EXL-01

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murine study suggests that the administration of EXL01 could reverse the resistance to ICI induced by antibiotics (unpublished data).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 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.

As treatment options are limited following progression on anti PD-(L)1 and platinum-based chemotherapy, we propose this trial for patients who have failed to respond or have shown intolerance to standard therapies or for whom no appropriate therapies are known to provide clinical benefit. Considering the strong therapeutic rationale of an association between antineoplastic immunotherapy and EXL01 (single-strain of F. prausnitzii, a bacteria which is a dominant member of the healthy gut microbiota), we propose to assess this combination for NSCLC treatment. This is a pilot, Phase I/II, one-arm, monocentric study evaluating the combination of EXL01 with nivolumab treatment for Non-Small Cell Lung Cancer patients.