NCT06196658尚未招募早期 1 期
Early Phase I Study of Autologous T Cells Engineered to Express Anti-EX02 Chimeric Antigen Receptor (EX02 CAR-T) for Unresectable Pancreatic/Bile Duct Cancer
Zhang Xiaofeng,MD0 个研究点目标入组 6 人开始时间: 2024年1月1日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 6
- 主要终点
- Objective Response Rate
研究概览
简要总结
This is a early Phase 1 open-label study to explore the safety and possible efficacy of EX02 CAR T cell therapy in the treatment of patients with unresectable and/or metastatic pancreatic/bile duct cancer.
Each participant will undergo leukapheresis after enrolment, receive treatment of the conditioning chemotherapy of cyclophosphamide and fludarabine, and an intra-tumoral injection or intraperitoneal infusion of Ex02 CAR T cells, probably followed by an intravenous infusion of EX02 CAR T cells.
Each participant will proceed through the following study procedures:
- Screening
- Enrollment/Leukapheresis
- Conditioning chemotherapy
- CAR T treatment
- Post-treatment assessment
- Long-term follow-up
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer 2) Ineligible for, refractory to or relapsed after first or second line of chemotherapy 3) Presence of at least one measurable target lesion according to RECIST v1.1 4) EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells) 5) Male or female, ≥18 years 6) ECOG performance status 0 to 1 7) Expected life expectancy >3 months 8) Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential 9) Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
- •Neutrophil count ≥ 1.5×10^9/L
- •Hemoglobin ≥ 90g/L
- •Platelet count ≥ 100×10^9/L
- •Lymphocyte count ≥ 0.5×10^9/L 10) Adequate liver, kidney, heart and lung functions at least indicated by:
- •Creatinine clearance ≥ 60ml/min
- •ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved)
- •LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam
- •No or only small amount of pleural fluid or ascites; blood oxygen saturation ≥ 95% 11) Voluntary participation in the trial and signing informed consent form
排除标准
- •28 participants fulfilling the following criteria will be enrolled.
- •Inclusion criteria:
- •Must have a confirmed diagnosis of unresectable or metastatic pancreatic cancer or bile duct cancer
- •Ineligible for, refractory to or relapsed after first or second line of chemotherapy
- •Presence of at least one measurable target lesion according to RECIST v1.1
- •EX02 positive tumor cell membrane (as shown in IHC staining of tumor specimen or in flow cytometry of ascites cells)
- •Male or female, ≥18 years
- •ECOG performance status 0 to 1
- •Expected life expectancy >3 months
- •Negative pregnancy test at screening and prior to initiating lymphodepletion chemotherapy or study drug administration, and willingness to practice birth control for woman with childbearing potential
- •Adequate hematology function indicated by followings (without blood transfusion or administration with growth factors in last four weeks):
- •Neutrophil count ≥ 1.5×10^9/L
- •Hemoglobin ≥ 90g/L
- •Platelet count ≥ 100×10^9/L
- •Lymphocyte count ≥ 0.5×10^9/L
- •Adequate liver, kidney, heart and lung functions at least indicated by:
- •Creatinine clearance ≥ 60ml/min
- •ALT and AST ≤ 2.5 ULN (≤ 5 ULN when liver is involved)
- •LVEF ≥ 50%; absence of pericardial fluid; no significant abnormality in ECG exam
- •No or only small amount of pleural fluid or ascites; blood oxygen saturation ≥ 95%
- •Voluntary participation in the trial and signing informed consent form
- •Exclusion criteria:
- •Active viral infection including but not limiting hepatitis A, hepatitis B, hepatitis C or HIV
- •History of acquired immunodeficiency syndrome (AIDS)
- •Is pregnant or lactating
- •Unwilling to practice birth control
- •Planned intraperitoneal chemotherapy (such as HIPEC) within 28 days
- •Received systemic immune inhibitors or corticosteroids (prednisone 15mg/day or above equivalent dose) within 2 weeks of the time of initiating conditioning chemotherapy
- •Current involvement of:
- •Active infection which requires treatment with systemic administration
- •Active coagulation disorders or receiving anti-coagulant treatment (except for aspirin)
- •Active hemolytic anemia
- •Significant arrhythmia, or history of myocardial infarction, ventricular tachycardia, or ventricular fibrillation
- •Active obstructive or constrictive lung disease
- •Active autoimmune disease such as rheumatoid arthritis or immunodeficiency disease
- •Active CNS metastases or cerebrospinal malignancy
- •Uncontrolled diseases including disorders of cardiovascular, respiratory, renal, gastrointestinal, urogenital or immune systems
- •Active second malignancy in addition to the studied one, excluding low-risk neoplasms such as non-metastatic basal cell or squamous cell skin carcinoma
- •History of hypersensitivity to any drugs planning to be used in this study
- •History of treatment with any genetically modified T cell therapy (including CAR T cells and TCR T cells)
- •Any conditions that investigator consider as ineligibility of participation
研究组 & 干预措施
anti-EX02 CAR T cells
Experimental
干预措施: anti-EX02 CAR T cells (Drug)
结局指标
主要结局
Objective Response Rate
时间窗: 24 weeks
Objective Response Rate (ORR) is the proportion of participants with an objective response (either a complete response \[CR\] or partial response \[PR\]) in participants who received at least 1 dose of EX02CART and at least the 6-week tumor evaluation as determined by the investigator according to RECIST v1.1.
Frequency and severity of treatment-related adverse events (TEAEs)
时间窗: 4 weeks after the first CAR-T cell infusion
Grade and type of toxicity per dose level; fraction of patients who experience toxicity (including allergic reactions to T cell infusions) of ≥ Grade 3 according to CTCAEv5.0, cytokine release syndrome (CRS) of ≥ Grade 3 according to ASTCT consensus and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).
次要结局
- Duration of Response (DOR)(24 weeks)
- Progression Free Survival (PFS)(24 weeks)
- Disease control rate (DOC)(24 weeks)
- 5) Volume of ascites measured by ultrasonography and/or frequency and volume of ascites aspiration(24 weeks)
- Overall survival (OS)(24 weeks)
研究者
Zhang Xiaofeng,MD
chief physician
First People's Hospital of Hangzhou
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