Phase I Clinical Study on Safety and Feasibility of DLL3 Targeted α-PD-L1/4-1BB Modifying Chimeric Antigen Receptor T-cells in Patients With Relapsed or Refractory Small Cell Lung Cancer (SCLC)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Dose-limiting toxicity (DLT)
研究概览
简要总结
A study to evaluate the safety and feasibility of α-PD-L1/4-1BB DLL3 Chimeric Antigen Receptor (CAR)-T (BHP01) in patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC) and determine the appropriate CAR-T cell dose. Next, In dose expansion phase, patients were assign two groups with/without bridge radiotherapy.
详细描述
Small cell lung cancer (SCLC) accounts for about 15% of lung cancers, and two-thirds of cases are metastatic at the time of diagnosis. The inhibitory notch ligand delta-like ligand 3 (DLL3) is aberrantly expressed on the surface of up to 85% of SCLC cells and minimally expressed in normal tissues, making it a compelling therapeutic target. This is a phase I, first-in-human, 3+3 dose escalation study to evaluate the safety and feasibility of BHP01 in patents with relapsed/refractory SCLC who progressed after at least 1 platinum based chemotherapy regimen.This is a dose escalation and dose expansion study. 12-21 patients with relapsed/refractory SCLC are planned to be enrolled (Group Pre-A/A/B/C). After the Dose-limiting toxicity (DLT) observation period of the related dose group finished.16 patients are planned to enroll in dose expansion phase who was assign two groups with/without bridge radiotherapy.
研究设计
- 研究类型
- 干预性
- 分配方式
- 不适用
- 干预模型
- 单组
- 主要目的
- 治疗
- 盲法
- 开放（无盲法）
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
- Patients with recurrent or refractory small cell lung cancer (SCLC) confirmed by histology or cytology who have relapsed or progressed after treatment with one previous platinum-based regimen;
- Patients can provide sufficient tumor tissue (fresh or paraffin sections, etc.);
- Age 18 ~70 (including boundary), for both men and women;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
- Life expectancy ≥3 months;
- At least one extracranial measurable lesion (RECIST v1.1) exists；for lesion after radiotherapy， must be confirmed that the lesion has progressed ;
- Patients in limited-stage at the initial diagnosis must undergo radical thoracic radiotherapy and the time of tumor progression is not less than 1 months from the end of radiotherapy, or radical thoracic dose radiotherapy cannot be performed for specific reasons; The time elapsed since the completion of radiotherapy for brain metastases shall be no less than 1 months；
- The test results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C and syphilis were negative at screening (If hepatitis B core antibody (HBcAb) is positive, additional HBV DNA testing is required, and subjects whose test result is less than the reference value can be included in the study) ;
- Female patients or male reproductive age patients and their partners should agree to effective contraception from sighing Informed Consent Form (ICF) to 6 months after the last BHP01 infusion.
排除标准
- Patients with known primary Central Nervous System (CNS) tumor, or meningeal metastasis, or patients with unstable CNS metastasis (symptomatic, requiring hormonal therapy within 4 weeks before investigational treatment, or no radiographic evidence of stabilization of the lesion for more than 4 weeks);
- Received major surgical procedures （except for diagnosis） within 4 weeks before PBMCs collection, or are expected to require major surgical procedures during the study;
- Received Chinese herbal medicine or Chinese patent medicine for anti-tumor indications within 7 days before Peripheral Blood Mononuclear Cells (PBMCs) collection;
- Patients with a history of idiopathic pulmonary fibrosis, mechanical pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia or idiopathic pneumonia, or evidence of active pneumonia by chest computer tomography (CT) at screening [a history of radiation pneumonia (fibrosis) in the irradiated field may participate in this study];
- Poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage procedures (once a month or more frequently);
- Poorly controlled or symptomatic hypercalcemia (ionic calcium> 1.5 mmol/L, calcium> 12 mg/dL or corrected calcium> ULN);
- Presence of active or previous autoimmune diseases or immunodeficiencies, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, etc.;
- Severe infection within 4 weeks before the start of PBMCs collection, including but not limited to hospitalization due to infection, bacteremia, severe pneumonia, or any active infection that may affect the patient's safety;
- Serious cardiovascular and cerebrovascular diseases (such as heart disease ≥New York Heart Association class II, myocardial infarction or cerebrovascular accident), unstable arrhythmia or unstable angina pectoris within 3 months before PBMCs collection;
- Previous treatment with DLL 3 target drugs or CAR-T or other gene-modified T cells;
- Received any other Investigational drug within 28 days prior to PBMCs collection;
- A history of mental illness;
- Incapacitated persons or persons with limited capacity;
- pregnant or lactating females; Males or females who are unwilling to use adequate contraception; Females of childbearing potential are required to undergo a pregnancy study during the screening period;
研究组 & 干预措施
α-PD-L1/4-1BB DLL3 CAR-T (BHP01) Treatment
The Patients enrolled will be sequentially assigned to the corresponding dose level, BHP01 was administered intravenous infusion at different cell dose levels. The patients were received multiple-dose infusion according to investigator's evaluation.
干预措施: α-PD-L1/4-1BB DLL3 CAR-T (BHP01) (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT)
时间窗: day1-day28
Safety
次要结局
- Objective Response Rate (ORR)(up to 1 year after the enrollment)
- Progression-free survival (PFS)(up to 1 year after the enrollment)
- Disease control rate (DCR)(up to 1 year after the enrollment)
- Duration of response (DOR)(up to 1 year after the enrollment)
- CAR-T cell numbers(up to 1 year after the enrollment)
- Overall-Survival (OS)(up to 1 year after the enrollment)
研究者
You Lu
Chair of Department of Thoracic Cancer
Sichuan University
研究点 (1)
标识符
- NCT 编号
- NCT06348797
- 其他研究编号
- BHP01-01
日期
- 首次提交
- (2年前)
- 首次发布
- (2年前)
- 主要完成日期
- (3个月后)
- 研究完成日期
- (3个月后)
- 最近核实
- (3个月前)
- 最近更新
- (2个月前)
监管与共享
- FDA 监管药物
- 否
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 否
- 是否有结果
- 否