Oral Fecal Microbiota Transplantation in Advanced Hepatocellular Carcinoma After Progression on ICI-TKI Therapy

This is a prospective, single-center, single-arm clinical study evaluating the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules in patients with advanced hepatocellular carcinoma (HCC) whose disease has progressed during immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) therapy.

After enrollment, participants will continue the same ICI-TKI regimen according to its prescribed schedule. In addition, oral FMT capsules (300 mg per capsule) will be administered at 6 capsules per day for 10 consecutive days in each 21-day cycle, for a total of 4 cycles. ICI-TKI therapy will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion.

The primary endpoint is progression-free survival (PFS), defined as the time from the first dose of FMT capsules to the first documented radiographic disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.

Secondary endpoints include overall survival (OS), defined as the time from the first dose of FMT capsules to death from any cause; objective response rate (ORR), defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) according to RECIST version 1.1; duration of response (DOR), defined for participants with CR or PR as the time from the first documented response to radiographic disease progression or death from any cause, whichever occurs first; and disease control rate (DCR), defined as the proportion of participants with CR, PR, or stable disease (SD) according to RECIST version 1.1.

Adverse events will be evaluated and graded according to CTCAE version 5.0. Other assessments include protocol-specified imaging, laboratory tests, and quality-of-life measures.

Inclusion criteria

• Age 18-75 years old, gender is not limited;
• Confirmed imaging or histological diagnosis of unresectable HCC, BCLC stadium B or C;
• Clinical diagnosis of HCC progression during TKIs combined with ICIs treatment;
• Not suitable for local ablation or chemoembolization;
• Child-Pugh class A or B, with a score of ≤7;
• ≥ 1 measurable lesion (RECIST v1.1)
• ECOG PS 0-2

Exclusion criteria

• Use of antibiotics within 4 weeks prior enrollment;
• Diagnosis of immunodeficiency (e.g. HIV, immunosuppressants)
• Patients with known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation;
• Female patients who are pregnant or breastfeeding;
• Patients with untreated acute or chronic active hepatitis B or hepatitis C infection.
• Patients are currently undergoing clinical trials of other drugs;
• Patients are considered by the investigator to be unsuitable for inclusion.