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

Aeon Therapeutics

Status and phase

Terminated

Phase 1

Conditions

Liver Neoplasms

Metastatic Liver Cancer

Hepatocellular Carcinoma

Liver Cancer

Treatments

Biological: autologous ET1402L1-CART cells

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT03349255

ETCH17AFPCAR101

Details and patient eligibility

About

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

Full 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.

Enrollment

3 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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