Autologous HBV-specific T Cell Receptor Engineered T Cells (TCR-T) in Patients With HBV-related Advanced HCC

Study Overview
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Brief Summary
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Adoptive cell therapy with TCR-T cells targeting HBV antigens represents an innovative opportunity for treatment of HBV-related HCC. SCG101 is a genetically modified autologous TCR-T cell therapy with a natural high-avidity TCR directed towards the HLA-A*02-restricted HBsAg peptide. This is a phase 1 clinical study of SCG101 alone and with PD-1/PD-L1 checkpoint inhibitors in HBV-related HCC.

Detailed Description
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This is an open-label, multi-center clinical study to evaluate the safety, tolerability and effectiveness of SCG101, with and without PD-1/PD-L1 checkpoint inhibitors, in patients with HBV-related HCC. Lymphodepleting regimen of cyclophosphamide and fludarabine will be given prior to SCG101 infusion.

Official Title
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A Phase 1 Clinical Study of Autologous HBV-specific TCR-T Cell Therapy (SCG101) in Patients With HBV-related HCC

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Genetic: SCG101
* Biological: PD1/PD-L1 checkpoint inhibitor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed, or imaging diagnosed HCC HLA-A *02 genotyping HBsAg positive in serum or tumor tissue Have at least one measurable lesion at baseline as per mRECIST and RECIST v1.1 criteria Child-Pugh score ≤ 7 ECOG performance status of 0 or 1 Life expectancy of 3 months or greater Patient with adequate organ function Exclusion Criteria: Uncontrolled portal vein or inferior vena cava tumor thrombosis Untreated or active Central nervous system (CNS) metastasis or other clinically significant CNS diseases Active or uncontrollable infections History of organ transplantation Lack of peripheral or central venous access or any condition that would interfere with study drug administration or collection of study sample History of positive results for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS) Prior exposure to any cell therapy Other severe medical conditions that may limit subject's participation in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCG101<br>SCG101 will be given via Intravenous (IV) infusion. | Genetic: SCG101<br>* SCG101 is an autologous HBV-specific T cell receptor engineered T cell therapy.<br>|
| Experimental: SCG101 + PD1/PD-L1 checkpoint inhibitor<br>SCG101 will be given via Intravenous (IV) infusion. The PD-1/PD-L1 checkpoint inhibitor will be given per product label. | Genetic: SCG101<br>* SCG101 is an autologous HBV-specific T cell receptor engineered T cell therapy.<br>Biological: PD1/PD-L1 checkpoint inhibitor<br>* Commercially approved for HCC treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events (AEs) and laboratory abnormalities defined as dose limiting toxicities (DLT) | To assess the tolerability of SCG101 and determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: antitumor activity of SCG101 in subjects with HBV-related HCC | Tumor response assessment in accordance with mRECIST and iRECIST | Up to 2 years | 
| Efficacy: antiviral activity of SCG101 | Changes in serum levels of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA) before and after SCG101 infusion | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC