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

Prior treatment

• 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;
• 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；
• Received abdominal radiotherapy or administered radioactive substances within 28 days prior to PD-1 monoclonal antibody re-challenge;
• History of gastrointestinal perforation and/or fistula within 6 months prior to PD-1 monoclonal antibody re-challenge;
• Active gastrointestinal bleeding within 1 week before the first fecal microbiota transplantation.
• Occurrence of infection within 28 days prior to PD-1 monoclonal antibody re-challenge;
• Received live or attenuated vaccines within 30 days prior to PD-1 monoclonal antibody re-challenge, or planned vaccination during the study period;
• 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;

Other illness

• 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);
• Known history of primary immunodeficiency or HIV infection;
• Known history of active tuberculosis (TB)；
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Suffering from active, known or suspected autoimmune disease, or with a history of autoimmune disease;
• History of cardiovascular or cerebrovascular events or accidents within 6 months;
• Other conditions deemed by the investigator to be inappropriate for enrollment, including patients with hyperprogressive disease.

• Clinically or pathologically confirmed unresectable primary hepatocellular carcinoma;
• Liver cancer patients with BCLC stage B or C;
• Not receiving systematic treatment before enrollment;
• Patients with acquired resistance who achieved disease control (DCR: CR, PR, or SD) following first-line targeted-immunotherapy but later experienced disease progression (PD);
• Child Pugh score ≤ 7 points;
• Subject must have at least 1 measurable target lesion examined by CT or MRI according to RECIST1.1 criteria;
• The Eastern Oncology Consortium (ECOG) Behavioral status score was 0 or 1.