Treatment for advanced liver cancer using TCR-T cells

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 study is testing a new treatment using HRYZ-T102 TCR-T cells to see if it can help people with advanced liver cancer and other solid tumors that haven't improved with other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Ruiliyuan Biotechnology Co., Ltd. (Industry-sponsored)
• Drugs / interventions: cyclophosphamide, fludarabine
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06515314 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of HRYZ-T102 TCR-T cells in patients with AFP positive advanced hepatocellular carcinoma and other solid tumors that have not responded to previous treatments. It is a single-arm, open-label, dose escalation study aiming to enroll 12-24 patients who will receive a single dose of the HRYZ-T102 injection. Participants will be monitored for 24 months to assess treatment outcomes and safety. The study focuses on patients with specific genetic markers and measurable lesions.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with AFP positive advanced hepatocellular carcinoma or other solid tumors who have experienced treatment failure with prior therapies.

Not a fit: Patients with early-stage liver cancer or those who have not undergone prior systemic treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced liver cancer who have limited treatment alternatives.

How similar studies have performed: Other studies using TCR-T cell therapies have shown promising results, indicating potential for success in this novel approach.

Eligibility criteria

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

Where this trial is running

Shanghai, Shanghai Municipality

• Zhongshan Hospital Affiliated to Fudan University — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Xiaowu Huang, Doctor — Study Principal Investigator
• Study coordinator: Wenjin Huang

Conditions Hepatic Cell Carcinoma