A Phase 1, Single-arm, Open-label, Dose-escalation Study of JWATM204 as T Cell-targeted Immunotherapy in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma

NCT ID: NCT06144385

Last Updated: 2024-01-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-24
• Study Completion Date: 2024-12-31

Brief Summary

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

Conditions

Liver Carcinoma; Hepatic Cell 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 JWATM204 will be evaluated in a Bayesian Optimal Interval Design (BOIN) dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10\^8, 3×10\^8, 10×10\^8, and 30×10\^8 CAR-T cells will be explored.

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 JWATM204 . During JWATM204 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 JWATM204 by intravenous (IV) injection.

Interventions

CAR-GPC3 T cells

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM204 . During JWATM204 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 JWATM204 by intravenous (IV) injection.

Intervention Type: BIOLOGICAL

Other Intervention Names

JWCAR204

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 available options for hepatocellular carcinoma are expected at screening, judged by investigators

8. Fresh samples or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained GPC-3 positive

9. Per RECIST v1.1, at least one measurable lesion

10. Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7

11. No active infections of hepatitis B virus

12. Adequate organ functions

13. Adequate venous access for apheresis

14. Non-hematological AEs induced by previous treatment must have recovered to CTCAE ≤1, except for alopecia and peripheral neuropathy

15. 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

16. Women of childbearing potential must have negative serum β-human chorionic gonadotropin (β-hCG) test result at screening and 48 hours prior to lymphodepletion

Exclusion Criteria

1. Active brain metastasis

2. Primary lesion or infused lesions with the longest diameter ≥15 cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator

3. Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)

4. Systematic autoimmune disorders requiring long-term systematic immunosuppression

5. Previously treated with any genetically engineered modified T-cell therapy nor other cell-gene therapy

6. Active infections of hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis

7. Uncontrolled or active infection at screening, prior to apheresis, 72 hours prior to lymphodepletion or 5 days prior to JWATM204 infusion

8. With severe cardiovascular disease History or presence of clinically-relevant central nervous system (CNS) disorders

9. With clinically-significant CNS disorders

10. Current presence of or previously with hepatic encephalopathy

11. ≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants

12. Pregnant or lactating women

13. Not satisfying pre-defined wash-out period for apheresis

14. Received plasma exchange within 14 days prior to apheresis

15. Unable or unwilling to comply with the study protocol, judged by the investigator, or other situations implying that the subject might not be appropriate to participate in the study

16. Vaccinated with live vaccinations against infectious diseases within 8 weeks prior to JWATM204 infusion

17. Previously allergic or intolerable to JWATM204 or its components

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

Sponsors

Shanghai Ming Ju Biotechnology Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tao Zhang, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Locations

Tao Zhang

Wuhan, Hubei, China

Site Status: RECRUITING

Countries

China

Central Contacts

Tao Zhang, MD, PhD

Role: CONTACT

1277577866@qq.com

+86 027-85726375

Facility Contacts

Tao Zhang, MD, PhD

Role: primary

Other Identifiers

JWATM204001

Identifier Type: -

Identifier Source: org_study_id