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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Genetic: SCG101; Biological: PD1/PD-L1 checkpoint inhibitor

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 Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Shunda Du, Doctor; Phone Number: +86-10-69156114; Email: dushd@pumch.cn
• Study Contact Backup: Name: Yong Pang; Phone Number: +8613601248748; Email: yong.pang@dastarpharma.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • Peking Union Medical College Hospital
    • Contact: Shunda Du
  • Shanghai, China
    • Recruiting
    • Zhongshan hospital, Fudan university
    • Contact: Yuhong Zhou, Doctor
  • Shenyang, China
    • Recruiting
    • The First Hospital of China Medical University
    • Contact: Yunpeng Liu
  • Shenyang, China
    • Recruiting
    • The Sixth People's Hospital of Shenyang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCG101; SCG101 will be given via Intravenous (IV) infusion.	Genetic: SCG101; SCG101 is an autologous HBV-specific T cell receptor engineered T cell therapy.
Experimental: SCG101 + 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.	Genetic: SCG101; SCG101 is an autologous HBV-specific T cell receptor engineered T cell therapy.; Biological: PD1/PD-L1 checkpoint inhibitor; Commercially approved for HCC treatment.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Principal Investigator: Shunda Du, Peking Union Medical College Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2021
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: HCC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: SCG101-CI-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No