Using CAR-T cell therapy to treat advanced liver cancer

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

This study is testing a new type of immune therapy called CAR-T cell therapy to see if it can help people with advanced liver cancer who haven't had success with other treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd. (industry)
• Drugs / interventions: CAR-T
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06144385 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of a novel immunotherapy, specifically CAR-GPC3 T cells, in patients with advanced hepatocellular carcinoma who have not responded to previous treatments. It is a single-arm, open-label, dose-escalation study, meaning all participants will receive the treatment without a control group for comparison. The study aims to determine the appropriate dosage and monitor the patients for any adverse effects or improvements in their condition. Participants will be closely monitored for their response to the therapy over the course of the trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with histologically-confirmed advanced hepatocellular carcinoma that has progressed after prior treatments.

Not a fit: Patients with active hepatitis B infections or those who are not expected to benefit from any local therapies will not receive 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: While CAR-T cell therapies have shown promise in other cancers, this specific approach for hepatocellular carcinoma is novel and has not been extensively tested in prior studies.

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

Where this trial is running

Wuhan, Hubei

• Tao Zhang — Wuhan, Hubei, China (RECRUITING)

Study contacts

• Principal investigator: Tao Zhang, MD, PhD — Wuhan Union Hospital, China
• Study coordinator: Tao Zhang, MD, PhD

Conditions: Liver Carcinoma, Hepatic Cell Carcinoma