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

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.

The trial was intended to be a Phase 1/2 trial, but the sponsor terminated the trial prior to moving to Phase 2 to direct their efforts to the pediatric study (ARYA-2) for this product.

• ET140203 autologous T cell product (Biological): Autologous T cells transduced with lentivirus encoding an ET140203 expression construct

Primary outcomes

• Incidence rates of adverse events (AEs) after infusion of ET140203 T cells [28 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 cells [28 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 cells [28 days]: Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
• The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT [up 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

Secondary outcomes

• 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

Sex: All, ages: 18 Years to any

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

• Pei Wang, PhD, Study director, Eureka Therapeutics Inc.