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

March 26, 2021 updated by: First Affiliated Hospital Xi'an Jiaotong University

Phase 1, Open-label, Three Routes IV, Intratumoral Injections and Intra-hepatic Artery Dose-escalation Clinical Study to Evaluate the Safety and Efficacy of ET1402L1-ARTEMIS™2™ T- Cells in AFP Expressing Hepatocellular Carcinoma (HCC)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Xi'an, China, 710061
        • The First Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: SEQUENTIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Intravenous (i.v.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intravenous (IV) infusion
Biological: ET1402L1-ARTEMIS™ T cells -IV
Autologous T cells transduced with lentivirus encoding an anti-AFP (ET1402L1) -ARTEMIS™2 expression construct -intravenous (i.v.) arm
EXPERIMENTAL: Intra-hepatic artery (i.a.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intra-hepatic artery (IA) infusion
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
EXPERIMENTAL: Intratumoral Injections (i.t.) arm
autologous ET1402L1-ARTEMIS™2 T cells administered by intratumoral injections (i.t.) infusion
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with dose-limiting toxicity
Time Frame: 28 days up to 2 years
A dose limiting toxicity is defined as any toxicity that is considered to be primarily related to the ET1402L1-ARTEMIS™2 T-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.
28 days up to 2 years
Frequency of ARTEMIS T cell treatment-related adverse events
Time Frame: Time Frame: 28 days up to 2 years
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.
Time Frame: 28 days up to 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
AFP serum levels
Time Frame: 2 years
Percent change compared to the baseline
2 years
Rate of disease response by RECIST in the liver
Time Frame: 2 years
Response rates will be estimated as the percent of patients with objective response (OR)，which was defined as any of complete remission (CR), partial response (PR) at 2 years.
2 years
Rate of disease response by RECIST at non-liver sites
Time Frame: 2 years
Response rates will be estimated as the percent of patients with objective response (OR)，which was defined as any of complete remission (CR), partial response (PR) at 2 years.
2 years
Progression free survival (PFS)
Time Frame: at 4 months, 1 year, 2 years
Progression free survival (PFS) at 4 months, 1 year and 2 years
at 4 months, 1 year, 2 years
Median Survival（MS）
Time Frame: at 4 months, 1 year, 2 years
Median Survival（MS）at 4 months, 1 year and 2 years
at 4 months, 1 year, 2 years
Overall survival（OS）
Time Frame: at 2 years
overall survival（OS）at 2 years
at 2 years
Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood
Time Frame: 2 years
Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level
2 years
% of ET1402L1-ARTEMIS™2 T cells in peripheral blood
Time Frame: 2 years
%of ET1402L1-ARTEMIS™2 T cells in peripheral blood will be presented as Time to peak, Time to baseline level
2 years
AFP expression in tumors
Time Frame: 4-8 weeks
Percent of AFP-positive cells in randomly selected fields in tumor biopsies.
4-8 weeks
Tmax of serum Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor(TNF)-α and Interferon gamma (INFγ)
Time Frame: 24 weeks
Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for Tmax.
24 weeks
AUC of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ
Time Frame: 24 weeks
Increase or decreases in the amount of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing. Data will be presented as time to peak level for area under curve (AUC).
24 weeks
Time to baseline for serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ
Time Frame: 24 weeks
Increase or decreases in the amount of IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ produced compared to baseline at time points measured up to 24 weeks since dosing.
24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

First Affiliated Hospital Xi'an Jiaotong University

Collaborators

Eureka Therapeutics Inc.
Aeon Therapeutics (Shanghai) Co., Ltd.

Investigators

  • Principal Investigator: Chang Liu, PhD, First Affiliated Hospital Xi'an Jiaotong University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

December 6, 2017

Primary Completion (ACTUAL)

April 13, 2019

Study Completion (ACTUAL)

December 8, 2020

Study Registration Dates

First Submitted

February 1, 2019

First Submitted That Met QC Criteria

March 22, 2019

First Posted (ACTUAL)

March 25, 2019

Study Record Updates

Last Update Posted (ACTUAL)

March 29, 2021

Last Update Submitted That Met QC Criteria

March 26, 2021

Last Verified

March 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XJTU1AF2017LSL-C002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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