This prospective, single-center, single-arm phase 2 study evaluates the efficacy and safety of adding oral fecal microbiota transplantation (FMT) capsules to continued immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) therapy in adults with advanced hepatocellular carcinoma (HCC) whose disease has progressed during ICI-TKI therapy.
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;
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;
Single group
Oral fecal microbiota transplantation capsules
Biological/VaccineOral fecal microbiota transplantation capsules (300 mg per capsule) are administered at a dose of 6 capsules per day for 10 consecutive days in each 21-day cycle, for a total of 4 cycles. Participants continue their pre-enrollment ICI-TKI regimen during FMT treatment.
Progression-Free Survival (PFS)
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.
Overall Survival (OS)
Time from the first dose of FMT capsules to death from any cause.
Objective Response Rate (ORR)
Proportion of participants with a best overall response of complete response or partial response according to RECIST version 1.1.
Duration of Response (DOR)
For participants with a complete or partial response, time from the first documented response to radiographic disease progression or death from any cause, whichever occurs first.
Disease Control Rate (DCR)
Proportion of participants with a best overall response of complete response, partial response, or stable disease according to RECIST version 1.1.
Gut microbiome diversity by shotgun metagenomic sequencing
Longitudinal fecal samples will be analyzed by shotgun metagenomic sequencing to assess alpha diversity, beta diversity, and changes in overall gut microbial community structure.
Gut microbiome taxonomic and functional profiling by shotgun metagenomic sequencing
Longitudinal fecal samples will be analyzed by shotgun metagenomic sequencing to characterize microbial taxonomic composition and functional pathways, and to evaluate treatment-associated changes over time.
Single-cell transcriptomics
Single-cell RNA sequencing will be used to characterize cell populations, cellular states, and treatment-associated transcriptional changes.
Plasma metabolomics
Longitudinal plasma samples will be analyzed by mass spectrometry-based metabolomic profiling to identify treatment-associated changes in metabolites and metabolic pathways.
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Xu Yong, MD
Lead sponsor
Shenzhen Third People's Hospital
Sponsor institution
Nanjing Xiershou Biotechnology Co., Ltd
Collaborator
