Study of HBV-TCR T Cells (LioCyx-M) as Monotherapy or as Combination With Lenvatinib for HBV-related HCC

Phase 2

Not yet recruiting

• Conditions: Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Cell Carcinoma
• Interventions: Biological: LioCyx-M; Drug: Lenvatinib

• Registration Number: NCT05195294
• Lead Sponsor: Lion TCR Pte. Ltd.

Brief Summary

This is an open-label and multi-center Phase 2 study to evaluate the safety and efficacy of autologous T-cells transfected with mRNA encoding Hepatitis-B virus (HBV)-antigen-specific T cell receptor (TCR) (LioCyx-M) as monotherapy or as combination with lenvatinib for the treatment of advanced HBV-related hepatocellular carcinoma (HCC).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-03
• Study First Submitted QC: 2022-01-04
• Study First Posted: 2022-01-18
• Status Verified: 2025-01
• Study Start: 2025-03
• Last Update Submitted: 2025-03-05
• Last Update Posted: 2025-03-10
• Primary Completion: 2026-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

1. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
2. Advanced HCC with diagnosis confirmed by histology/ cytology or clinically by AASLD criteria in cirrhotic patients.
3. Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies
4. Patients who failed first-line systemic therapy for HCC
5. Serum HBsAg positivity
6. Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points)
7. HLA class 1 profile matching HLA-class I restriction element of the available T cell receptor

Exclusion Criteria

1. Brain metastasis
2. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment, except for in situ carcinoma of the cervix, non-melanoma skin carcinoma localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer and superficial bladder tumours.
3. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples
4. History of severe allergic anaphylactic reactions to T cell therapy products and/or lenvatinib
5. Local or loco-regional therapy of intrahepatic tumour lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ≥4 weeks before the first infusion of LioCyx-M.
6. Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, tyrosine kinase inhibitor therapy, and immunotherapy.
7. Treatment with anticancer therapy, including investigational therapy, within 2 weeks prior to first infusion. For prior therapies with a half-life longer than 3 days, discontinuation of the therapy must have occurred at least 28 days prior to leukapheresis.
8. Treatment with other investigational therapy within 28 days prior to initiation of study treatment. Patients participating in surveys or observational studies are eligible to participate in this study.
9. Likelihood to require any immunosuppressive treatments during the period of the clinical trial (Localized steroid use should be allowed)
10. Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except for HBV)
11. Significant cardiovascular disease (such as New York Heart Association (NYHA) Functional Classification Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable angina
12. Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic pressure >110 mmHg, despite optimal medical management

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LioCyx-M monotherapy	LioCyx-M	Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M).
LioCyx-M + lenvatinib combinational therapy	LioCyx-M	Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M) with daily intake of lenvatinib.
LioCyx-M + lenvatinib combinational therapy	Lenvatinib	Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M) with daily intake of lenvatinib.

Primary Outcome Measures

Name	Time	Method
Assessments of adverse events/serious adverse events	Up to 4 years from study treatment initiation	To evaluate the safety of LioCyx-M as a monotherapy and in combination with lenvatinib
Objective response rate (ORR)	Up to 4 years from study treatment initiation	To evaluate the anti-tumor efficacy of LioCyx-M as a monotherapy and in combination with lenvatinib

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	Up to 4 years from study treatment initiation	To evaluate the anti-tumor efficacy of LioCyx-M as a monotherapy and in combination with lenvatinib
Time to radiographic progression (TTRP)	Up to 4 years from study treatment initiation	To evaluate the anti-tumor efficacy of LioCyx-M as a monotherapy and in combination with lenvatinib
Duration of response (DoR)	Up to 4 years from study treatment initiation	To evaluate the anti-tumor efficacy of LioCyx-M as a monotherapy and in combination with lenvatinib
Overall survival (OS)	Up to 4 years from study treatment initiation	To evaluate the anti-tumor efficacy of LioCyx-M as a monotherapy and in combination with lenvatinib