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

NCT ID: NCT05926726

Last Updated: 2023-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-01-01
• Study Completion Date: 2026-12-31

Brief 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.

Conditions

Hepatocellular Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CAR-GPC3 T cells

The safety and efficacy of JWATM214 will be evaluated in a 'BOIN'-designed dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10\^8, 3×10\^8, and 10×10\^8, whereas the dosage 0.5×10\^8 and 30×10\^8 CAR-T cells will be selected as optional back-up doses for potential escalation or de-escalation.

Group Type: EXPERIMENTAL

CAR-GPC3 T cells

Intervention Type: BIOLOGICAL

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.

Interventions

CAR-GPC3 T cells

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.

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qiang Xia, Prof. MD

Role: STUDY_CHAIR

Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

Hao Feng, MD.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

Locations

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Hao Feng, MD.,Ph.D

Role: CONTACT

surgeonfeng@live.com

008615000901110

Facility Contacts

Hao Feng, MD, PhD

Role: primary

surgeonfeng@live.com

Other Identifiers

JWATM214001

Identifier Type: -

Identifier Source: org_study_id