To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307

Sponsor

Eutilex (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05783570

Collaborator

(none)

Enrollment

Arm

19.1

Anticipated Duration (Months)

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
Advanced Hepatocellular Carcinoma	Biological: EU307 CAR-T Cell	Phase 1

Detailed Description

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2023

Anticipated Primary Completion Date :

May 1, 2024

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EU307 CAR-T Cell	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

Arm

Intervention/Treatment

Experimental: EU307 CAR-T Cell

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

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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