ET1402L1-ARTEMIS™2 T Cells in Alpha Fetoprotein (AFP) Expressing Hepatocellular Carcinoma

NCT ID: NCT03888859

Last Updated: 2021-03-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

EARLY_PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-12-06

Study Completion Date

2020-12-08

Brief Summary

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Clinical study to evaluate safety (primary objectives) and efficacy (secondary objective) of ET1402L1-ARTEMIS™2 T cells in patients with alpha fetoprotein positive (AFP+ ) hepatocellular carcinoma (HCC).

Detailed Description

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The molecular target for ET1402L1-ARTEMIS™2 is human leukocyte antigen (HLA) -A02 complexed with a HLA-A02-restricted peptide of alpha fetoprotein (AFP), which is expressed on 60-80 percent of hepatocellular carcinoma (HCC). ARTEMIS™2 is a second generation ARTEMIS™ receptor engineered with a human antibody domain against the anti-HLA-A02/AFP complex. This clinical study evaluates the safety and pharmacokinetics of ET1402L1-ARTEMIS™2 T-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 intra-hepatic artery (IA) arm or Intratumoral Injections arm, with the ET1402L1-ARTEMIS™2 T-cells administered via intrahepatic artery catheter. Patients with extrahepatic metastasis will be enrolled in the intravenous (IV) arm, with the ET1402L1-ARTEMIS™2 T-cells administered through intravenous infusion.

Conditions

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Hepatocellular Carcinoma Liver Cancer Liver Neoplasms Metastatic Liver Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Intravenous (i.v.) arm

autologous ET1402L1-ARTEMIS™2 T cells administered by intravenous (IV) infusion

Group Type EXPERIMENTAL

ET1402L1-ARTEMIS™ T cells -IV

Intervention Type BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct -intravenous (i.v.) arm

Intra-hepatic artery (i.a.) arm

autologous ET1402L1-ARTEMIS™2 T cells administered by intra-hepatic artery (IA) infusion

Group Type EXPERIMENTAL

ET1402L1-ARTEMIS™ T cells -intra-hepatic artery

Intervention Type BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: intra-hepatic artery (i.a.) arm

Intratumoral Injections (i.t.) arm

autologous ET1402L1-ARTEMIS™2 T cells administered by intratumoral injections (i.t.) infusion

Group Type EXPERIMENTAL

ET1402L1-ARTEMIS™ T cells -Intratumoral Injections

Intervention Type BIOLOGICAL

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: Intratumoral Injections (i.t.) arm

Interventions

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ET1402L1-ARTEMIS™ T cells -IV

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct -intravenous (i.v.) arm

Intervention Type BIOLOGICAL

ET1402L1-ARTEMIS™ T cells -intra-hepatic artery

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: intra-hepatic artery (i.a.) arm

Intervention Type BIOLOGICAL

ET1402L1-ARTEMIS™ T cells -Intratumoral Injections

Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct: Intratumoral Injections (i.t.) arm

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* AFP-expressing HCC and serum AFP \>100 ng/mL.
* Abandon or failure in first or second line treatment
* Molecular HLA class I typing confirms participant carries at least one HLA-A02 allele
* Child-Pugh score of A or B, Barcelona Clinic Liver Cancer stage of C or D
* Life expectancy \> 4 months
* Karnofsky score ≥70%
* Adequate organ function as defined below:

1. Patients must have a serum Total bilirubin ≤2 x Upper Limit of Normal (ULN), Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤5 times the institutional ULN.
2. A pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute
3. Ejection fraction measured by echocardiogram or Multiple gated acquisition scanning (MUGA) \>45% (evaluation done with 6 weeks of screening does not need to be repeated)
4. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1)\>45% predicted
5. Absolute neutrophil count (ANC) ≥ 1500/mm3 (10\^9/L)
6. Platelet count ≥ 50,000/mm3 (10\^9/L)
* 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 tumor infiltration in the portal vein, hepatic veins or inferior vena cava that completely blocks circulation in liver.
* Patients with an organ transplantation history
* 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)
* 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.
* Women who are pregnant or breast-feed
* HIV-infection
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eureka Therapeutics Inc.

INDUSTRY

Sponsor Role collaborator

Aeon Therapeutics (Shanghai) Co., Ltd.

INDUSTRY

Sponsor Role collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Chang Liu, PhD

Role: PRINCIPAL_INVESTIGATOR

First Affiliated Hospital Xi'an Jiaotong University

Locations

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The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, , China

Site Status

Countries

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China

Other Identifiers

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XJTU1AF2017LSL-C002

Identifier Type: -

Identifier Source: org_study_id

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