Microbiota Modification for Immuno-oncology in Hepatocellular Carcinoma
Description
Atezolizumab-bevacizumab rechallenge after progression with the addition of the experimental treatment EXL01 - 1 capsule per day for a maximum of 12 months (EXL01 contains an unmodified single strain of F. prausnitzii)
Inclusion Criteria:
Male or female
Aged ≥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 atezolizumab plus bevacizumab combination
Decision made by the physician to continue atezolizumab plus bevacizumab beyond progression
Child-Pugh A within 7 days prior to inclusion
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
Exclusion Criteria:
Partial response achieved under atezolizumab-bevacizumab
CTCAE Grade ≥3 or more toxicity under atezolizumab-bevacizumab or persistent toxicity Grade >1
Liver involvement > 50%
Thromboembolic events in the 3 months prior to inclusion,
Presence of major macro vascular invasion (except Vp1/Vp2)
Prior bleeding event due to untreated or incompletely treated esophageal and / or gastric varices within 6 months' prior inclusion
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.
Note: Participants who have entered the follow-up phase of an investigational study may participate so long as it has been at least 3 months since the last dose of the previous investigational agent.
Has a systemic infection or other serious infection requiring systemic treatment within 30 days prior to screening.
Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products
Has a history of hypersensitivity to the atezolizumab or to any of the excipients listed in section 6.1 of the SmPC of atezolizumab
Has a history of hypersensitivity to bevacizumab or to any of the excipients listed in section 6.1 of the SmPC of bevacizumab
Has a history of hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies
Uncontrolled hypertension
Clinically significant cardiovascular disease such as pre-existing coronary artery disease, or congestive heart failure
Proteinuria
Has active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea, or other inflammatory disease requiring anti-inflammatory medications
Current probiotics administration, or planned probiotics administration during treatment course.
