TCR-Redirected T Cells Therapy in Patient With HBV Related HCC

This is a single center. single arm, open-label study to determine the safety and clinical benefit of TCR-redirected T cell therapy in patient with HBV related HCC post hepatectomy or radiofrequency ablation.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: TCR redirected T cells

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100039
      • Recruiting
      • Beijing 302 Hospital of China
      • Contact: Fusheng Wang, MD; Phone Number: 01066933328; Email: fswang302@163.com
      • Principal Investigator: Fusheng Wang, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Expression of the specific human leukocyte antigen (HLA) class I profile
2. Hepatocellular carcinoma (HCC) with positive test for hepatitis B virus surface antigen (HBsAg)
3. BCLC stage C
4. At least 1 month after surgical intervention or 2 weeks after TACE (may include other type of resection/ablation) No major post-operative complication

5. Laboratory criteria:

   1. Liver function: Child A, ALT < 200 U/L, AST < 200 U/L, Tbil < 17.1umol/L
   2. Renal Function: Creatinine clearance ≥ 60ml/minute
   3. Cardiac Function: No abnormality in cardiac enzyme and ECG
   4. Pulmonary Function (Lung): No abnormality in chest X-ray
6. Sexually active subjects must be willing to use an acceptable method of contraception
7. Willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures

Exclusion Criteria:

1. Subject experiencing acute infection or gastric bleeding within 30 days
2. Mid to late stage cirrhosis, i.e. Child-Pugh Score ≥ 7
3. Known history of testing positive for human immunodeficiency virus (HIV)
4. Other liver complications, including alcoholic liver disease, non-alcoholic autoimmune liver disease, drug induced liver disease
5. Serious systemic conditions, such as mental illness, cerebrovascular disease, coronary heart disease, diabetes, epilepsy
6. Women who are pregnant or breast-feeding
7. History of allergic reaction to blood products or investigational products
8. History of chronic alcoholism or drug abuse/addiction
9. Require systemic medications, such as steroids during the period of study drug administration
10. Exposure to any cell therapy such as, but not limited to NK, CIK, DC, CTL, stem cells therapy 6 months prior to study drug administration
11. Use of any investigational product (IP) or investigational medical device
12. Any condition which could jeopardize the safety of the patient and his/her compliance in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: TCR-Redirected T Cells; HBV antigen specific TCR redirected T cells	Biological: TCR redirected T cells; HBV antigen specific TCR redirected T cell Infusions. Subjects will receive 1x10^4 - 5x10^6 TCR redirected T cells by IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety evaluation based in Incidences of adverse events/serious adverse events	Review the safety profile of T-Cell Therapy by assessing adverse/serious adverse events reported.	Up to 1 month after the last infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate	Tumour assessment will be according to mRECIST v1.1. This is based on percentage of participants with Complete Response (CR) and Partial Response (PR) according to mRECIST v1.1 from baseline.	Start of Treatment until first documented CR or PR, assessed up to 56 treatment weeks (protocol-defined treatment duration is until disease progression, death, or loss to follow up, whichever came first)
Overall survival rate	Overall Survival (OS) defined as the time from randomisation until death by any cause. Participants will be followed up for survival follow up for at least five years.	Up to 5 years from the last infusion

Collaborators and Investigators

• Sponsor: Beijing 302 Hospital
• Collaborators: Lion TCR Pte. Ltd.
• Investigators: Principal Investigator: Fusheng Wang, MD, Beijing 302 Hospital of China

Publications and helpful links

General Publications

• Meng F, Zhao J, Tan AT, Hu W, Wang SY, Jin J, Wu J, Li Y, Shi L, Fu JL, Yu S, Shen Y, Liu L, Luan J, Shi M, Xie Y, Zhou CB, Wong RW, Lu-En W, Koh S, Bertoletti A, Wang T, Zhang JY, Wang FS. Immunotherapy of HBV-related advanced hepatocellular carcinoma with short-term HBV-specific TCR expressed T cells: results of dose escalation, phase I trial. Hepatol Int. 2021 Dec;15(6):1402-1412. doi: 10.1007/s12072-021-10250-2. Epub 2021 Nov 30.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): April 20, 2019
• Primary Completion (ANTICIPATED): June 1, 2022
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: April 1, 2019
• First Posted (ACTUAL): April 2, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 10, 2019
• Last Update Submitted That Met QC Criteria: April 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• 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: LTCR-HCC-3-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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