A Phase I Study to Assess the Safety and Tolerability of ex Vivo Next-generation Neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) Therapy in Advanced Epithelial Tumors and Immune Checkpoint Blockade (ICB) Resistant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Incidence of alterations in vital signs measurements
研究概览
简要总结
Background:
The presence of T-lymphocytes in resected tumor samples derived from long-term survival patients and the fact that reinvigoration of their functionality through the administration of specific immune-therapies can lead to remarkable antitumor responses supports that lymphocytes play a critical role in cancer immunity.
Adoptive cell therapy using tumor-infiltrating lymphocytes product (TIL-ACT) is a well-established combination therapy currently under study in several world reference centers, using an autologous cell product without genetic modifications. This cell product consists of tumor-infiltrating lymphocytes (TIL), which are collected from the patient and expanded in the lab under specific conditions to enhance its antitumoral efficacy before reinfusion in the same patient. However, this cell product alone does not achieve adequate efficacy, and a combination of both previous non-myeloablative lymphodepleting (NMA-LD) chemotherapy and subsequent cytokine therapy (specifically IL-2) is needed to support the expansion of the infused cells.
The investigators hypothesize that TILs enriched for neoantigen recognition are superior to unselected TILs at mediating tumor regression in patients with epithelial tumors and even other solid tumors where immune checkpoint blockade (ICB) is approved and used as part of standard therapy. The investigators propose to manufacture a T-cell product composed of TILs that are selected based on their ability to recognize patient-specific neoantigens and to use these to treat patients with metastatic, refractory, epithelial cancers, as well as ICB-resistant solid tumors. Furthermore, it also proposed to study the tumor and T cells at baseline and after treatment to investigate whether specific phenotypic and functional traits may be associated with clinical outcome.
Primary objective:
To evaluate the safety and the tolerability of ex vivo next generation neoantigen-selected Tumor-infiltrating Lymphocyte (TIL) in patients with metastatic or unresectable epithelial tumors and immune checkpoint blockade (ICB) resistant solid tumors.
Secondary objectives:
- To determine the success in producing active specific TILs from our target patients.
- To evaluate the initial clinical activity of the NEXTGEN-TIL products in our target patients.
详细描述
Methods:
This study is a first-in-human, open-label, non-controlled, single-centre, phase I trial to assess the safety and tolerability of NEXTGEN-TIL-ACT. Given the exploratory nature of the study, there is no formal hypothesis testing and no formal sample size calculation was carried out.
A sample size of 10 patients has been selected to provide information about the frequency of treatment-limiting toxicity (TLT).
Study treatment:
The main study therapy is the Tumor-infiltrating Lymphocyte (NEXTGEN-TIL) product, which is preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion.
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 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
NEXTGEN-TIL
Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years.
干预措施: NEXTGEN-TIL (Biological)
NEXTGEN-TIL
Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years.
干预措施: Non-myeloablative Lymphodepletion (NMA-LD) Regimen (Drug)
NEXTGEN-TIL
Subjects will receive a therapy based on Tumor-infiltrating Lymphocyte (NEXTGEN-TIL product) preceded by a preparative non-myeloablative lymphodepleting (NMA-DL) regimen and followed by IL-2 infusion. Patients will be followed-up for 2 years, assessed at weeks 2, 3, 4, 6, 9, 12, 18, 24, 30, 36 (9 months), and then at 1 year, 1,5 and 2 years.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Incidence of alterations in vital signs measurements
时间窗: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in vital signs.
Incidence of Serious Adverse Events (SAE)
时间窗: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Nature and frequency of SAE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Incidence of alterations in clinical laboratory test results
时间窗: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in clinical laboratory test results
Incidence of physical examination findings
时间窗: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in the physical examination.
Assessment of performance status
时间窗: From baseline through study completion, an average of 2 years
Patient performance status assessed as per Eastern Cooperative Oncology Group (ECOG) score, where grade 0 is for fully active and capable patient and grade 5 is death.
Incidence of Adverse Events (AE)
时间窗: From baseline through 6 months from the last dose of IL-2 or until the first dose of the next anticancer therapy, whichever occurs first
Nature and frequency of AE, graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Treatment-limiting Toxicity (TLT)
时间窗: From the first dose of study treatment (Day -5) to 30 days after
Toxicities related to treatment administration that, if recurrent at high enough frequency (≥2 patients treated), should trigger review by the Independent Data Safety Monitoring Board (IDSMB), which could lead to recommendations for treatment modifications for subsequent patients.
Incidence of alterations in electrocardiogram assessment
时间窗: From baseline through study completion, an average of 2 years
Nature and frequency of abnormalities found in electrocardiogram
次要结局
- Neoantigen-selected TIL analysis(At baseline)
- Overall Response Rate (ORR)(From baseline through disease progression, assessed up to 36 months after last dose of IL-2)
- Duration of Response (DOR)(From baseline through disease progression, assessed up to 36 months after last dose of IL-2)
- Progression-Free Survival (PFS)(From baseline through disease progression, assessed up to 36 months after last dose of IL-2)
研究者
Phase I Director
Scientific
Vall D Hebron Institute Of Oncology