A Phase 2 interventional study of Tislelizumab Combined With TKI and Fecal Microbiota Transplantation in Hepatocellular Carcinoma (HCC), sponsored by Wang Xin. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-09-02.
Sponsored by Wang Xin · Phase 2, Interventional, and Treatment
This is an open-label, multicenter, randomized controlled Phase II trial. Patients with advanced hepatocellular carcinoma (HCC) who developed secondary resistance to first-line targeted-immunotherapy were randomly assigned to receive either the original first-line targeted-immunotherapy combined with FMT and PULSAR (experimental group), or second-line targeted-immunotherapy (control group). The first-line targeted-immunotherapy regimens consisted of tislelizumab combined with one of the first-line evidence-based tyrosine kinase inhibitors (TKIs), including lenvatinib, donafenib, apatinib, and sorafenib. Given that this study enrolled patients who progressed after an initial response to first-line targeted-immunotherapy, the second-line regimen in the control group continued tislelizumab immunotherapy while switching the TKI to regorafenib, an agent with second-line evidence.
Based on previous studies, the investigators aim to further explore the difference in efficacy between continuing the original targeted-immunotherapy regimen combined with FMT and PULSAR, versus standard second-line therapy, in patients with acquired resistance who experienced disease progression (PD) after achieving disease control (CR, PR or SD) with first-line targeted-immunotherapy.
The investigators will investigate whether fecal microbiota transplantation reshapes the tumor immune microenvironment by altering gut microbiota composition, and whether it can enhance immunogenicity and reverse the efficacy of immunotherapy plus TKI treatment when combined with radiotherapy. The investigators will also explore the immune-activating effect and synergistic mechanism of the PULSAR radiotherapy modality.
Primary Objective: Progression-Free Survival (PFS); Secondary Objectives: Overall Survival (OS), Objective Response Rate (ORR), Disease Control Rate (DCR), incidence and severity of Adverse Events (AE), changes in gut microbiota indices, and changes in tumor immune microenvironment indices.
3,182 studies on the registry are indexed under Carcinoma, Hepatocellular; 954 are open to participants now.
This study's planned enrollment of 64 is above the median of 55 across 2,298 interventional studies indexed under Carcinoma, Hepatocellular.
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Key Inclusion Criteria:
Key Exclusion Criteria:
The experimental group patients will receive PULSAR combined with FMT and the original first-line target immunotherapy regimen (Tislelizumab+TKI) as second-line treatment until disease progression, death, or intolerable toxicity occurs.
Drug: Tislelizumab Combined With TKI · Drug: Fecal Microbiota Transplantation · Radiation: PULSAR
The control group patients will receive second-line treatment with Tislelizumab combined with regorafenib until disease progression, death, or intolerable toxicity occurs.
Drug: Tislelizumab Combined With TKI
Tislelizumab: 200mg, intravenous infusion, once every 3 weeks, D1. Targeted therapy (TKI): first-line treatment options such as lenvatinib, donafenib, apatinib, sorafenib, etc. The second-line control group was treated with Regorafenib 80mg once a day, taken for three weeks and rested for one week. Combination therapy is administered every 21 days as a cycle until disease progression, death, or intolerable toxicity occurs.
Fecal Microbiota Transplantation (FMT): 30g, orally administered, once every 3 weeks, D-3 (3 days before systemic treatment). After the preparation of the microbiota solution or capsule, store it in a -80 ℃ refrigerator. Transfer the microbiota solution or capsule to room temperature and seal it 15 minutes before use. Fasting is required 4 hours before microbiota transplantation and 1 hour after transplantation.
PULSAR : Choose 3-5 lesions, but cannot include all newly progressing lesions (new progressing lesions must not be treated with radiotherapy to observe efficacy), once a month for 8Gy, for a total of 3-5 times.
Also known as: Personalized Ultra-fractionated Stereotactic Adaptive Radiotherapy
Progression-free survival (PFS)
PFS is defined as the time from the date of randomization until the date of disease progression according to RECIST 1.1 or death by any cause.
Time frame: From randomization to the first occurrence of disease progression or death from any cause up to approximately 24 months
Overall Survival (OS)
OS is defined as the time from the date of randomization until death due to any cause.
Time frame: From randomization to death due to any cause up to approximately 24 months
Objective Response Rate (ORR)
ORR (per RECIST 1.1 as assessed by the Investigator) was defined as the number (%) of participants with at least 1 confirmed visit response of CR or PR until progression, or the last evaluable assessment in the absence of progression.
Time frame: From date of randomization until the date of first documented progression, assessed up to 24 months
Disease Control Rate (DCR)
Number (%) of participants with CR, PR, or SD.
Time frame: From date of randomization until the date of first documented progression, assessed up to 24 months
Number of participants with adverse events (AEs)
Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0, vital signs, and clinical laboratory test results in the Safety Analysis Set
Time frame: Up to 24 months
Changes in gut microbiota indicators
Changes in patient microbiome will be determined by analysis of gut bacterial composition in patient stool samples at baseline and post-FMT.
Time frame: At baseline (prior to FMT), first efficacy evaluation (approximately 9 weeks post-FMT), and exit from the group
Changes in tumor immune microenvironment indicators
Effects on the patient immune microenvironment will be assessed by examining changes in peripheral blood immune cells （including CD3, CD4, CD8 T cells, B cells, macrophages, NK cells, Th1, Th2, Th17, and Treg cells）at baseline and post-FMT.
Time frame: At baseline (prior to FMT), first efficacy evaluation (approximately 9 weeks post-FMT), and exit from the group
Plan to share: Undecided
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