To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307
Study Details
Study Description
Brief Summary
To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307, Autologous Glypican 3 (GPC3) Targeted Chimeric Antigen Receptor T cell therapy in Patients with GPC3 Positive Advanced Hepatocellular Carcinoma who Have Failed Standard Therapy
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Detailed Description
A Dose-escalation, Single-arm, Open-Label, Phase 1 Study
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: EU307 CAR-T Cell
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Biological: EU307 CAR-T Cell
Dose to be administered: a single dose
IV administration
Dosing rate: To be administrated at a rate of approximately 2 mL/min
|
Outcome Measures
Primary Outcome Measures
- AEs (including DLT) [up to 6 month from LPI]
In this study, DLT is defined as an AE related to the IP (EU307),and severity will be assessed according to NCI-CTCAE v5.0
- Production of replication competent lentiviruses (RCL) [up to 6 month from LPI]
- Development of anti-drug antibodies (ADA) [up to 6 month from LPI]
Secondary Outcome Measures
- ORR [up to 6 month]
Proportion of subjects with confirmed CR or partial response (PR) as best overall response (BOR)
- DoR [up to 6 month]
Time from confirmed tumor response (CR or PR) to confirmed progressive disease (PD)
- DCR [up to 6 month]
Proportion of subjects with confirmed CR, PR, or stable disease (SD) (≥ 6 weeks) as BOR
- TTR [up to 6 month]
Time from IP dosing to confirmed objective response (CR or PR)
- TTP [up to 6 month]
Time from IP dosing to PD
- PFS [up to 6 month]
Time from IP dosing to PD or all-cause death, whichever is earlier
- OS [up to 6 month]
Time from IP dosing to all-cause death
Other Outcome Measures
- Quantitative CAR-T DNA assay [up to 6 month]
- Immunological assessment [up to 6 month]
-To explore relationship to tumor response, parameters to be analyzed include, but are not limited to: IFN-g, TNF-a, IL-2, IL-6, IL-18, IL-10, RANTES, MCP-1, TGF--Analysis of T cells and immune cells
Eligibility Criteria
Criteria
Inclusion Criteria:
- To be eligible, subjects must meet all of the following criteria:
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Male or female adults ≥19 years old at the time of written informed consent
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Patients with histologically or cytologically diagnosed unresectable HCC refractory to first- or second-line standard therapy* with no other standard therapy available
- Including, but not limited to atezolizumab plus bevacizumab combination therapy and tyrosine kinase inhibitors (e.g., sorafenib, lenvatinib).
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Confirmed GPC3 positivity by IHC based on a liver tissue sample
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At least 1 measurable lesion based on mRECIST v1.1
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Child-Pugh score Class A or Class B(7)
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Life expectancy ≥3 months based on the judgment of the investigator
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ECOG PS 0 or 1
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Patients who have adequate bone marrow, liver, and kidney functions at the time of screening:
WBC ≥ 2,000 /μL ANC ≥ 1,000 /μL Platelet ≥ 80,000 /μL Hemoglobin ≥ 9.0 g/dL Albumin ≥ 2.8 g/dL AST and/or ALT ≤ 5ⅹULN Total bilirubin ≤ 2 x ULN Serum creatinine ≤1.5 x ULN, Creatinine clearance (CrCl) ≥ 30 mL/min PT(INR) ≤1.5 x ULN
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Negative serum pregnancy test in women of childbearing potential
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Women of childbearing potential or men who do not plan a pregnancy during the study period and who agree to use clinically adequate methods of contraception as follows:
- Hormone contraceptives (subcutaneous implants, injections, oral contraceptives, etc.), intrauterine device (IUD) (or intra uterine system [IUS]), subject's or partner's surgical sterilization (vasectomy, tubal ligation, etc.), double barrier methods (combined use of barrier methods such as combined use of cervical cap or diaphragm plus male condom)
- Written informed consent to voluntary study participation
Exclusion Criteria:
- Subjects who meet any of the following criteria cannot participate in the study:
Current disease and medical history
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History or current evidence of hepatic encephalopathy
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Histologically confirmed HCC in ≥50% of the liver
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Severe ascites requiring treatment such as paracentesis
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History or current evidence of the following infections:
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Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
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Active hepatitis B (Subjects with negative HBV titer within 14 days prior to screening based on the site-specific criteria who have been treated with antivirals for ≥14 days prior to screening and are willing to maintain the antiviral therapy throughout the study will be allowed to be enrolled.)
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Active hepatitis C (Patients who have completed antiviral therapy with negative HCV virial load based on the site-specific criteria will be allowed to be enrolled.)
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Uncontrolled severe chronic infection or active infection
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Prior or planned organ transplantation during the study period
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Diagnosis of any malignant tumor other than the study indication within 5 years prior to screening (Patients who were treated and assessed as complete response [CR] without recurrence within 3 years or patients diagnosed with nonmelanoma skin cancer, in-situ disease, thyroid cancer, or borderline tumor will be allowed to be enrolled.)
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Clinically significant, severe cardiac disease based on the judgment of the investigator (e.g., uncontrolled hypertension, congestive heart failure [NYHA Grade ≥2], ventricular arrhythmia, active ischemic heart disease, history of myocardial infarction within 1 year prior to screening), renal impairment, or respiratory disease
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Eutilex
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- EU-CTS307-I-01