To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307

Study Overview
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Brief Summary
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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

Detailed Description
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A Dose-escalation, Single-arm, Open-Label, Phase 1 Study

Official Title
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A Dose-escalation, Single-arm, Open-Label, Phase 1 Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307, Autologous Glypican 3 Targeted Chimeric Antigen Receptor T Cell Therapy in Patients With GPC3 Positive Advanced Hepatocellular Carcinoma Who Have Failed Standard Therapy

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: EU307 CAR-T Cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible, subjects must meet all of the following criteria: Male or female adults ≥19 years old at the time of written informed consent 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). Confirmed GPC3 positivity by IHC based on a liver tissue sample At least 1 measurable lesion based on mRECIST v1.1 Child-Pugh score Class A or Class B(7) Life expectancy ≥3 months based on the judgment of the investigator ECOG PS 0 or 1 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 Negative serum pregnancy test in women of childbearing potential 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 History or current evidence of hepatic encephalopathy Histologically confirmed HCC in ≥50% of the liver Severe ascites requiring treatment such as paracentesis History or current evidence of the following infections: Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS) 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.) 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.) Uncontrolled severe chronic infection or active infection Prior or planned organ transplantation during the study period 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.) 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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EU307 CAR-T Cell<br> | Biological: EU307 CAR-T Cell<br>* Dose to be administered: a single dose IV administration Dosing rate: To be administrated at a rate of approximately 2 mL/min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs (including DLT) | 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 | up to 6 month from LPI | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Proportion of subjects with confirmed CR or partial response (PR) as best overall response (BOR) | up to 6 month | 
| DoR | Time from confirmed tumor response (CR or PR) to confirmed progressive disease (PD) | up to 6 month | 
| DCR | Proportion of subjects with confirmed CR, PR, or stable disease (SD) (≥ 6 weeks) as BOR | up to 6 month | 
| TTR | Time from IP dosing to confirmed objective response (CR or PR) | up to 6 month | 
| TTP | Time from IP dosing to PD | up to 6 month | 
| PFS | Time from IP dosing to PD or all-cause death, whichever is earlier | up to 6 month | 
| OS | Time from IP dosing to all-cause death | up to 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GPC3, HCC, Hepatocellular Carcinoma, CAR-T