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

Phase 1

Recruiting

• Conditions: Hepatic Cell Carcinoma
• Interventions: Biological: AFP Specific T Cell Receptor T Cells

• Registration Number: NCT06515314
• Lead Sponsor: HRYZ Biotech Co.

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.

Study Timeline

• Status Verified: 2024-07
• Study First Submitted: 2024-07-17
• Study First Submitted QC: 2024-07-17
• Last Update Submitted: 2024-07-17
• Study First Posted: 2024-07-23
• Last Update Posted: 2024-07-23
• Study Start: 2024-08-10
• Primary Completion: 2026-08-10
• Study Completion: 2027-08-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HRYZ-T102 Injection	AFP Specific T Cell Receptor T Cells	Patients will undergo lymphocytapheresis, then treatment with HRYZ-T102 TCR-T cells.

Primary Outcome Measures

Name	Time	Method
Adverse events and serious adverse events	2 years	Incidence of adverse events and serious adverse events
DLT	2 years	Dose-limiting toxicity

Secondary Outcome Measures

Name	Time	Method
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.
Objective Response Rate（ORR）	2 years	The percentage of subjects with PR or CR 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.
Overall Survival (OS)	2 years	The interval of time between the date of T-cell infusion and the date of death.
Disease Control Rate (DCR)	2 years	The percentage of subjects with a confirmed CR, PR, or stable disease (SD) 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.
Progression-Free Survival（PFS）	2 years	The length of time from enrollment until the time of progression of disease
Duration of TCR T cells in-vivo persistence	2 years	Blood samples were collected to measure persistence of infused HRYZ-T102

Trial Locations

Locations (1)

Zhongshan Hospital Affiliated to Fudan University; 🇨🇳 Shanghai, Shanghai, China