A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Adaptimmune
- 入组人数
- 28
- 试验地点
- 19
- 主要终点
- Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)
研究概览
简要总结
This first time in human study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for HLA-A*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells.
When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.
Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years. Subjects who have a confirmed response or clinical benefit ≥4 weeks after the first T-cell infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the Interventional Phase of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
- •Subject has received at least one line of prior therapy
- •Subjects with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (progressive disease or unacceptable toxicity) at least one prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively. Subject may have received PD-1 or PDL-1 inhibitors and or chemotherapy. There is no limit on lines of prior anti-cancer therapy (a washout period applies for recent anti-cancer treatments).
- •Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
- •Subject is HLA-A*02:01 or HLA-A*02:06 positive.
- •Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming MAGE-A10 expression.
- •Subject has an ECOG Performance Status 0-1 and anticipated life expectancy >6 months prior to apheresis and >3 months prior to lymphodepletion.
- •Subject is ≥18 to ≤75 years of age
- •Adequate organ function
排除标准
- •Subject is HLA-A*02:05, HLA-B*15:01 and/or HLA-B*46:01 positive.
- •History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
- •Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
- •Active malignancy besides NSCLC within 3 years prior to screening.
- •Uncontrolled intercurrent illness including, but not limited to:
- •Ongoing or active infection;
- •Clinically significant cardiac disease
- •Inadequate pulmonary function
- •Interstitial lung disease
研究组 & 干预措施
Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T
干预措施: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T (Biological)
结局指标
主要结局
Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE)
时间窗: 24 months
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; cardiac and pulmonary assessments, including ECG and troponin.
次要结局
- Interval between the date of first T cell infusion and date of disease progression or death due to any cause(24 months)
- Best Overall Response (BOR)(24 months)
- Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause(24 months)
- Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR)(24 months)
- Interval between the date of first documented evidence of SD until first documented disease progression or death due to any cause(24 months)
- Interval between the date of first T cell infusion dose and first documented evidence of CR or PR(24 months)
- To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion.(15 years)
- Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause(24 months)