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

Phase 1

• Conditions: Hepatocellular Carcinoma
• Interventions: Genetic: SCG101; Biological: PD1/PD-L1 checkpoint inhibitor

• Registration Number: NCT05339321
• Lead Sponsor: Peking Union Medical College Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2021-04-14
• Status Verified: 2022-04
• Study First Submitted: 2022-04-14
• Study First Submitted QC: 2022-04-14
• Study First Posted: 2022-04-21
• Last Update Submitted: 2022-05-07
• Last Update Posted: 2022-05-10
• Primary Completion: 2023-07
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Histologically or cytologically confirmed, or imaging diagnosed HCC
2. HLA-A *02 genotyping
3. HBsAg positive in serum or tumor tissue
4. Have at least one measurable lesion at baseline as per mRECIST and RECIST v1.1 criteria
5. Child-Pugh score ≤ 7
6. ECOG performance status of 0 or 1
7. Life expectancy of 3 months or greater
8. Patient with adequate organ function

Exclusion Criteria

1. Uncontrolled portal vein or inferior vena cava tumor thrombosis
2. Untreated or active Central nervous system (CNS) metastasis or other clinically significant CNS diseases
3. Active or uncontrollable infections
4. History of organ transplantation
5. Lack of peripheral or central venous access or any condition that would interfere with study drug administration or collection of study sample
6. History of positive results for human immunodeficiency virus (HIV) 1 or 2 or known acquired immunodeficiency syndrome (AIDS)
7. Prior exposure to any cell therapy
8. Other severe medical conditions that may limit subject's participation in this trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
SCG101 + PD1/PD-L1 checkpoint inhibitor	PD1/PD-L1 checkpoint inhibitor	SCG101 will be given via Intravenous (IV) infusion. The PD-1/PD-L1 checkpoint inhibitor will be given per product label.
SCG101	SCG101	SCG101 will be given via Intravenous (IV) infusion.
SCG101 + PD1/PD-L1 checkpoint inhibitor	SCG101	SCG101 will be given via Intravenous (IV) infusion. The PD-1/PD-L1 checkpoint inhibitor will be given per product label.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (4)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

Zhongshan Hospital, Fudan University; 🇨🇳 Shanghai, China

The Sixth People's Hospital of Shenyang; 🇨🇳 Shenyang, China

The First Hospital of China Medical University; 🇨🇳 Shenyang, China