Hepatic Cell Carcinoma
Conditions
Brief summary
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.
Detailed description
This study plans to enroll 12-24 patients to assess the safety of HRYZ-T102. Subjects who meet the eligibility criteria will receive a single dose of HRYZ-T102 injection .The patient will be followed up 24 months.
Interventions
BIOLOGICALAFP Specific T Cell Receptor T Cells
AFP Specific T Cell Receptor T Cells On day 1, the TCR-T cells will be administered intravenously. Drug: Fludarabine + Cyclophosphamide Fludarabine: 25mg/m²/day×3days; Cyclophosphamide: 250mg/m²/day×3 days
Sponsors
Shanghai Ruiliyuan Biotechnology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events and serious adverse events | 2 years | Incidence of adverse events and serious adverse events |
| DLT | 2 years | Dose-limiting toxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | 2 years | The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1. |
| Duration of response (DoR) | 2 years | Subjects who show a confirmed CR or PR as assessed by RECIST 1.1. |
| Time to response (TTR) | 2 years | Time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by RECIST 1.1. |
| Objective Response Rate（ORR） | 2 years | The percentage of subjects with PR or CR assessed by RECIST 1.1. |
| Overall Survival (OS) | 2 years | The interval of time between the date of T-cell infusion and the date of death. |
| Duration of TCR T cells in-vivo persistence | 2 years | Blood samples were collected to measure persistence of infused HRYZ-T102 |
| Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) | 2 years | Collect blood samples and analyze for presence of cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) at specified intervals before and after treatment with HRYZ-T102. |
| Progression-Free Survival（PFS） | 2 years | The length of time from enrollment until the time of progression of disease |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects with positive anti-drug antibodies (ADA) | 2 years | Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays |
| T cell subgroup in peripheral blood | 2 years | Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T102. |
| Number of subjects with replication competent lentivirus (RCL) | 2 years | RCL exposure will be assessed by polymerase chain reaction (PCR) based assay. |
Countries
China
Contacts
Primary ContactWenjin Huang
Outcome results
None listed