A Study to Evaluate Safety and Efficacy of Armored CAR-T Cell Injection C-CAR031 in Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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A study that aimed to assess the safety and anti-tumor activity of CCAR031 injection in unresectable HCC patients.

Detailed Description
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This study plans to enroll 4-20 patients to assess the safety of C-CAR031. Subjects who meet the eligibility criteria will receive a single dose of C-CAR031 injection, and will be followed up post treatment for safety monitoring. The follow up period will last 12 months.

Official Title
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A Clinical Study to Evaluate Safety and Efficacy of C-CAR031 Armored CAR-T Cell Injection in Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: TC-CAR031


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Voluntary participation and able to sign the informed consent form 2. Aged 18 to 70 years at screening 3. Patients with histologically confirmed hepatocellular carcinoma (HCC) who meet the following requirements: a. Barcelona Clinic Liver Cancer Stage B or C (BCLC B/C) b. Child-Pugh score ≤ 6 c. Positive cell membrane GPC3 expression in at least 35% of tumor cells 4. Patients with relapsed / progressive disease after at least one prior standard systemic therapies for HCC, or ineligible to accept/unable to tolerate the systemic therapies. Standard systemic therapies may include targeted drugs (such as Sorafenib, Lenvatinib, Donafenib, Apatinib), immune checkpoint inhibitors (such as Atezolizumab, Pembrolizumab, Camrelizumab, Sintilimab, Nivolumab, Toripalimab, Tislelizumab) or chemotherapeutic drugs (such as Oxaliplatin and 5-fu) 5. At least one measurable target lesion (as per RECIST v1.1) 6. WHO/ECOG performance status (PS) score of 0 or 1 point 7. Expected survival ≥ 12 weeks 8. Left ventricular ejection fraction (LVEF) by echocardiography ≥ 45% 9. No active infection in the lungs 10. Laboratory tests: a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L b. Lymphocyte count ≥ 0.4 × 109/L c. Platelet count ≥ 60 × 109/L d. Hemoglobin ≥ 80 g/L e. Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) f. AST and ALT ≤ 5 × ULN g. Serum creatinine ≤ 1.5 × ULN h. Prothrombin time (PT): prolonged PT ≤ 4 s 11. Patients without history of HBV infection, or with HBV DNA < 500 IU/mL (or 2500 copies/mL) at screening who agree to receive anti-virus therapies throughout the study according to the guidelines 12. Negative serum or urine pregnancy test results for females of child-bearing age at screening; In addition, they should agree to take effective contraceptive measures throughout the study 13. Patients who agree to abstain from drinking throughout the study Exclusion Criteria: 1. History of severe allergies or allergic to the excipient DMSO of the cell product 2. History of liver transplantation 3. History of prior cell therapy 4. Tumor volume > 70% of the liver 5. portal stem vein tumor thrombus 7. Metastases to bones or central nervous system (CNS), or involved CNS diseasesincluding hepatic encephalopathy, epilepsy, cerebrovascular accidents, etc. 8. Receipt of radiotherapy within 6 weeks prior to apheresis 9. Receipt of Local therapy (such as surgery, ablation, and intervention) within 4 weeks prior to apheresis or presence of unhealed wounds before apheresis 10. Receipt of systemic treatment and failure to meet the minimum requirements for wash-out periods before apheresis: a. Immune checkpoint inhibitors: 6 weeks b. Systemic anti-tumor therapies using experimental anticancer drugs or other Chinese herbal medicines and Chinese patent medicines with unclear mechanisms:2 weeks c. Steroids (except inhaled steroids) or other immunomodulators (including interleukins, interferons, and thymosins) of systemic therapeutic dose: 2 weeks 11. Other history of primary cancers, excluding:a. Nonmelanoma skin cancer cured by resection (such as basal cell carcinoma) b. Cured carcinoma in situ (such as cervical cancer, bladder cancer, and breast cancer) 12. Active hepatitis C virus infection (HCV RNA positive) 13. Syphilis infection 14. History of active/immunodeficient diseases (including but not limited to HIV, systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis, myasthenia gravis, Graves' disease, and hypophysitis; excluding: vitiligo or alopecia, hypothyroidism in patients with stable medical conditions after hormone replacement therapy, any chronic skin conditions that need no systemic treatment, and other diseases judged by the investigator to be of no clinical significance) 15. Persistent and active infections (excluding prophylactic anti-infectives) 16. Uncontrolled hypertension, diabetes, arrhythmia, and symptomatic congestive heart failure 17. Dementia or mental state changes supported by obvious clinical evidence 18. Cardiac insufficiency: class III or IV, according to the New York Heart Association (NYHA) functional classifications 19. Unstable heart or lung diseases 20. Obvious bleeding risks or tendencies 21. Females who are pregnant or breastfeeding or expect to be pregnant or breastfeeding during the study 22. Other diseases that may add further risks to the subject or interfere with the study results as judged by the investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C-CAR031<br>Autologous C-CAR031 administered by intravenous (IV) infusion | Biological: TC-CAR031<br>* Targeting GPC3 armored CART cell injection (C-CAR031)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TEAEs | treatment emergent adverse events | start pretreatment to 12 months | 
| AESIs | adverse events of special interest | start pretreatment to 12 months |