Redirected HBV-Specific T Cells in Patients With HBV-related HCC (SAFE-T-HBV)

• Status: Not yet recruiting
• Trial end date: 2022-12-31
• Target enrollment: 0
• Participant gender: All

Summary

This is a single center. single arm, open-label study to determine the safety of mRNA modified HBV-TCR redirected T-cells and to analyze the changes in tumor microenvironment caused by these HBV-TCR redirected T-cells in subjects with HBV-related HCC who are not amenable to/failed conventional treatment.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lion TCR Pte. Ltd.

Criteria

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

2. Presence of primary hepatocellular carcinoma in the liver with presence of measurable tumour by RECIST 1.1 criteria, that is not amenable to, or failed, conventional treatment options

3. Detectable HBV DNA integrations in the HCC tumour biopsy

4. Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points)

5. HLA class 1 profile matching HLA-class I restriction element of the available T cell receptors (restricted by HLA-A0201, HLA-B5801, HLA-Cw0801)

6. Life expectancy of at least 3 months

7. Serum anti HBV core antibody positive (at any historical time)

8. Adequate organ function as defined below: a. Differential white blood counts within normal reference ranges b. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 150 IU/ml c. Total conjugated serum bilirubin ≤ upper limit normal (ULN) d. eGFR ≥ 60ml/minute e. Hemoglobin > 10.0 mg/ dl f. Platelet count ≥ 100,000/ μl

9. 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

10. Willing to undergo biopsy of non-tumour and tumour liver tissue before and after treatment

11. Sexually active subjects must be willing to use an acceptable method of contraception such as double barrier contraception during treatment and for 28 days after the last dose of study drug

12. Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy

13. Willing and able to comply with all study procedures

Exclusion Criteria:

1. Brain metastasis

2. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment

3. Use of checkpoint inhibitors within 6 months of baseline liver biopsy procedure

4. Alterations of concomitant medications within 3 months of baseline liver biopsy procedure.

5. Likelihood to require any immunosuppressive treatments during the period of the clinical trial.

6. Patient's last RFA/TACE, or Y90 therapy is less than 3 and 6 months ago, respectively.

7. Decompensated cirrhosis Child-Pugh B or C (7 - 15 points)

8. Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy.

9. Use of any investigational product (IP) or investigational medical device within 30 days of study drug administration

10. Poorly controlled medical illness that in the opinion of the investigator would compromise the patient's ability to tolerate therapy

11. Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic pressure >110 mmHg, despite optimal medical management

12. Serum HBV DNA levels ≥ 200 IU/ml at screening

13. Serum HBsAg levels ≥ 10,000 IU/ml at screening

14. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples

15. Substance abuse, medical, psychological, or social conditions that may interfere with the subject's participation in the study or evaluation of study results.

16. Any condition or active infections which, in the investigator's opinion, makes the subject unsuitable for trial participation

17. Women who are pregnant or breast-feeding