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

NCT05195294 — Phase 2, Not yet recruiting, 55 participants, Lion TCR Pte. Ltd.

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A Multi-center, Phase 2 Study for Autologous T Cells Transfected With mRNA Encoding HBV Antigen-specific TCR (LioCyx-M) as Monotherapy or as Combination With Lenvatinib for Advanced HBV-related Hepatocellular Carcinoma

Registry	NCT05195294
Status	Not yet recruiting
Phase	Phase 2
Study type	Interventional; non randomized, sequential, masking: none, treatment
Enrollment	55 (Estimated)
Sponsor	Lion TCR Pte. Ltd. (Industry)
Conditions	Hepatocellular Carcinoma, Liver Cancer, Adult, Liver Cell Carcinoma
Interventions	LioCyx-M, Lenvatinib (Biological, drug)
Dates	start 2025-03-01 (estimated), primary completion 2026-12-01 (estimated), completion 2028-12-01 (estimated), first posted 2022-01-18, last updated 2025-03-10

-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).

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+Arms and interventions

Arm	Type	Interventions	Description
LioCyx-M monotherapy	Experimental	Biological: 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	Experimental	Biological: LioCyx-M; Drug: Lenvatinib	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 (Biological): HBV antigen specific TCR redirected T cells
Lenvatinib (Drug): 12 mg once daily for patients ≥60 kg, 8 mg for patients <60kg by oral

+Outcome measures

Primary outcomes

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 outcomes

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

+Eligibility

Sex: All, ages: 18 Years to 75 Years

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