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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT03349255
Other study ID # ETCH17AFPCAR101
Secondary ID
Status Terminated
Phase Phase 1
First received
Last updated
Start date October 6, 2017
Est. completion date January 10, 2019

Study information

Verified date June 2019
Source Aeon Therapeutics (Shanghai) Co., Ltd.
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


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/CD3ΞΆ) 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.


Recruitment information / eligibility

Status Terminated
Enrollment 3
Est. completion date January 10, 2019
Est. primary completion date January 10, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Study Design


Intervention

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

Locations

Country Name City State
China Renmin Hospital of Wuhan University Wuhan Hubei

Sponsors (3)

Lead Sponsor Collaborator
Aeon Therapeutics (Shanghai) Co., Ltd. Eureka Therapeutics Inc., Renmin Hospital of Wuhan University

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of patients with dose-limiting toxicity A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET1402L1-CART-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits. 28 days up to 2 years
Primary Toxicity profile of ET1402L1-CART-cell treatment Frequency of treatment-related adverse events that occurred at any time from the first day of infusion that are "possibly", "likely", or "definitely" related to the study, including infusion related toxicity and ET1402L1-CART T cells related toxicity. Include but not limited to: Fever, chills, nausea, vomiting, jaundice and other gastrointestinal symptoms; Fatigue, hypotension, respiratory distress; Tumor lysis syndrome; Cytokine release syndrome; Neutropenia, thrombocytopenia; Liver and kidney dysfunction. Assessed at all visits. 28 days up to 2 years
Secondary Rate of disease response by RECIST in the liver Response rates will be estimated as the percent of patients with objective response (OR), complete remission (CR), partial response (PR), stable disease (SD), no response (NR), overall survival (OS). 2 years
Secondary Rate of disease response by RECIST at non-liver sites Response rates will be estimated as the percent of patients with objective response (OR), complete remission (CR), partial response (PR), stable disease (SD), no response (NR), overall survival (OS). 2 years
Secondary Anti-tumor responses Progression free survival (PFS) and Median survival (MS) at 4 months, 1 year, 2 years 4 months, 1 year, 2 years
Secondary AFP serum levels Percent change compared to the baseline 2 years
Secondary CART cell engraftment Number and % of ET1402L1-CART cells in peripheral blood will be presented as Time to peak, Time to baseline level and the overall exposure will be presented as area under curve (AUC). 2 years
Secondary AFP expression in tumors Percent of AFP-positive cells in randomly selected fields in tumor biopsies 4-8 weeks
Secondary Tmax of serum cytokine levels Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as time to peak level. 24 weeks
Secondary Time to baseline for serum cytokine levels Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as Time to baseline. 24 weeks
Secondary AUC of serum cytokine levels Increases or decreases in the amount of cytokine produced compared to baseline at time points measured up to 24 weeks since dosing. Cytokines as measured by Bio-Plex Multiplex Immuoassays will be presented as area under curve (AUC). 24 weeks
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