NCT03680560终止1 期
A Phase 1 Study of an Autologous ACTR T Cell Product in Combination With Trastuzumab, a Monoclonal Antibody, in Subjects With HER2-Positive Advanced Malignancies
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 6
- 主要终点
- Determination of recommended phase 2 dose (RP2D) regimen
研究概览
简要总结
This is a Phase 1, open-label, multi-center study to assess safety and determine the recommended phase 2 dose (RP2D) of ACTR T cell product (ACTR707 or ACTR087) in combination with trastuzumab, following lymphodepleting chemotherapy in subjects with HER2-positive advanced malignancies.
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
- •Signed written informed consent obtained prior to study procedures
- •Histologically-confirmed Her2 positive advanced solid tumor malignancy with documented disease progression during or immediately following the immediate prior therapy, or within 6 months of completing adjuvant therapy for subjects with breast cancer
- •Subjects must have previously received adequate standard therapy for treatment of their malignancy
- •For those with metastatic breast cancer, must have received HER2-directed therapy including trastuzumab, pertuzumab and ado-trastuzumab in any breast cancer disease setting
- •For those with advanced gastric cancer, adequate prior treatment with HER2-directed chemotherapy is required
- •At least 1 measurable lesion by iRECIST
- •Able to provide fresh tumor biopsy or archived block specimen taken since time of most recent anti-HER2 mAb-directed therapy
- •ECOG of 0 or 1
- •Life expectancy ≥ 6 months
- •LVEF ≥ 50% by MUGA or ECHO
- •Absolute neutrophil (ANC) count ≥ 1500/ µL
- •Platelet count ≥ 100,000/µL
- •Hemoglobin ≥ 9g/dL
- •Estimated GFR >30mL/min/1.73m2
排除标准
- •glioblastoma multiforme or other primary CNS tumors are excluded
- •clinically significant cardiac disease
- •clinically significant active infection
- •clinical history, prior diagnosis, or overt evidence of autoimmune disease
- •current use of more than 5mg/day of prednisone (or an equivalent glucocorticoid)
- •Prior treatment as follows:
- •prior cumulative doxorubicin dose greater than or equal to 300 mg/m^2 or equivalent
- •chemotherapy within 2 weeks of enrollment
- •external beam radiation within 2 weeks of enrollment (28 days if CNS-directed therapy)
- •any monoclonal antibody (mAb) or other protein therapeutic containing Fc-domains within 4 weeks of enrollment
- •pertuzumab within 4 months of enrollment
- •Experimental agents within 3 half-lives or 28 days prior to enrollment, whichever is shorter
- •allogeneic hematopoietic stem cell transplant (HSCT)
- •prior infusion of a genetically modified therapy
- •Pregnant or breastfeeding
研究组 & 干预措施
ACTR T cell product in combination with trastuzumab
Experimental
干预措施: ACTR T Cell Product (Biological)
ACTR T cell product in combination with trastuzumab
Experimental
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Determination of recommended phase 2 dose (RP2D) regimen
时间窗: 42 days
Review of DLTs, maximum tolerated dose (MTD), incidence and severity of AEs and clinically significant abnormalities of laboratory values
Safety and tolerability of ACTR T cell product with trastuzumab as assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of adverse events (AEs) and clinically significant abnormalities of laboratory values
时间窗: 42 days
次要结局
- Anti-tumor activity as measured by overall response rate (ORR) per iRECIST(52 weeks)
- Anti-tumor activity as measured best overall response (BOR)(52 weeks)
- Anti-tumor activity as measured by duration of response (DOR)(52 weeks)
- Anti-tumor activity as measured by progression-free survival (PFS)(52 weeks)
- Anti-tumor activity as measured by overall survival (OS)(52 weeks)
- Assessment of persistence of ACTR as measured by flow cytometry(52 weeks)
- Assessment of persistence of ACTR as measured by quantitative polymerase chain reaction (qPCR)(52 weeks)
- Assessment of ACTR phenotype and function as measured by flow cytometry(52 weeks)
- Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR T cell product administration(52 weeks)
- Trastuzumab pharmacokinetics (PK)(52 weeks)
研究者
研究点 (6)
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