CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. The patient must be willing to sign the informed consent form.
2. Age ≥18 years and ≤75 years.
3. HLA-A 02:03 allele positive
4. Histologically-confirmed AFP positive hepatocellular carcinoma (HCC) or other solid tumor, No benefits from curative surgery or other local therapies are expected ,at least one prior line of systematic treatment at screening, judged by investigators.
5. Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained AFP positive or serum AFP ≥400ng/ml.
6. Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
7. ECOG performance status ≤1.
8. Estimated life expectancy ≥4 months.
9. Patients must have at least one measurable lesion defined by RECIST 1.1.
10. Patients with any organ dysfunction as defined below:

    Leukocytes≥3.0 x 10\^9/L; blood platelets ≥75 x 10\^9/L; hemoglobin≥85g/L; Absolute lymphocyte count≥0.8 x 10\^9/L Serum albumin ≥ 30g/L; total bilirubin≤3×ULN; ALT/AST≤3×ULN ; Creatinine clearance ≥50mL/min; or serum creatinine ≤1.5×ULN; INR≤1.5×ULN; APTT≤1.5×ULN; LVEF≥50%; SpO2≥92%.
11. Subjects with potential fertility must agree to use effective contraceptive methods during the whole trials period and at least 1 year after receiving HRYZ-T102 cell transfusion treatment. HCG test for female with potential fertility must be negative within 7 days before apheresis.

Exclusion Criteria:

1. Toxicity of previous treatment has not been mitigated or ≤ Grade 1 at screening.
2. Another primary malignancy within 5 years (with some exceptions for completely-resected early-stage tumors)
3. With severe cardiovascular disease or presence of clinically-relevant central nervous system (CNS) disorders in six months before screening.
4. Systematic autoimmune disorders requiring long-term systematic immunosuppression
5. Have a history of hypersensitivity to cyclophosphamide or fludarabine, and it is known that any ingredient used in the treatment of this study will produce allergic reactions.
6. Current presence of or previously with hepatic encephalopathy
7. Organ transplanters and allogeneic cell transplanters.
8. Have a history of gastrointestinal bleeding or a definite tendency to gastrointestinal bleeding within 3 months before screening
9. Hereditary or acquired bleeding (e.g. coagulation dysfunction) or a tendency to clot
10. Subject has active infection or unexplained fever during screening and prior to cell transfusion
11. Have central nervous system metastasis with symptoms
12. Known HIV or syphilis infection, and/or active hepatitis C virus infection.
13. HBV infect subjects with HBV-DNA≥2000IU/ml
14. Pregnant or lactating female, or those whose HCG test is positive before enrollment.
15. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure

主要终点：Adverse events and serious adverse events · Incidence of adverse events and serious adverse events · 2 years；DLT · Dose-limiting toxicity · 2 years
次要终点：Objective Response Rate（ORR）；Disease Control Rate (DCR)；Duration of response (DoR)；Time to response (TTR)；Progression-Free Survival（PFS）；Overall Survival (OS)；Duration of TCR T cells in-vivo persistence；Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ)

• HRYZ-T102 Injection · EXPERIMENTAL · Patients will undergo lymphocytapheresis, then treatment with HRYZ-T102 TCR-T cells.

This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of HRYZ-T102 TCR-T Cell in patients with AFP positive advanced hepatocellular carcinoma and other solid tumors refractory to prior systematic treatments.