To Evaluate the Safety, Tolerability and Preliminary Efficacy of EU307

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05783570
• Other study ID #: EU-CTS307-I-01
• Status: Recruiting
• Phase: Phase 1
• Start date: August 24, 2023
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Eutilex
• Contact: subin kim
• Phone: +82-2-2071-3310
• Email: sbkim[@]eutilex.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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 = 5?ULN 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

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	SoonChunHyang University Hospital Seoul	Seoul
Korea, Republic of	The Catholic University of Korea Seoul ST.MARY'S Hospital.	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Eutilex

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quantitative CAR-T DNA assay		up to 6 month
Other	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
Primary	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
Primary	Production of replication competent lentiviruses (RCL)		up to 6 month from LPI
Primary	Development of anti-drug antibodies (ADA)		up to 6 month from LPI
Secondary	ORR	Proportion of subjects with confirmed CR or partial response (PR) as best overall response (BOR)	up to 6 month
Secondary	DoR	Time from confirmed tumor response (CR or PR) to confirmed progressive disease (PD)	up to 6 month
Secondary	DCR	Proportion of subjects with confirmed CR, PR, or stable disease (SD) (= 6 weeks) as BOR	up to 6 month
Secondary	TTR	Time from IP dosing to confirmed objective response (CR or PR)	up to 6 month
Secondary	TTP	Time from IP dosing to PD	up to 6 month
Secondary	PFS	Time from IP dosing to PD or all-cause death, whichever is earlier	up to 6 month
Secondary	OS	Time from IP dosing to all-cause death	up to 6 month