Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab (FLORA)

Prior treatment

• Use of immunosuppressive medication within 6 months prior to the first dose of Atezolizumab / Bevacizumab.
• Active or prior documented autoimmune or inflammatory disorders
• Prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-VEGF antibodies.
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow a formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism or excretion of investigational product.
• Usage of systemic antibiotic therapy within 2 weeks prior to the first dose of Atezolizumab/Bevacizumab.
• Usage of probiotic products/supplements within 1 week prior to the first dose of Atezolizumab/Bevacizumab.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention.

Other illness

• Known to have tested positive for human immunodeficiency virus (HIV) infection.
• Co-infection of HBV and HCV. Subjects with a history of HCV infection but who are negative for HCV RNA by PCR will be considered non-infected with HCV.
• Evidence by investigator assessment of varices at risk of bleeding on upper endoscopy undertaken within 12 months of randomization.
• Uncontrolled arterial hypertension defined by a systolic pressure \> 150 mm Hg or diastolic pressure \> 90 mm Hg or other hypertensive cardiovascular complications despite standard medical treatment.
• Any history of nephrotic or nephritic syndrome.
• History of another primary malignancy.
• History of hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product.
• Known hypersensitivity to any component of the vancomycin, atezolizumab or bevacizumab formulation.

Other

• Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC, or mixed cholangiocarcinoma and HCC.
• Pregnancy or lactation.
• Participation in other interventional clinical trials or observation period of competing clinical trials, respectively.
• Held in an institution by legal or official order.
• Legally incapacitated.

• Age 18 years or older
• Confirmed radiologic or histological diagnosis of HCC
• Disease not amenable to resection, liver transplantation or loco-regionary therapy
• Eligible for therapy with Atezolizumab / Bevacizumab according to standard of care
• Measurable disease per RECIST 1.1
• Preserved liver function with a Child-Pugh score A or B (maximally 7 points)
• Performance status ECOG 0-1