan to test the concept of microbiota modification in patients treated with standard-of-care approved first-line immunotherapy for advanced HCC. We would include patients refractory to first-line treatment, and test the addition of EXL01 to standard-of-care approved first-line immunotherapy in order to reverse resistance.

Conditions

Hepatocellular Carcinoma

Keywords

Immunotherapy; microbiome; resistance; dysbiosis; Faecalibacterium prausnitzii

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate at week12

  ORR defined as the best observed overall tumor response (BOR) from inclusion to W12, according RECIST 1.1 criteria

  At week12

• Adverse event

  safety of atezolizumab-bevacizumab with bacterial supplementation EXL01

  Maximum 15 month after le first EXL01 administration

Secondary Outcomes (6)

• Overall tumor response

  At week6; at week12; at month 6, at month12

• Objective Response Rate at week12

  at week 12

• Objective Response Rate at M6 and M12

  At month 6, at month 12

• The Disease control rate (DCR),

  At week12; at month 6, at month12

• The Progression-Free Survival

  Maximum 12 month after the fisrt EXL01 administration

Study Arms (1)

standard-of-care approved first-line immunotherapy- EXL01

EXPERIMENTAL

Patients treated with atezolizumab-bevacizumab ou durvalumab with the addition of the experimental treatment exl01, 1 capsule per day for a maximum of 12 months.

Drug: EXL01

Interventions

EXL01 DRUG

EXL01 contains an unmodified single strain of F. prausnitzii

standard-of-care approved first-line immunotherapy- EXL01

Eligibility Criteria

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

You may qualify if:

• Male and Female
• Age ≥18 years at time of signing informed consent
• Presenting with HCC, diagnosed either by histological or radiological criteria as described by EASL
• Locally advanced or metastatic and/or unresectable HCC according a Multidisciplinary Team meeting
• Progressive disease after exposure to standard-of-care approved first-line immunotherapy
• Decision made by the physician to continue the same standard-of-care approved first-line immunotherapy beyond progression
• ECOG performance status 0 to 1
• Adequate hematological (Hemoglobin \>8.5g/dL, platelets \>60G/L, neutrophils \>1.5G/L) and renal (creatinine clearance \> 50 mL/min according to Cockcroft or MDRD formula) functions
• Disease measurable by RECIST 1.1
• Signed written Informed consent

You may not qualify if:

• Partial response achieved under standard-of-care approved first-line immunotherapy
• CTCAE Grade ≥3 or more toxicity under standard-of-care approved first-line immunotherapy, or persistent toxicity Grade \>1
• Liver involvement \> 50%
• Presence of major macro vascular invasion (except Vp1/Vp2)
• Pregnant woman, or breastfeeding or women of child-bearing potential with no adequate contraception (see §4.3.1)
• Under curatorship, guardianship, safeguard of justice or deprived of liberty
• History of serious autoimmune disease
• Interstitial lung disease
• HBV chronic infection with HBV DNA \> 100 IU/mL or without antiviral therapy; HBV patients with cirrhosis should be treated
• HIV infection
• Immunosuppression, including subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg/day prednisone equivalent)
• Transplanted liver, or patient with intent for transplantation
• Has difficulties in swallowing.
• Has undergone major surgery or significant trauma ≤4 weeks prior to Screening. Note: Participants who had surgery \>4 weeks prior to Screening must have recovered adequately from any toxicity and/or complications from the surgery or trauma prior to starting study intervention.
• Is currently participating in or has participated in a study with an investigational compound or device within 3 months prior to the first dose of study intervention.

Sponsors & Collaborators

• Center Eugene Marquis: lead

Study Sites (6)

hôpital Avicenne

Bobigny, 93000, France

ACTIVE NOT RECRUITING

CHU de Bordeaux

Bordeaux, France

ACTIVE NOT RECRUITING

Hôpital Beaujon

Clichy, 92100, France

RECRUITING

CHU de Nantes Hotel Dieu

Nantes, 44 000, France

ACTIVE NOT RECRUITING

Centre de luttre contre le cancer Eugène Marquis

Rennes, 35000, France

RECRUITING

Gustave ROUSSY

Villejuif, 94805, France

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Dysbiosis

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Héloise BOURIEN, Dr

  Centre de lutte contre le cancer Eugène Marquis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valérie JOLAINE

CONTACT

0299253036; v.jolaine@rennes.unicancer.fr

Marion TROCHET

CONTACT

m.trochet@rennes.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2024
• First Posted: August 13, 2024
• Study Start: March 12, 2025
• Primary Completion: March 12, 2026
• Study Completion (Estimated): December 12, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)