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Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)

Phase 1
Terminated
Conditions
Liver Cancer
Hepatocellular Carcinoma
Liver Neoplasm
Metastatic Liver Cancer
Interventions
Biological: ET140203 autologous T cell product
Registration Number
NCT04502082
Lead Sponsor
Eureka Therapeutics Inc.
Brief Summary

Open-label, dose escalation, multi-center, Phase I / II study to assess the safety of an autologous T-cell product (ET140203) in adult subjects with Alpha-fetoprotein (AFP)-positive/Human Leukocyte Antigen (HLA) A-2-positive advanced hepatocellular carcinoma (HCC).

Detailed Description

The purpose of this study is to investigate an autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140203 T cells are autologous T cells genetically modified to carry a TCR-mimic (TCRm) construct capable of mediating cell killing by targeting tumor specific intracellular antigens and addressing solid tumor therapy challenges.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
6
Inclusion Criteria
  • Histologically confirmed HCC with serum AFP >100ng/ml at time of screening and following most current line of therapy OR radiographic diagnosis of HCC with serum AFP >400ng/ml at time of screening and following most current line of therapy.
  • Metastatic or locally advanced, unresectable HCC
  • Must have failed or not tolerated at least two (2) different anti-HCC systemic agents
  • Molecular Human Leukocyte Antigen ("HLA") class I allele typing confirms participant carries at least one HLA-A2 allele
  • Life expectancy of at least 4 months
  • Karnofsky Performance Scale greater than or equal to 70
  • At least 1 measurable lesion on imaging by RECIST
  • Child-Pugh A6 or better
  • Absolute neutrophil count greater than or equal to 1,500/mm^3
  • Platelet count greater than or equal to 75,000/mm^3
Exclusion Criteria
  • Clinically significant cardiac disease
  • Clinically significant pre-existing illness or active infection
  • Clinically significant Central Nervous System (CNS) or neural dysfunction
  • Active autoimmune disease requiring therapy
  • Active malignancy other than HCC with the exception of cholangiocarcinoma (CCA) or any malignancy with an expected survival ≥ 3 years without any treatment (exception: hormone/androgen-deprivation therapy) and without any organ involvement
  • History of organ transplant
  • Compromised circulation in portal vein, hepatic vein, or vena cava due to obstruction
  • Advanced HCC involving greater than 50% of the liver

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
ET140203 TCellsET140203 autologous T cell productET140203 T Cells
Primary Outcome Measures
NameTimeMethod
The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLTup to 2 years

The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response

Incidence rates of adverse events (AEs) after infusion of ET140203 T cells28 days

Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion

Severity rates of adverse events (AEs) after infusion of ET140203 T cells28 days

Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.

Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells28 days

Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)

Secondary Outcome Measures
NameTimeMethod
Assess the efficacy of ET140203 T cells in adults with advanced HCC.up to 2 years

Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.

Determine the pharmacokinetics of ET140203 T cells after infusion.up to 2 years

Assess the persistence of ET140203 T cells circulating in blood over time

Trial Locations

Locations (2)

City of Hope Medical Center

🇺🇸

Duarte, California, United States

Kansas University Medical Center

🇺🇸

Westwood, Kansas, United States

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