PULSAR Combined With Fecal Microbiota Transplantation for Advanced Hepatocellular Carcinoma Progressing After First-Line Targeted-Immunotherapy

Key Inclusion Criteria: 1. Clinically or pathologically confirmed unresectable primary hepatocellular carcinoma; 2. Liver cancer patients with BCLC stage B or C; 3. Not receiving systematic treatment before enrollment; 4. Patients with acquired resistance who achieved disease control (DCR: CR, PR, or SD) following first-line targeted-immunotherapy but later experienced disease progression (PD); 5. Child Pugh score ≤ 7 points; 6. Subject must have at least 1 measurable target lesion examined by CT or MRI according to RECIST1.1 criteria; 7. The Eastern Oncology Consortium (ECOG) Behavioral status score was 0 or 1. Key Exclusion Criteria: 1. Failure to recover to NCI-CTC AE Grade ≤1 (excluding alopecia and fatigue) or to baseline level from toxicities and/or complications of prior interventions before PD-1 monoclonal antibody re-challenge; 2. Subjects requiring systemic therapy with corticosteroids (\>10 mg prednisone equivalent daily) or other immunosuppressive agents within 14 days prior to PD-1 monoclonal antibody re-challenge； 3. Received abdominal radiotherapy or administered radioactive substances within 28 days prior to PD-1 monoclonal antibody re-challenge; 4. History of gastrointestinal perforation and/or fistula within 6 months prior to PD-1 monoclonal antibody re-challenge; 5. Active gastrointestinal bleeding within 1 week before the first fecal microbiota transplantation. 6. Occurrence of infection within 28 days prior to PD-1 monoclonal antibody re-challenge; 7. Active infection requiring systemic antimicrobial therapy before PD-1 monoclonal antibody re-challenge and intestinal microbiota transplantation, excluding local infections requiring only topical antibiotics (e.g., skin infections); 8. Received live or attenuated vaccines within 30 days prior to PD-1 monoclonal antibody re-challenge, or planned vaccination during the study period; 9. Known history of primary immunodeficiency or HIV infection; 10. Active or previously documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, chronic diarrhea), except patients with chronic diarrhea who had no recurrence within 2 years before enrollment; 11. Known history of active tuberculosis (TB)； 12. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; 13. Suffering from active, known or suspected autoimmune disease, or with a history of autoimmune disease; 14. History of cardiovascular or cerebrovascular events or accidents within 6 months; 15. Other conditions deemed by the investigator to be inappropriate for enrollment, including patients with hyperprogressive disease.