Clinical Study on the Safety and Efficacy of QY-1-T in the Treatment of HBV-associated Advanced Liver Cancer
The vast majority of liver cancers have an insidious onset and are often asymptomatic in the early stages, making early diagnosis difficult. Once diagnosed, most liver cancers have reached locally advanced stages or distant metastases, equivalent to Barcelona stage (BCLC) C-D. The tumors progress rapidly and there is a lack of effective treatments. The survival period of cancer patients is generally only 3-6 months. Cellular immunotherapy, including CAR-T and TCR-T, is considered a new hope for the treatment of cancer. The purpose of this study is to explore the safety of QY-1-T (a TCR-T targeting HBV) in the treatment of HBV-related liver cancer, and to preliminarily evaluate the efficacy of QY-1-T in patients with HBV-related advanced liver cancer.
• Subjects aged 18-75 years old (male or female)
• The subject voluntarily participate and have the ability to sign the informed consent independently
• Patient with advanced hepatocellular carcinoma (HCC) confirmed by histopathology or cytology (BCLC stage B and C, or CNLC stage IIA/IIB and IIIA/IIIB). One of the following four conditions applies:a. Patients with advanced hepatocellular carcinoma (HCC) who are not candidates for surgery or local therapy and have previously failed or become intolerable after at least second-line or higher standardized systemic therapy (including but not limited to targeted therapy, immunotherapy, or chemotherapy) and whose disease progression or intolerance has been determined by imaging examination during or after treatment, Or patients whom the investigator believes could benefit. b. HCC patients with clinically confirmed recurrence or progression after local treatment, and the interval between treatment and enrollment is at least 4 weeks. c. HCC recurrence after resection progresses or is not tolerated by systemic therapy or TACE/HAIC or radiofrequency ablation, and the interval between treatment and entrainment is at least 4 weeks. d. Recurrence of liver cancer after liver transplantation progresses or is not tolerated after systemic therapy or TACE/HAIC or radiofrequency ablation, and the interval between treatment and entrainment is at least 4 weeks
• Prior systemic therapy should be discontinued for at least 2 weeks prior to enrollment
• The expected survival time is more than 6 months
• The subject has at least one tumor lesion that can be measured according to RECIST1.1
• Hepatitis B virus surface antigen (HBsAg) positive or previous positive history
• The HLA typing of peripheral blood was HLA-A\*11:01
• Non-cirrhosis or compensatory cirrhosis Child-Pugh \< 7 score
⁃ ECOG scoring standard ≤1
⁃ Blood routine and blood biochemical indicators: a. white blood cells ≥3×10\^9/L. b. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× upper limit of normal (ULN). c. Serum total bilirubin ≤2×ULN. d.eGFR≥60ml /min. e. Hemoglobin \> 90g/L. f. Platelet count ≥50×10\^9/L. g. Creatinine ≤1.5×ULN. h. International standardized ratio INR≤1.5 or activated partial thrombin time (APTT) extended within 10s.
⁃ Female subjects of childbearing age, whose serum pregnancy tests must be negative, and all subjects must agree to take effective contraceptive measures during the test
⁃ Subject agrees to abstain from alcohol during the study
⁃ The subject is willing and able to follow all treatment procedures and protocols