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

Study Overview
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Brief Summary
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This is a single arm, open-label and multi-center Phase 1b/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).

Official Title
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A Multi-center, Phase 1b/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

Conditions
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Hepatocellular Carcinoma, Liver Cancer, Adult, Liver Cell Carcinoma

Intervention / Treatment
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* Biological: LioCyx-M
* Drug: Lenvatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Advanced HCC with diagnosis confirmed by histology/ cytology or clinically by AASLD criteria in cirrhotic patients. Disease that is not amenable to curative surgical and/or locoregional therapies, or progressive disease after surgical and /or locoregional therapies Patients who failed first-line systemic therapy for HCC Serum HBsAg positivity Non-cirrhotic or compensated cirrhosis Child-Pugh A (5 - 6 points) HLA class 1 profile matching HLA-class I restriction element of the available T cell receptor Exclusion Criteria: Brain metastasis 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. Lack of peripheral venous or central venous access or any condition that would interfere with drug administration or collection of study samples History of severe allergic anaphylactic reactions to T cell therapy products and/or lenvatinib 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. Concurrent administration of any other anti-tumour therapy, including cytotoxic chemotherapy, tyrosine kinase inhibitor therapy, and immunotherapy. 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. 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. Likelihood to require any immunosuppressive treatments during the period of the clinical trial (Localized steroid use should be allowed) Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except for HBV) 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 Uncontrolled hypertension, defined as systolic blood pressure >160 mmHg or diastolic pressure >110 mmHg, despite optimal medical management

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LioCyx-M monotherapy<br>Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M). | Biological: LioCyx-M<br>* HBV antigen specific TCR redirected T cells<br>|
| Experimental: LioCyx-M + lenvatinib combinational therapy<br>Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M) with daily intake of lenvatinib. | Biological: LioCyx-M<br>* HBV antigen specific TCR redirected T cells<br>Drug: Lenvatinib<br>* 12 mg once daily for patients ≥60 kg, 8 mg for patients <60kg by oral<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TCR T cells, Hepatocellular Carcinoma, HBV, Hepatitis B virus