A Study of SCG101 in the Treatment of Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This Phase 1/ 2a study is a multicenter study to evaluate the safety, tolerability and efficacy of SCG101 in subjects with hepatitis B virus-related hepatocellular carcinoma

Detailed Description
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This study will be conducted in 2 parts: In Phase 1 dose escalation, cohorts of 3-6 subjects each will be sequentially assigned to escalating dose level of SCG101. The recommended phase 2 dose (RP2D) will be selected based on the safety, PK/ PD and antitumor activities if the maximum tolerated dose (MTD) is not reached from the planned dose levels. In Phase 2a, subjects will be enrolled to characterize the safety and evaluate the efficacy of SCG101.

Official Title
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A Phase 1/ 2a, Multicenter Study of SCG101 in the Treatment of Subjects With Hepatitis B Virus-Related Hepatocellular Carcinoma

Conditions
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Hepatitis B Virus Related Hepatocellular Carcinoma, Hepatocellular Carcinoma Recurrent

Intervention / Treatment
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* Biological: SCG101


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histologically or cytologically confirmed Hepatocellular carcinoma (HCC) Subjects with HCC who have received at least 2 standard systemic therapies HLA-A *02 BCLC stage B or C Child-pugh score ≤ 7 Serum HBeAg negative, serum (or tumor tissue) HBsAg positive, and serum HBV-DNA must be 2 × 1000 IU/ml Have at least one measurable leasion at baseline as per mRECIST and RECIST v1.1 criteria Life expectancy of 3 months or greater Ability to provide informed consent form Ability to comply with all the study procedures Main Exclusion Criteria: Subjects with history of another primary cancer Untreated or active central nervous system (CNS) or leptomeningeal metastasis, or history of hepatic encephalopathy, or other clinically significant CNS diseases Autoimmune diseases requiring immunosuppressive therapy (except topical medication) or subjects with significant persistent immune rejection Known history of neurological or mental disorder, including epilepsy or dementia Known history of positive results for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS) Prior exposure to any cell therapy such as, but not limited to killer (NK) cells, cytokine-induced killer (CIK) cells, dendritic cells (DC), cytotoxic T lymphocytes (CTL), stem cell therapy, CAR T/TCR T cell therapy Allergy to immunotherapy drugs and lymphodepleting chemotherapy (cyclophosphamide and fludarabine) Any subjects who cannot be evaluated by either triphasic liver CT or triphasic MRI because of allergy or other contraindication to both CT and MRI contrast agents Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation

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
Intervention Model: Single Group Assignment
Interventional Model Description: SCG101 in the Treatment of Subjects with Hepatitis B Virus-Related Hepatocellular Carcinoma
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCG101<br>This is a single arm study. Patients will receive infusion and will be observed for dose limiting toxicity (DLT) over a 28-day period, and thereafter enter the progression free survival observation period and continuous long term survival follow up at time of disease progression. | Biological: SCG101<br>* Infusion of HBsAg-specific TCR autologous T cells at assigned dose levels.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of SCG101 | Based on incidence of adverse events (AE) using NCI-CTCAE v5.0 | Start of SCG101 infusion until 100 days post SCG101 infusion | 
| Tumor response of SCG101 (Phase 2) |  | Start of SCG101 infusion until a complate response or partial response is observed, disease progression, and long term survival follow up up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary clinical efficacy of SCG101 | Objective response rate | Start of SCG101 infusion until a complete response or partial response is observed after 28 days from SCG101 infusion. | 
| Antiviral activity before and after SCG101 infusion | Based on changes in serum levels of HBsAg | Start of SCG101 infusion and throughout DLT and PFS until disease progression, an average of 24 months. | 
| Change in pharmacodynamic markers (PD) before and after SCG101 infusion | Based on changes in serum from the liver function | Start of SCG101 infusion and throughout DLT and PFS until disease progression, an average of 24 months. | 
| Persistence of viral vector copy number (VCN) after SCG101 infusion |  | Start of SCG101 infusion until disease progression, an average of 24 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC, Hepatitis B Virus Related, HCC Recurrent