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

NCT03888859 | Completed Early Phase 1

• 1 other identifier: XJTU1AF2017LSL-C002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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-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

  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 Outcomes (12)

• Rate of disease response by RECIST in the liver

  2 years

• Rate of disease response by RECIST at non-liver sites

  2 years

• Progression free survival (PFS)

  at 4 months, 1 year, 2 years

• Median Survival（MS）

  at 4 months, 1 year, 2 years

• Overall survival（OS）

  at 2 years

Study Arms (3)

Intravenous (i.v.) arm

EXPERIMENTAL

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

Biological: ET1402L1-ARTEMIS™ T cells -IV

Intra-hepatic artery (i.a.) arm

EXPERIMENTAL

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

Biological: ET1402L1-ARTEMIS™ T cells -intra-hepatic artery

Intratumoral Injections (i.t.) arm

EXPERIMENTAL

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

Biological: ET1402L1-ARTEMIS™ T cells -Intratumoral Injections

Interventions

ET1402L1-ARTEMIS™ T cells -IV BIOLOGICAL

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

Intravenous (i.v.) arm

ET1402L1-ARTEMIS™ T cells -intra-hepatic artery BIOLOGICAL

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

Intra-hepatic artery (i.a.) arm

ET1402L1-ARTEMIS™ T cells -Intratumoral Injections BIOLOGICAL

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

Intratumoral Injections (i.t.) arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• A pretreatment measured creatinine clearance (absolute value) of ≥ 50 ml/minute
• 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)
• Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) or Forced Expiratory Volume in the first second (FEV1)\>45% predicted
• Absolute neutrophil count (ANC) ≥ 1500/mm3 (10\^9/L)
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• First Affiliated Hospital Xi'an Jiaotong University: lead
• Eureka Therapeutics Inc.: collaborator
• Aeon Therapeutics (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, 710061, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Chang Liu, PhD

  First Affiliated Hospital Xi'an Jiaotong University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 1, 2019
• First Posted: March 25, 2019
• Study Start: December 6, 2017
• Primary Completion: April 13, 2019
• Study Completion: December 8, 2020
• Last Updated: March 29, 2021

Record last verified: 2021-03

Locations

CN (1)