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

NCT03349255 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ETCH17AFPCAR101
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Keywords

alpha-fetoprotein; AFP; HCC; CAR T cell therapy

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-CART-cells, which is irreversible, or life threatening or CTCAE Grade 3-5. Assessed at all visits.

  28 days up to 2 years

• 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 Outcomes (9)

• Rate of disease response by RECIST in the liver

  2 years

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

  2 years

• Anti-tumor responses

  4 months, 1 year, 2 years

• AFP serum levels

  2 years

• CART cell engraftment

  2 years

Study Arms (2)

intravenous (i.v.) arm

EXPERIMENTAL

autologous ET1402L1-CART cells administered by intravenous (IV) infusion

Biological: autologous ET1402L1-CART cells

intra-hepatic artery (i.a.) arm

EXPERIMENTAL

autologous ET1402L1-CART cells administered by intra-hepatic artery (IA) infusion

Biological: autologous ET1402L1-CART cells

Interventions

autologous ET1402L1-CART cells BIOLOGICAL

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

intra-hepatic artery (i.a.) arm; intravenous (i.v.) arm

Eligibility Criteria

• Age: 18 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Aeon Therapeutics (Shanghai) Co., Ltd.: lead
• Renmin Hospital of Wuhan University: collaborator
• Eureka Therapeutics Inc.: collaborator

Study Sites (1)

Renmin Hospital of Wuhan University

Wuhan, Hubei, 430060, 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

• Qibin Song, M.D./Ph.D.

  Renmin Hospital of Wuhan University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 24, 2017
• First Posted: November 21, 2017
• Study Start: October 6, 2017
• Primary Completion: January 10, 2019
• Study Completion: January 10, 2019
• Last Updated: July 1, 2019

Record last verified: 2019-06

Locations

CN (1)