Advance hepatocellular carcinoma
Conditions
Interventions
Trial group:YB1-X7 injection intravenous infusion, dose 2.75×10^7 cfu/person, every 4 weeks as a cycle, administered on D1, D8, D15, D22 of each cycle
Trial group:YB1-X7 injection intravenous infusion, dose 5.5×10^7 cfu/person, every 4 weeks as a cycle, administered on D1, D8, D15, D22 of each cycle
Trial group:YB1-X7 injection intravenous infusion, dose 1.1×10^8 cfu/person, every 4 weeks as a cycle, administered on D1, D8, D15, D22 of each cycle
Trial group:YB1-X7 injection intravenous infusion, dose 2.2×10^8 cfu/person, every 4 weeks as a cycle, administered on D1, D8, D15, D22 of each cycle
Trial group:YB1-X7 injection intravenous infusion, based on the recommended phase 2 dose (RP2D) determined in phase 1, every 4 weeks as a cycle, administered on D1, D8, D15, D22 of each cycle
Sponsors
Shanghai General Hospital
Eligibility
Sex/Gender
All
Age
20 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Patients voluntarily participate in the study, sign the Informed Consent Form (ICF), and are able to comply with the protocol-specified visits and relevant procedures; 2. Male or non-pregnant female patients, aged 20 to 80 years; 3. Patients with histologically confirmed HCC according to the 2024 CSCO Guidelines for Diagnosis and Treatment of Primary Liver Cancer; 4. Patients with Barcelona Clinic Liver Cancer (BCLC) stage determined as unresectable Stage B or Stage C hepatocellular carcinoma, who have progressed on or are intolerant to first-line therapy; 5. Failure of at least one prior first-line systemic therapy, with prior use of PD-1/L1 inhibitors and/or Tyrosine Kinase Inhibitors (TKIs); 6. Liver function Child-Pugh score Grade A or B, or those who can be reduced to Child-Pugh A or B after treatment, and with no history of hepatic encephalopathy; 7. Good general status, with an ECOG score of 0-1 within 7 days prior to enrollment; 8. Expected survival period of no less than 12 weeks; 9. Presence of at least one measurable target lesion according to mRECIST; 10. Subjects must have accessible tumor tissue samples. This can be a compliant fresh tumor tissue sample or archival tissue within 2 years prior to signing the ICF. If tumor tissue has been previously obtained (surgical/biopsy samples), preference is given to submitting one formalin-fixed, paraffin-embedded (FFPE) tumor sample in a paraffin block, or approximately 10 un-stained, freshly cut, serial sections on adhesive slides. 11. Laboratory blood test results during the screening period, with no receipt of any hematopoietic growth factors within 14 days prior to the test: (1) Absolute Neutrophil Count (ANC) >= 1.5×10^9/L; (2) Platelets >= 90 × 10^9/L; (3) Hemoglobin >= 90g/L (correction by blood transfusion is allowed); (4) Total Bilirubin = 50 mL/min (standard Cockcroft-Gault formula) or Cr < 1.5 × ULN; (6) Prothrombin Time (PT) and Activated Partial Thromboplastin Time (aPTT) < 1.5 × ULN. 12. Negative HIV antibody test result at screening; 13. For patients with active Hepatitis B Virus (HBV) infection: HBV DNA < 500 IU/mL obtained within 28 days prior to the initiation of study treatment, and having received anti-HBV treatment (according to local standard of care, e.g., Entecavir) for at least 14 days prior to enrollment and willing to continue treatment during the study; 14. Women of Childbearing Potential (WOCBP) must have a negative pregnancy test (ß-HCG) before starting treatment. WOCBP and men (engaging in sexual relations with WOCBP) must agree to use effective contraception uninterruptedly during the treatment period and for 6 months after the administration of the last dose of treatment.
Exclusion criteria
Exclusion criteria: 1. Patients with implanted medical devices (e.g., cardiac pacemaker, artificial heart valve, metallic orthopedic prosthesis); 2. Active or uncontrolled infection during screening or prior to the first dose of study drug; or unexplained fever (body temperature > 38.5 °C); 3. Hypersensitivity or intolerance to antibiotics active against Salmonella; or concurrent infectious disease requiring ongoing antibiotic therapy; 4. Prior treatment with oncolytic microbial therapy. 5. Central nervous system metastasis, including brain metastasis and/or meningeal metastasis; 6. Prior bone marrow or organ transplantation (including but not limited to liver transplantation) or awaiting transplantation; 7. History of other malignancies or multiple synchronous primary malignancies; 8. Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA > 500 IU/mL (lower limit of detection: HBV DNA = 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first study drug infusion or during the study, except for inhaled or topical use; 14. Patients with known hypersensitivity to the investigational product or any of its excipients; subjects with atopic constitution or a history of severe hypersensitivity reactions; 15. Patients with active or prior autoimmune diseases with potential for relapse, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.; 16. Existing cardiac symptoms or poorly controlled cardiac conditions: (1) New York Heart Association (NYHA) functional class >= II; (2) Unstable angina pectoris; (3) Myocardial infarction within 1 year; (4) Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; (5) Uncontrolled hypertension or hypotension despite pharmacotherapy (as judged by the investigator); (6) Valvular heart disease, mitral valve prolapse, or aortic disease; (7) Severe myocardial disease. 17. History of pulmonary embolism or severe lower extremity deep vein thrombosis requiring interventional therapy (e.g., in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-Limiting Toxicity (DLT) Incidence Rate;Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D);Objective Response Rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS);Progression-Free Survival (PFS);Disease Control Rate (DCR);Duration of Response (DOR);Pharmacokinetic (PK) Parameters (Tmax, Cmax, AUC0-t, AUC0-8, Vd, Kel, T1/2, MRT, CL, Cmin,ss, Cmax,ss, Cav,ss, AUC0-t, DF);Bacterial Clearance (in whole blood, saliva, urine, feces);Cytokine Level Changes;Tumor Tissue Pathological Changes (necrosis, immune cell infiltration, etc.) and YB1-X7 Colonization Level; | — |
Countries
China
Contacts
Public ContactWang Kang
Shanghai General Hospital
Outcome results
None listed