To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307

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

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

Study Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Biological: EU307 CAR-T Cell

Detailed Description

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

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: subin kim; Phone Number: +82-2-2071-3310; Email: sbkim@eutilex.com

Study Locations

• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of
    • Recruiting
    • National Cancer Center
    • Contact: Bo-Hyun Kim, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
    • Contact: Do-Young Kim, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Soonchunhyang University Hospital Seoul
    • Contact: Jae-Young Jang, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • The Catholic University of Korea Seoul ST.MARY'S Hospital.
    • Contact: Pil-Soo Sung, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• To be eligible, subjects must meet all of the following criteria:

  1. Male or female adults ≥19 years old at the time of written informed consent

  2. 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).

  3. Confirmed GPC3 positivity by IHC based on a liver tissue sample
  4. At least 1 measurable lesion based on mRECIST v1.1
  5. Child-Pugh score Class A or Class B(7)
  6. Life expectancy ≥3 months based on the judgment of the investigator
  7. ECOG PS 0 or 1

  8. 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 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

  9. Negative serum pregnancy test in women of childbearing potential

  10. 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)

  11. 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

1. History or current evidence of hepatic encephalopathy
2. Patients with radiographic findings of brain metastases or spinal cord compression
3. Histologically confirmed HCC in ≥50% of the liver
4. Severe ascites requiring treatment such as paracentesis

5. History or current evidence of the following infections:

   • Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
   • Active hepatitis B (However, if HBsAg is positive, and if it is low or undetectable HBV DNA (HBV DNA level <2,000 IU/mL) based on the site-specific criteria at screening and a prophylactic antiviral agent can be administered for 6 months after the administration of the investigational product, enrollment is possible at the discretion of the investigator.)
   • Active hepatitis C (However, patients who have undergone antiviral therapy and whose HCV viral load is negative based on the site-specific criteria will be allowed to be enrolled.)
   • Uncontrolled severe chronic infection or active infection
6. Prior or planned organ transplantation during the study period
7. 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.)
8. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative CAR-T DNA assay		up to 6 month
Immunological assessment	-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	up to 6 month

Collaborators and Investigators

• Sponsor: Eutilex

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: February 27, 2023
• First Submitted That Met QC Criteria: March 13, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; CAR-T; GPC3
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: EU-CTS307-I-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No