Study of ET140202 T Cells in Adults With Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This is a open-label, dose escalation, multi-center, Phase I / Phase II study to assess the safety of an autologous T-cell product (ET140202) in adult subjects with advanced Alpha-fetoprotein (AFP) positive/Human Leukocyte Antigen (HLA) A-2 positive Hepatocellular Carcinoma (HCC).

Detailed Description
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The purpose of this study is to investigate a genetically modified autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ET140202 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 ET140202 T Cells and Determine the Recommended Phase II Dose (RP2D) in Adults With Advanced Hepatocellular Carcinoma (HCC)

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

Intervention / Treatment
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* Biological: ET140202 autologous T cell product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent obtained prior to study procedures Histologically confirmed HCC with serum AFP >200ng/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 one line of systemic therapy for advanced HCC 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 A or B7 Absolute neutrophil count greater than or equal to 1,500/mm^3 Platelet count greater than or equal to 30,000/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 unless expected survival is greater than or equal to three years without any treatment (exception: hormone/androgen-depravation 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 one-third 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ET140202 T cells<br>ET140202 Receptor (+) T Cells | Biological: ET140202 autologous T cell product<br>* Autologous T cells transduced with lentivirus encoding an ET140202 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 ET140202 T cells | Safety and tolerability of ET140202 T cells as assessed by committee review of dose limiting toxicities (DLTs) and incidence and severity of adverse events (AEs) after infusion | 28 days | 
| The recommended phase 2 dose (RP2D) regimen of ET140202 T-cell therapy | 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 efficacy of ET140202 T cells by overall response rate (ORR) using Response Evaluation Criteria In Solid Tumors (RECIST). | As a measure of activity, overall response rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Assess efficacy of ET140202 T cells by complete response (CR) using Response Evaluation Criteria In Solid Tumors (RECIST). | As a measure of activity, CR rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Assess efficacy of ET140202 T cells by partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST). | As a measure of activity, PR rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Assess efficacy of ET140202 T cells by progression-free survival (PFS) using Response Evaluation Criteria In Solid Tumors (RECIST). | As a measure of activity, PFS rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Assess efficacy of ET140202 T cells by overall survival (OS) using Response Evaluation Criteria In Solid Tumors (RECIST). | As a measure of activity, OS rate will be assessed by radiographic scans and assessed according to RECIST criteria. | up to 2 years | 
| Assess the expansion of ET140202 T cells in the blood shortly after infusion. | The maximum (peak) expansion of ET140202 T cells in the blood post infusion will be determined. | up to 2 years | 
| Assess the persistence of ET140202 T cells circulating in blood over time. | The level of ET140202 T cells in blood will be determined to assess the persistence of ET140202 T cells during the treatment and follow-up phases of the study. | 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