Clinical trial NCT06144385: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Liver Carcinoma
Hepatic Cell Carcinoma
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-11-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Rate of dose-limiting toxicities (DLTs)
timeFrame: 28 days
measure: Rate and severity of adverse events (AEs) and severe adverse events (SAEs)
timeFrame: 2 years
measure: Rate and severity of clinically-significant abnormalities in laboratory testings
timeFrame: 2 years
Secondary outcomes:
measure: Copy number of the vector transgene of JWATM204 in peripheral blood
timeFrame: 1 year
measure: Objective response rate (ORR)
timeFrame: 2 years
measure: Disease Control Rate (DCR)
timeFrame: 2 years
measure: Progression-free survival (PFS)
timeFrame: 2 years
measure: Overal survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tao Zhang
state: Hubei
Study officials:
affiliation: Wuhan Union Hospital, China
name: Tao Zhang, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: