GPC3-directed CAR-T in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

Trial Title: GPC3-directed CAR-T in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

NCT ID: NCT05926726

Condition: Hepatocellular Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular

Study type: Interventional

Study phase: N/A

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: CAR-GPC3 T cells
Description: Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM214 . During JWATM214 production, subjects will receive a preconditioning chemotherapy regimen of cyclophosphamide and fludarabine to deplete the lymphocytes. After lymphodepletion, subjects will receive single-dose treatment with JWATM214 by intravenous (IV) injection.
Arm group label: CAR-GPC3 T cells

Summary: This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous armored GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. 18-75 years-old, male or female 2. Voluntarily willing to participate in the study and sign the written informed consent form 3. Life expectation ≥12 weeks 4. Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1 5. Histologically-confirmed hepatocellular carcinoma (HCC) 6. No benefits from curative surgery or other local therapies are expected at screening, judged by investigators 7. Radiologically-confirmed progression disease after at least one prior line of systematic treatment and limited benefits from current guideline or consensus for hepatocellular carcinoma are expected at screening, judged by investigators 8. Fresh samples or FFPE, immunohistochemistry (IHC)-stained GPC-3 positive with intensity ++ or +++ 9. Per RECIST v1.1, at least one measurable lesion 10. Manageable lung metastasis 11. Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7 12. No active HBV infections 13. Adequate organ functions 14. Adequate venous access for APH 15. Non-hematological AEs induced by previous treatment must have recovered to CTCAE ≤1, except for alopecia and peripheral neuropathy 16. Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1year post infusion, and sperm donation is prohibited during the study 17. Women of childbearing potential must have negative serum β-hCG test result at screening and 48 hours prior to lymphodepletion Exclusion Criteria: 1. Cholangiocarcinoma or histological-mixed hepatocellular cholangiocarcinoma 2. Active brain metastasis 3. Primary lesion or infused lesions with the longest diameter ≥15cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator 4. Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors) 5. Systematic autoimmune disorders requiring long-term systematic immunosuppression 6. Previously treated with any genetically engineered modified T cell therapy (TCR-T/CAR-T) or other CGT 7. Active HCV, HIV, or syphilis 8. History of organ transplant 9. Uncontrolled or active infection at screening, prior to APH, 72 hours prior to lymphodepletion or 5 days prior to JWATM214 infusion 10. With severe cardiovascular disease 11. History or presence of clinically-relevant CNS disorders 12. Current presence of hepatic encephalopathy 13. ≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants 14. Active digestive ulcer or gastrointestinal bleeding within 3 months prior to screening 15. Pregnant or lactating women 16. Not satisfying wash-out period for APH 17. Unable or unwilling to comply with the study protocol, judged by the investigator 18. Other situations implying that the subject might not be appropriate to participate in the study 19. Previously allergic or intolerable to JWATM214 or its components

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Address:
City: Shanghai
Zip: 200127
Country: China

Status: Recruiting

Contact:
Last name: Hao Feng, MD, PhD
Email: surgeonfeng@live.com

Start date: January 1, 2023

Completion date: December 31, 2026

Lead sponsor:
Agency: RenJi Hospital
Agency class: Other

Source: RenJi Hospital

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05926726