A Phase 1 Study of BST02 in Treating Locally Advanced Liver Cancer

Who cannot join

• Pregnant or lactating women;
• Subjects with a prior history of severe allergy and hypersensitivity to the investigational drugs including, but not limited to, cyclophosphamide, fludarabine, IL-2, and the components of BST02;
• Subjects with prior or current history of hepatic encephalopathy; patients with known central nervous system metastases uncontrolled by other treatment or untreated; with exception of patients who have stabilized their symptoms after treatment, and discontinued the treatment of glucocorticoid and anticonvulsant medications ≥4 weeks prior to lymphodepletion preconditioning;
• Presence of clinically significant ascites, defined as: Positive signs of ascites on physical examination or ascites that needs to be controlled with interventional therapy (only those with ascites on imaging without intervention may be included); (5) The Indocyanine Green retention test after 15 min (ICG-R15) is ≥30%;
• History of organ transplantation, hematopoietic stem cell transplantation; (7) Other serious medical conditions that may limit the subject's participation in this trial, including but not limited to: Hypertension that is uncontrolled by medication (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at rest after taking medication); Uncontrolled diabetes: Fasting blood glucose levels remain above 1 mmol/L after standardized treatment with insulin; Unstable cardiovascular diseases: Uncontrolled congestive cardiac failure, infarct myocardial or unstable arrhythmia or unstable arrhythmia within the last 6 months, percutaneous coronary interventional procedure, acute coronary syndromes, coronary artery bypass transplant; cerebrovascular accident, transient ischemic attack, cerebral embolism, deep vein thrombosis, etc.; Uncontrolled respiratory system disorder: Pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, etc.; Active, autoimmune diseases requiring systemic therapy during the period of the study: Subjects with eczema, vitiligo, psoriasis, alopecia, or Graves's disease who do not require systemic treatment within the last 2 years, other autoimmune disorders that are not expected to recur, and subjects with type I diabetes mellitus who require only insulin replacement therapy may be enrolled; Active infection or active tuberculosis infection with a need for systemic therapy; Mental illness, except for mild depression, and other mild conditions; (8) Patients who are HIV-positive, or positive for syphilis spirochete antibodies; Patients with active hepatitis B or C are required to adopt antiviral therapy during the whole study. Active hepatitis B is defined as positive hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) and HBV-DNA >2000 IU/ml. Active hepatitis C is defined as HCV RNA above the lower limit of detection; (9) Subjects have taken any immunosuppressive drugs, such as corticosteroids, within 4 weeks prior to TIL sampling or had combined diseases needing application of immunosuppressive medications for the duration of the trial as judged by the investigator. However, physiologic doses of glucocorticoids (i.e., a maximum dose of 15 mg/day for prednisone or an equivalent dose of other glucocorticoids) are permitted, and inhalational, intranasal, topical, or prophylaxis use of corticosteroids are allowed against contrast allergy; (10) Subjects who have received anti-PD-1/ PD-L1 monoclonal antibody treatment within 4 weeks prior to lymphodepletion preconditioning , or undergone local treatments such as surgery (except BST02 sampling surgery), interventional therapy, radiotherapy, ablation, or systemic therapy against liver cancer (including those who participated in other clinical trials of drug therapy; metabolism of drugs with 5 half-lives of less than 4 weeks, whichever is shorter); or immunotherapy such as thymopeptide, interferon, or any traditional Chinese medicine used for tumor control within 1 week prior to lymphodepletion preconditioning ; (11) Subjects who have received a live vaccine within 3 months prior to screening or planned to receive a live vaccine during the trial; (12) Subjects who have undergone major surgery within 4 weeks prior to screening or planned to receive surgery during the trial period (except for TIL sampling surgery); (13) Patients with surgical complications or delayed wound healing prior to lymphodepletion preconditioning who, in the judgment of the investigator, will be at increased risk for lymphodepletion, TIL therapy, IL-2 adjuvant therapy, or infection; (14) Subjects who have diagnosed as combined other primary malignant neoplasm within 5 years prior to screening, excluding radically treated basal cell carcinoma of skin, squamous cell carcinoma of skin, and/or radically resected carcinoma in situ; (15) Subjects who have received cell therapy products 6 months prior to lymphodepletion preconditioning; (16) Subjects with known alcoholism, drug or substance abuse, and others who, in the opinion of the investigator, are not suitable for participation in this trial.