A Phase II Trial of Adoptive Cell Therapy With Tumor-infiltrating Lymphocytes in Patients With Non-Small Cell Lung Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Progression-free rate at 6 months after Tumor-infiltrating lymphocytes transfer.
研究概览
简要总结
Aim of the study is to investigate the efficacy and safety of adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) in patients with advanced pre-treated non-small cell lung cancer (NSCLC).
详细描述
Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a personalized immunotherapy. TIL-ACT involves the infusion of autologous CD4+ and CD8+ T lymphocytes collected from tumor material and expanded ex-vivo with IL-2. These polyclonal immune cells can recognize and target multiple individualized tumor-specific antigens.
Clinical trials have demonstrated significant response rates in advanced melanoma patients. However, few trials have investigated TIL-ACT in other solid tumors, including NSCLC. For NSCLC patients experiencing disease progression after standard therapies (immune checkpoint inhibitors, targeted therapies), effective options are limited, often restricted to traditional chemotherapy with modest response rates, short durability, and significant toxicity. TIL-ACT represents an attractive individualized treatment approach for NSCLC patients.
The BaseTIL-02L study is a single-arm phase II trial investigating TIL-ACT efficacy in pretreated NSCLC patients. The study protocol includes preconditioning non-myeloablative chemotherapy (cyclophosphamide and fludarabine) and in-vivo TIL activation with high-dose interleukin 2 (for up to 15 doses, every 8 hours) following TIL transfer.
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
- •Ability of the patient to understand the purpose of the study, provide signed and dated informed consent prior to performing any protocol-related procedures (including screening evaluations), and be able and willing to comply with the study procedures.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 (cf. Appendix).
- •Histologically confirmed NSCLC.
- •Disease progression after at least one standard therapy and without any approved curative-intended treatment option.
- •Accessible tumor lesion/metastasis for tumor collection.
- •Willingness of the patient to undergo a surgical intervention (eg, surgical resection and/or biopsy) to collect one or more tumor lesions/metastases.
- •Adequate organ function (pulmonary, cardiovascular, hematological, hepatic, and renal function) per investigator's judgment. Cardiac stress testing is required for all patients with underlying cardiac conditions and patients with age ≥ 50 years.
- •Negative serum pregnancy test in women of childbearing potential, in peri-menopausal women and in women with less than 2 years of menopause.
排除标准
- •Active central nervous system (CNS) metastases. Patients with stable CNS metastases ≥ 1 month after definitive treatment (eg, surgery and/or radiotherapy) are eligible.
- •Participants with an active second malignancy.
- •Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol, including autoimmune or immunodeficient conditions, significant pulmonary disease, significant cardiac and/or vascular disease per investigator's judgment.
- •Prior immune-related adverse events that would preclude re-challenge with an immune checkpoint inhibitor or immunomodulatory agent per investigator's judgment.
- •Immunosuppressive treatment that would preclude the patient from any of the study therapies per investigator's judgment.
- •Severe active infections or uncontrolled infectious conditions requiring treatment.
- •Any other conditions/diseases, allergies, dysfunctions, and/or findings, that would contraindicate the use of any of the study interventions or therapies.
- •Contraindication for any of the planned measures, interventions and/or treatments.
- •Pregnant or breastfeeding women, or female subject who are not willing to use an acceptable, highly effective method of contraception until the End-of-Study visit.
- •Known hypersensitivity to any of study therapies or drugs used for TIL production.
- •Known human immunodeficiency virus (HIV) infection (or tests positive for HIV 1 or 2 at Screening).
- •Known hepatitis B or hepatitis C infection.
研究组 & 干预措施
Tumor-infiltrating lymphocyte product (TIL) transfer
Tumor-specific T cells are expanded from excised tumor samples and stimulated in cell culture with interleukin-2 (IL-2). The resulting autologous TILs are then re-infused to the patient after a non-myeloablative lymphodepleting chemotherapy with cyclophosphamide and fludarabine. Activation of TILs in the patient is then supported by IL-2 administration. The transplant product will be produced in the Good Manufacturing Practice (GMP) facility of the University Hospital in Basel.
干预措施: TILs（Tumor Infiltrating Lymphocytes） (Drug)
结局指标
主要结局
Progression-free rate at 6 months after Tumor-infiltrating lymphocytes transfer.
时间窗: 5-7 months after TIL transfer
Progression-free rate (PFR) (RECIST v1.1 / iRECIST) at 6 months after TIL transfer, defined by the Kaplan-Meier estimator for progression-free survival (RECIST v1.1 / iRECIST) at 6 months (+/- 4 weeks as we allow this interval in the tumor assessment at 6 months).
次要结局
- Duration of response (DOR)(up to one year after TIL transfer)
- Frequency of adverse events (number)(up to one year after TIL transfer)
- Incidence of adverse events (%)(up to one year after TIL transfer)
- Objective response rate (ORR)(up to one year after TIL transfer)
- Severity of adverse events (CTCAE v5.0 criteria)(up to one year after TIL transfer)
- Overall survival (OS)(up to one year after TIL transfer)
- Progression-free survival (PFS)(up to one year after TIL transfer)