Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma
NCT Number: NCT06551272
Acronym: MOTHER
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Hepatocellular Carcinoma
Interventions: DRUG: EXL01
Sponsor: Center Eugene Marquis
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 34
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SINGLE_GROUP|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-01
Completion Date: 2026-11-23
Locations: hôpital Avicenne, Bobigny, 93000, France|Hôpital Beaujon, Clichy, 92100, France|Centre de luttre contre le cancer Eugène Marquis, Rennes, 35000, France|Gustave ROUSSY, Villejuif, 94805, France

Summary:
Hepatocellular carcinoma (HCC) is the most common liver primary cancer with a high rate of mortality. Since the results of IMbrave150 (1), 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 (4).

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 (5-7). 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 (8,9). 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murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data).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 atezolizumab-bevacizumab for advanced HCC. We would include patients refractory to first-line treatment, and test the addition of EXL01 to atezolizumab-bevacizumab in order to reverse resistance.

Primary Outcome Measures: 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 Outcome Measures: Overall tumor response, Overall tumor response according to the mRECIST, RECIST 1.1 and iRECIST., At week6; at week12; at month 6, at month12|Objective Response Rate at week12, ORR at week 12 according to mRECIST and iRECIST criteria, at week 12|Objective Response Rate at M6 and M12, The ORR at M6, M12, according to the mRECIST, RECIST 1.1 and iRECIST criteria., At month 6, at month 12|The Disease control rate (DCR),, The Disease control rate (DCR), as the proportion of patients with BOR as CR, PR or stable disease (SD) defined according to the mRECIST, RECIST 1.1 and iRECIST criteria at W12, M6, M12., At week12; at month 6, at month12|The Progression-Free Survival, The Progression-Free Survival, defined as the time from patient inclusion to progression or death from any cause., Maximum 12 month after the fisrt EXL01 administration|Overall survival (OS), The Overall Survival, defined as the time from patient inclusion to death from any cause, Maximum 15 month after the fisrt EXL01 administration of the last patient