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

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140203 T Cells and Determine the Recommended Phase II Dose (RP2D) in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-1)

Conditions
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Hepatocellular Carcinoma, Liver Cancer, Liver Neoplasm, Metastatic Liver Cancer

Intervention / Treatment
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* Biological: ET140203 autologous T cell product


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ET140203 TCells<br>ET140203 T Cells | Biological: ET140203 autologous T cell product<br>* Autologous T cells transduced with lentivirus encoding an ET140203 expression construct<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rates of adverse events (AEs) after infusion of ET140203 T cells | Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion | 28 days | 
| Severity rates of adverse events (AEs) after infusion of ET140203 T cells | Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion. | 28 days | 
| Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells | Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs) | 28 days | 
| The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT | The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of ET140203 T cells in adults with advanced HCC. | Response rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Determine the pharmacokinetics of ET140203 T cells after infusion. | Assess the persistence of ET140203 T cells circulating in blood over time | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma HCC, Advanced HCC, Late-Stage HCC, Liver Cancer, Liver Neoplasm, Metastatic Liver Cancer, Metastatic HCC, T-cell therapy, Immunotherapy