A Phase 1/2 Single Arm Open-Label Clinical Trial of Gavocabtagene Autoleucel (Gavo-cel) in Patients With Advanced Mesothelin-Expressing Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 57
- 试验地点
- 11
- 主要终点
- Phase 1- Primary Objective
研究概览
简要总结
Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex.
This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient is at least 18 years of age at the time the Informed Consent is signed.
- •Patient has a pathologically confirmed diagnosis of either Malignant Pleural/Peritoneal Mesothelioma (MPM), Serous Ovarian Adenocarcinoma, Cholangiocarcinoma, or Non-Small Cell Lung Cancer (NSCLC) at screening.
- •Patient's tumor has been pathologically reviewed by the central laboratory. For Serous Ovarian Adenocarcinoma, patients must have confirmed positive MSLN expression on >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by immunohistochemistry (IHC). Ovarian patients will subsequently be stratified into two groups: high MSLN expression (>/= 50% of tumor cells that are 2+ and/or 3+) or low MSLN expression (>/= 30% of tumor cells that are 1+, 2+, and/or 3+ not meeting criteria for the high MSLN expression group). MPM patients must have MSLN expression of >/= 50% of tumor cells that are 2+ and/or 3+ by IHC. Cholangiocarcinoma and NSCLC patients must have MSLN expression of >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by IHC.
- •Prior to gavo-cel infusion, patients must have received at least 1 systemic standard of care therapy for metastatic or unresectable disease, with the exception of Cholangiocarcinoma patients who may have elected not to pursue standard frontline therapy. Regardless of tumor type, patients must not exceed 5 prior lines of therapy (excluding bridging therapy and surgical procedures). More details provided in the clinical protocol.
- •Patient has an Eastern Cooperative Oncology Group performance status 0 or
- •Patient has a left ventricular ejection fraction > 45% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
- •Patient is fit for leukapheresis and has adequate venous access for the cell collection.
- •Patient must have adequate organ function as indicated by the laboratory values in the clinical protocol
排除标准
- 未提供
研究组 & 干预措施
Lymphodepletion followed by gavo-cel
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel
干预措施: gavo-cel (Biological)
Lymphodepletion followed by gavo-cel
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel
干预措施: fludarabine (Drug)
Lymphodepletion followed by gavo-cel
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel
干预措施: cyclophosphamide (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel
干预措施: gavo-cel (Biological)
Lymphodepletion followed by gavo-cel plus nivolumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel
干预措施: fludarabine (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel
干预措施: cyclophosphamide (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel
干预措施: Nivolumab (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
干预措施: gavo-cel (Biological)
Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
干预措施: fludarabine (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
干预措施: cyclophosphamide (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
干预措施: Nivolumab (Drug)
Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab
fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Phase 1- Primary Objective
时间窗: DLTs within 28 days post-treatment
Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.
Phase 2- Primary Objective
时间窗: ORR at 3 months; DCR based on ORR + SD lasting at least 8 weeks
To evaluate the efficacy of autologous genetically modified T cells (gavo-cel), with or without immuno-oncology agents, in patients with MSLN-expressing unresectable, metastatic, or recurrent cancers as determined by overall response rate and disease control rate using RECIST v1.1 (or mesothelioma-specific RECIST criteria, if applicable).
次要结局
未报告次要终点