An Open-Label, Dose-Escalation Phase I Clinical Study of T Cell Receptor Gene-Engineered and Dominant Negative TGF-β Receptor T Cell Therapy Targeting KRAS Mutations in the Treatment of Subjects With Advanced Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
An open label, dose-escalation clinical study to evaluate the safety, anti-tumor activity and pharmacokinetics/pharmacodynamic (PK/PD) of NW-301VT in subjects with advanced solid tumor.
详细描述
Using a modified 3+3 dose escalation design, this study will enroll ~9 subjects to characterize the safety and preliminary anti-tumor activity of NW-301VT . Eligible subjects will undergo leukapheresis for autologous cell product manufacturing, and will receive a 3-day lymphodepleting regimen consisting of cyclophosphamide and fludarabine, followed by a single-dose intravenous infusion of NW-301VT. following this intervention, subjects will be monitored for safety and AE, and tumor evaluation will be performed at pre-specified timepoints per protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Age between 18-75 years
- •Diagnosis of pathologically or histologically confirmed unresectable or advanced solid tumor, and have no standard treatment options available or unable to tolerate the currently available standard treatments
- •HLA-A*11:01positive
- •Tumor has KRAS G12V mutation
- •Adequate organ function prior to apheresis and lymphodepleting chemotherapy
- •ECOG performance status of 0-1
- •At least one tumor lesion measurable according to RECIST 1.1
- •(Additional protocol-defined Inclusion criteria may apply.)
排除标准
- •Received the following treatments: Cytotoxic chemotherapy within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion; Treatment with antibodies (including but not limited to those with monoclonal antibodies and immune checkpoint inhibitors) or other biologic therapy within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion; Immunosuppressive agents (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutic agents, mycophenolate mofetil, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti-IL-6, or anti-IL-6 receptor) within 2 weeks prior to apheresis and within 1 week prior to lymphodepletion
- •History of allergic reactions to cyclophosphamide, fludarabine, or any other chemical or biological components of the drugs used in this study
- •History of chronic or recurrent severe autoimmune disease, or active immune disease requiring treatment with steroids or other immunosuppressive agents within 1 year prior to enrollment
- •Have symptomic CNS metastases
- •Have leptomeningeal disease or carcinomatous meningitis
- •Have ongoing or active infection
- •Active infections with HIV, HBV, HCV, CMV or syphilis
- •Breastfeeding or pregnant
- •(Additional protocol-defined Exclusion criteria may apply.)
研究组 & 干预措施
NW-301VT monotherapy in patients with Solid Tumors with KRAS G12V mutation
干预措施: NW-301VT (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: 28 days following NW-301VT infusion
Safety
次要结局
- Objective response rate (ORR)(Through study completion, an average of 2 years)
- Duration of response (DOR)(Through study completion, an average of 2 year)
研究者
TingBo Liang
Professor
Zhejiang University