Clinical Study of ET1402L1-CAR T Cells in AFP Expressing Hepatocellular Carcinoma

NCT ID: NCT03349255

Last Updated: 2019-07-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-06
• Study Completion Date: 2019-01-10

Brief Summary

Clinical study to evaluate safety and pharmacokinetics (primary objectives) and efficacy (secondary objective) of ET1402L1-CART-cells in patients with AFP+ HCC

Detailed Description

The molecular target for ET1402L1-CART is alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ET1402L1-CART is a second generation (CD28/CD3ζ) chimeric antigen receptor (CAR) engineered with a human single-chain variable antibody fragments (scFv) against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-CART-cells in patients with HCC who have no available curative therapeutic options and a poor overall prognosis.

Patients with lesion(s) localized in liver will be enrolled in the IA arm, with the ET1402L1-CART-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the IV arm, with the ET1402L1-CART-cells administered through intravenous infusion.

Conditions

Hepatocellular Carcinoma; Liver Cancer; Liver Neoplasms; Metastatic Liver Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

intravenous (i.v.) arm

autologous ET1402L1-CART cells administered by intravenous (IV) infusion

Group Type: EXPERIMENTAL

autologous ET1402L1-CART cells

Intervention Type: BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1)-CAR expression construct

intra-hepatic artery (i.a.) arm

autologous ET1402L1-CART cells administered by intra-hepatic artery (IA) infusion

Group Type: EXPERIMENTAL

autologous ET1402L1-CART cells

Intervention Type: BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1)-CAR expression construct

Interventions

autologous ET1402L1-CART cells

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1)-CAR expression construct

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• AFP-expressing HCC and serum AFP >100 ng/mL.
• Measurable disease as defined by: at least 1 liver lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 20 mm.
• Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
• Child-Pugh score of A or B
• Life expectancy > 4 months
• Age at time of enrollment is ≥18 years of age.
• KPS ≥70%
• Adequate organ function as defined below:

• A pretreatment measured creatinine clearance (absolute value) of ≥50 ml/minute.
• Patients must have a serum direct bilirubin ≤2 x ULN, ALT and AST ≤5 times the institutional upper limits of normal.
• Ejection Fraction measured by echocardiogram or MUGA >45% (evaluation done within 6 weeks of screening does not need to be repeated)
• DLCO or FEV1 >45% predicted
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (10^9/L)
• Platelet count ≥ 50,000/mm3 (10^9/L)
• Negative serum pregnancy test for women with childbearing potential
• Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria

• Patients with decompensated cirrhosis: Child-Pugh Score C
• Patients with an organ transplantation history
• Patients with tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
• Patients with dependence on corticosteroids
• Patients with active autoimmune diseases requiring systemic immunosuppressive therapy
• Patients who are currently receiving or received within past 30 days anti-cancer therapy, local treatments for liver tumors (radiotherapy, embolism, ablation) or liver surgery
• Patients currently receiving other investigational treatments (biotherapy, chemotherapy, or radiotherapy)
• Patients undergoing current treatment known to interfere with lymphodepleting chemotherapy (cyclophosphamide, etc.).
• Participants with other active malignancies (except non-melanoma skin cancer and cervical cancer) within two years. Patients with a history of successfully-treated tumors with no sign of recurrence in the last two years may be enrolled.
• Patients with other uncontrolled diseases, such as active infections:

• Acute or chronic active hepatitis B or hepatitis C.
• HIV-infection
• Women who are pregnant

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Renmin Hospital of Wuhan University

OTHER

Sponsor Role: collaborator

Eureka Therapeutics Inc.

INDUSTRY

Sponsor Role: collaborator

Aeon Therapeutics (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qibin Song, M.D./Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Renmin Hospital of Wuhan University

Locations

Renmin Hospital of Wuhan University

Wuhan, Hubei, China

Countries

China

Other Identifiers

ETCH17AFPCAR101

Identifier Type: -

Identifier Source: org_study_id