HRYZ-T102 TCR-T Cell for AFP Positive Advanced HCC and Other Solid Tumors

A Phase 1, Single-arm, Open-label, Dose-escalation Study of AFP Specific T Cell Receptor Transduced T Cells Injection（HRYZ-T102）in Patients With AFP Positive Advanced Hepatocellular Carcinoma and Other Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatic Cell Carcinoma
• Intervention / Treatment: Biological: AFP Specific T Cell Receptor T Cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenjin Huang; Phone Number: 021-61049928; Email: huangwenjin@shhryz.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Zhongshan Hospital Affiliated to Fudan University
      • Contact: Xiaowu Huang, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HRYZ-T102 Injection; Patients will undergo lymphocytapheresis, then treatment with HRYZ-T102 TCR-T cells.	Biological: AFP 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	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
Overall Survival (OS)	The interval of time between the date of T-cell infusion and the date of death.	2 years
Progression-Free Survival（PFS）	The length of time from enrollment until the time of progression of disease	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with replication competent lentivirus (RCL)	RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.	2 years
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
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

Collaborators and Investigators

• Sponsor: Shanghai Ruiliyuan Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Xiaowu Huang, Doctor, Study Principal Investigator

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2024
• Primary Completion (Estimated): August 10, 2026
• Study Completion (Estimated): August 10, 2027

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 23, 2024

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 24, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: H-T02-C1001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No