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

NCT05195294 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: LTCR-HCC-3-4
• Study Type: interventional
• Target: 55
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Hepatocellular Carcinoma; Liver Cancer, Adult; Liver Cell Carcinoma

Keywords

TCR T cells; Hepatocellular Carcinoma; HBV; Hepatitis B virus

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Progression free survival (PFS)

  Up to 4 years from study treatment initiation

• Time to radiographic progression (TTRP)

  Up to 4 years from study treatment initiation

• Duration of response (DoR)

  Up to 4 years from study treatment initiation

• Overall survival (OS)

  Up to 4 years from study treatment initiation

Study Arms (2)

LioCyx-M monotherapy

EXPERIMENTAL

Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M).

Biological: LioCyx-M

LioCyx-M + lenvatinib combinational therapy

EXPERIMENTAL

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; Drug: Lenvatinib

Interventions

LioCyx-M BIOLOGICAL

HBV antigen specific TCR redirected T cells

LioCyx-M + lenvatinib combinational therapy; LioCyx-M monotherapy

Lenvatinib DRUG

12 mg once daily for patients ≥60 kg, 8 mg for patients \<60kg by oral

LioCyx-M + lenvatinib combinational therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lion TCR Pte. Ltd.: lead

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis B

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis

Central Study Contacts

Regina Wong

CONTACT

+65 68130738; regina.wong@liontcr.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2021
• First Posted: January 18, 2022
• Study Start: March 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 10, 2025

Record last verified: 2025-01