Clinical trial NCT03888859: ET1402L1-ARTEMIS™2 T Cells in Alpha Fetoprotein (AFP) Expressing Hepatocellular Carcinoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hepatocellular Carcinoma
Liver Cancer
Liver Neoplasms
Metastatic Liver Cancer
Lead sponsor: First Affiliated Hospital Xi'an Jiaotong University
Sponsor class: OTHER
Collaborators: name: Eureka Therapeutics Inc.
name: Aeon Therapeutics (Shanghai) Co., Ltd.
First posted: 2019-03-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with dose-limiting toxicity
timeFrame: 28 days up to 2 years
measure: Frequency of ARTEMIS T cell treatment-related adverse events
timeFrame: Time Frame: 28 days up to 2 years
Secondary outcomes:
measure: Rate of disease response by RECIST in the liver
timeFrame: 2 years
measure: Rate of disease response by RECIST at non-liver sites
timeFrame: 2 years
measure: Progression free survival (PFS)
timeFrame: at 4 months, 1 year, 2 years
measure: Median Survival（MS）
timeFrame: at 4 months, 1 year, 2 years
measure: Overall survival（OS）
timeFrame: at 2 years
measure: AFP serum levels
timeFrame: 2 years
measure: Number of ET1402L1-ARTEMIS™2 T cells in peripheral blood
timeFrame: 2 years
measure: % of ET1402L1-ARTEMIS™2 T cells in peripheral blood
timeFrame: 2 years
measure: AFP expression in tumors
timeFrame: 4-8 weeks
measure: Tmax of serum Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor(TNF)-α and Interferon gamma (INFγ)
timeFrame: 24 weeks
measure: AUC of serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ
timeFrame: 24 weeks
measure: Time to baseline for serum IL-2, IL-4, IL-6, IL-10, TNF-α and INFγ
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
Study officials:
affiliation: First Affiliated Hospital Xi'an Jiaotong University
name: Chang Liu, PhD
role: PRINCIPAL_INVESTIGATOR
References: