ECT204 T-Cell Therapy in Adults With Advanced HCC

Study Overview
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Brief Summary
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This will be an open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety of ECT204 T-cell therapy and determine the RP2D in adult subjects (≥ 18 years of age) who have GPC3-positive HCC and have failed or not tolerated at least two (2) different anti-HCC systemic agents.

Detailed Description
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The purpose of this study is to investigate an autologous T-cell therapy for advanced hepatocellular carcinoma (HCC). ECT204 T cells are autologous T cells genetically modified to carry a construct capable of mediating cell killing by targeting tumor specific antigens.

Official Title
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An Open-Label, Dose Escalation, Multi-Center Phase I/II Clinical Trial of ECT204 T-Cell Therapy in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-3)

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

Intervention / Treatment
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* Biological: ECT204 T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed HCC, which is unresectable, recurrent and/or metastatic. GPC3-positive expression in HCC tumor cells by immunohistochemistry (IHC). Must have failed or not tolerated at least two (2) different anti-HCC systemic agents. Life expectancy of at least 4 months per Principal Investigator's opinion. Karnofsky Performance Scale ≥ 70. Measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v.1.1). Previously treated lesions are allowed as long as there is a new confirmed measurable component. Child-Pugh score of A6 or better. Adequate organ function. Exclusion Criteria: Clinically significant pre-existing illness (e.g., heart failure) Active, uncontrolled systemic bacterial, fungal, or viral infection Active malignancy other than HCC, with the exception of cholangiocarcinoma (CCA) without any organ involvement and with an expected survival greater than or equal to 3 years without any treatment (exception: hormone/androgen- deprivation therapy) Currently receiving or ending (< 14 days from date of consent) liver tumor-directed therapy (e.g., radiation, ablation, embolization), or hepatic surgery. Active autoimmune disease requiring therapy Compromised circulation in portal vein, hepatic vein, or vena cava due to obstruction History of organ transplant Advanced HCC involving greater than half (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: ECT204<br>Approximately twelve (12) subjects will be treated to determine the RP2D. | Biological: ECT204 T cells<br>* ECT204 is an autologous T-cell therapy whereby a subject's own T cells are transduced with a lentiviral vector expressing the ECT204 transgene.<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 ECT204 T cells | Safety of ECT204 T cells as assessed by the number of adverse events (AEs) after infusion. | 28 days | 
| Severity rates of adverse events (AEs) after infusion of ECT204 T cells | Safety of ECT204 T cells as assessed by the severity of adverse events (AEs) after infusion. | 28 days | 
| Incidence rates of dose limiting toxicities (DLTs) after infusion of ECT204 T cells | Tolerability of ECT204 T cells after infusions assessed by committee review of dose limiting toxicities (DLTs) | 28 days | 
| The recommended phase 2 dose (RP2D) of ECT204 T cells | The RP2D will be determined by the study Dose Escalation Committee (DEC) and chosen based on the maximum tolerated dose (MTD) but will not exceed the MTD and the maximum administered dose (MAD). | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the efficacy of ECT204 T cells in subjects with advanced HCC by radiographic scans assessed according to RECIST and iRECIST criteria. | Response rate will be assessed by radiographic scans and assessed according to RECIST and iRECIST criteria. | Up to 2 years | 
| Determine the Maximum Concentration (Cmax) of ECT204 T cells in blood after infusion. | Determine the degree of expansion of ECT204 T cells after infusion. | Up to 2 years | 
| Determine the Time of Maximum Concentration (Tmax) of ECT204 T cells in blood after infusion. | Determine the expansion kinetics of ECT204 T cells after infusion. | Up to 2 years | 
| Determine the Area under the curve (AUC) at fixed time intervals (e.g., from Day 0 to Day 28). | Assess the expansion and persistence of ECT204 T cells after infusion. | 28 days | 

 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