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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HRYZ-T102 Injection | Experimental | Patients will undergo lymphocytapheresis, then treatment with HRYZ-T102 TCR-T cells. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AFP Specific T Cell Receptor T Cells | Biological | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse events and serious adverse events | Incidence of adverse events and serious adverse events | 2 years |
| DLT | Dose-limiting toxicity | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate(ORR) | The percentage of subjects with PR or CR assessed by RECIST 1.1. | 2 years |
| Disease Control Rate (DCR) | The percentage of subjects with a confirmed CR, PR, or stable disease (SD) assessed by RECIST 1.1. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with positive anti-drug antibodies (ADA) | Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays | 2 years |
| Number of subjects with replication competent lentivirus (RCL) |
Inclusion Criteria:
The patient must be willing to sign the informed consent form.
Age ≥18 years and ≤75 years.
HLA-A 02:03 allele positive
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.
Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained AFP positive or serum AFP ≥400ng/ml.
Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
ECOG performance status ≤1.
Estimated life expectancy ≥4 months.
Patients must have at least one measurable lesion defined by RECIST 1.1.
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%.
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wenjin Huang | Contact | 021-61049928 | huangwenjin@shhryz.com |
| Name | Affiliation | Role |
|---|---|---|
| Xiaowu Huang, Doctor | Study Principal Investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhongshan Hospital Affiliated to Fudan University | Recruiting | Shanghai | Shanghai Municipality | China |
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| ID | Term |
|---|---|
| D006528 | Carcinoma, Hepatocellular |
| ID | Term |
|---|---|
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
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| 2 years |
| Duration of response (DoR) | Subjects who show a confirmed CR or PR as assessed by RECIST 1.1. | 2 years |
| Time to response (TTR) | Time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by RECIST 1.1. | 2 years |
| Progression-Free Survival(PFS) | The length of time from enrollment until the time of progression of disease | 2 years |
| Overall Survival (OS) | The interval of time between the date of T-cell infusion and the date of death. | 2 years |
| Duration of TCR T cells in-vivo persistence | Blood samples were collected to measure persistence of infused HRYZ-T102 | 2 years |
| Concentration of Cytokines (IL-2、IL-6、IL-10、TNFα、IFNγ) | 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. | 2 years |
RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
| 2 years |
| T cell subgroup in peripheral blood | Collect blood samples and analyze for T cell subgroup by flow cytometry at specified intervals before and after treatment with HRYZ-T102. | 2 years |
| D009369 | Neoplasms |
| D008113 | Liver Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D004066 | Digestive System Diseases |
| D008107 | Liver Diseases |