Phase 1 Dose Escalation, Multi-tumor Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered MAGE-A4ᶜ¹º³²T in HLA-A2+ Subjects With MAGE-A4 Positive Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- USWM CT, LLC
- 入组人数
- 71
- 试验地点
- 22
- 主要终点
- Measurement of RCL in genetically modified T cells.
研究概览
简要总结
This study will investigate the safety and tolerability of MAGE-A4ᶜ¹º³²T cell therapy in subjects who have the appropriate HLA-A2 tissue marker and whose urinary bladder, melanoma, head and neck, ovarian, non-small cell lung, esophageal, gastric, synovial sarcoma, or myxoid/round call liposarcoma (MRCLS) tumor has the MAGE-A4 protein expressed. This study will take a subject's T cells and give them a T cell receptor protein that recognizes and attacks the tumors. This study has a substudy component that will investigate the safety and tolerability of MAGE-A4c1032T cell therapy in combination with low dose radiation in up to 10 subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Subject is ≥18 to 75 years of age at the time of signing the study informed consent.
- •Subject has histologically confirmed diagnosis of any one of the indicated tumor types
- •Subject is HLA-A*02 positive. (This determination will be made under screening protocol ADP-0000-001).
- •Subject's tumor shows expression of the MAGE-A4 RNA or protein. (This determination will be made under screening protocol ADP-0000-001).
- •Adequate organ function as indicated in the study protocol
- •Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion
- •Subject meets disease-specific requirements per protocol
- •7. Subject has anticipated life expectancy > 6 months prior to leukapheresis and >3 months prior to lymphodepletion.
排除标准
- •Subject does not express appropriate HLA-A genotype
- •Subject is receiving excluded therapy/treatment per protocol
- •Subject has symptomatic CNS metastases.
- •Subject has any other active malignancy besides the tumor under study within 3 years prior to Screening. Subject has uncontrolled intercurrent illness.
- •Subject has active infection with HIV, HBV, HCV or HTLV
- •Subject is pregnant or breastfeeding.
- •Additional Exclusion Criteria for the Radiation Substudy:
- •Subject does not meet eligibility criteria for the main study (ADP-0044-001).
- •Subject does not have at least one target lesion amenable to radiation.
- •Certain radiation therapy within 6 months of clinical trial are an exclusion.
- •Metastatic disease impinging on the spinal cord or threatening spinal cord compression.
研究组 & 干预措施
Autologous genetically modified MAGE-A4ᶜ¹º³²T cells
干预措施: Autologous genetically modified MAGE-A4ᶜ¹º³²T cells (Genetic)
Radiation Sub-Study: Autologous genetically modified MAGE-A4c1
干预措施: Autologous genetically modified MAGE-A4c1032T cells combined with low dose radiation (Radiation)
结局指标
主要结局
Measurement of RCL in genetically modified T cells.
时间窗: 3.5 years
Evaluation of RCL in subject PBMCs using PCR-based assay.
Number of subjects with adverse events (AE), including serious adverse events (SAEs).
时间窗: 3.5 years
Determine if treatment with autologous genetically modified T cells (MAGE-A4ᶜ¹º³²T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.
Evaluation of persistence of genetically modified T cells.
时间窗: 3.5 years
Evaluation of persistence of genetically modified T cells in the periphery.
Determining dose limiting toxicities (DLT) and optimally tolerated dose range
时间窗: 3.5 years
Evaluate DLTs and toxicity assessment using NCI CTCAE.
次要结局
- Interval between the date of first documented evidence of stable disease (SD) until first documented disease progression or death due to any cause.(3.5 years)
- Interval between the date of first T cell infusion and date of death due to any cause.(3.5 years)
- Interval between the date of first T cell infusion dose and first documented evidence of CR or PR.(3.5 years)
- Proportion of subjects with a confirmed Complete Response (CR) and/or Partial Response (PR).(3.5 years)
- Number and % of subjects having any Long Term Follow Up Adverse Events (AEs)(15 years post last treatment (infusion))
- Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause.(3.5 years)
- Interval between the date of first T cell infusion and the earliest date of disease, progression or death due to any cause(3.5 years)