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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 55
- 主要终点
- Assessments of adverse events/serious adverse events
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
LioCyx-M monotherapy
Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M).
干预措施: LioCyx-M (Biological)
LioCyx-M + lenvatinib combinational therapy
Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M) with daily intake of lenvatinib.
干预措施: LioCyx-M (Biological)
LioCyx-M + lenvatinib combinational therapy
Patients will receive up to 8 biweekly infusions of HBV antigen specific TCR redirected T cells (LioCyx-M) with daily intake of lenvatinib.
干预措施: Lenvatinib (Drug)
结局指标
主要结局
Assessments of adverse events/serious adverse events
时间窗: 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)
时间窗: 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
次要结局
- 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)