Next Generation Flow Cytometry for Global Immunological Profile, Response And Toxicity Biomarker Signatures in Cutaneous Squamous Cell Carcinoma Under CEmiplimab Treatment.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Biomarker signature associated with cemiplimab response
研究概览
简要总结
Cutaneous squamous cell carcinoma (CSCC) is the second most frequent cancer in humans, it exhibits a high tumor mutational burden and is more common in immunocompromised patients, which aimed to explore the impact of immunotherapy in this cancer. CSCC shows good response to anti-PD1 immunotherapy, and cemiplimab is the first FDA-approved and the only EMA-approved treatment for this tumor. However, 50% of patients won't respond to anti-PD1 and to date there is little evidence on the reasons for such a lack of effectiveness. Also, anti-PD1 immunotherapy is very safe, but some patients will develop adverse events, and anticipating severe adverse events might help in patients' management. The NGF-GRACE project aims to find biomarkers of response and toxicity, both in the blood and the tumor, using advanced technologies. The goal is to move towards more personalized treatments, better select patients, predict side effects, and improve our understanding of the immune system in CSCC.
详细描述
The NGF-GRACE project focuses on identifying biomarkers of response and toxicity in patients with advanced cutaneous squamous cell carcinoma (CSCC) undergoing anti-PD1 treatment, being cemiplimab the unique approved drug in Europe. CSCC, characterized by a high mutational burden and increased risk in immunosuppressed patients, has exhibited significant sensitivity to anti-PD1 immunotherapy. By employing cutting-edge technologies such as Next Generation Flow Cytometry and the BD Rhapsody Single Cell System, the study aims to assess the immunological profile in peripheral blood and in the tumor tissue. The ultimate goal is to advance towards a more individualized therapeutic approach, identifying biomarkers that enhance patient selection, anticipate adverse events, and address knowledge gaps in the CSCC tumor immunology.
Background and Rationale CSCC is a type of skin cancer with one of the highest mutational burdens among solid tumors, making it particularly sensitive to immunotherapy, especially PD-1 blockade. Cemiplimab, an anti-PD-1 antibody, has become the first FDA and EMA-approved treatment for advanced CSCC. However, response rates are variable, with around 50% of patients showing clinical benefit. There is an urgent need to identify predictive biomarkers to guide patient selection, anticipate toxicity, and understand resistance mechanisms.
Study Objectives The main objective is to identify biomarker of response and toxicity to cemiplimab in patients with advanced cutaneous squamous cell carcinoma
Study Design The study will enroll approximately 30 patients with locally advanced or metastatic CSCC who will start cemiplimab treatment. Peripheral blood and tumor samples will be collected. A preliminary phase with 5 patients will define optimal sampling timepoints.
Methods Peripheral blood will be analyzed using Next Generation Flow Cytometry (NGF), applying a custom-designed 40-color antibody panel to characterize innate and adaptive immune cells. Also, soluble biomarkers will be evaluated. Single-cell technologies will be implemented for tumor evaluation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Observational Cohort
All enrolled patients will receive cemiplimab as part of standard clinical care for advanced cutaneous squamous cell carcinoma (CSCC). Cemiplimab is not assigned by the study but is administered as per physician's decision in routine practice.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Biomarker signature associated with cemiplimab response
时间窗: Up to 6 months from treatment initiation
Identification of peripheral blood and tumor immune biomarkers (cellular and soluble) that correlate with objective response to cemiplimab. Immune biomarkers to be reported include: 1. Peripheral blood biomarkers (cellular and soluble): * Cellular biomarkers include: CD4⁺, CD8⁺ and T cells, B and plasma cells, NK cells, monocytes, dendritic cells and other myeloid populations, functional and checkpoint markers (e.g. PD-1, HLA-DR). * Soluble biomarkers (cytokines and chemokines): IL-2, IL-6, IL-10, IFN-γ, TNF-α, Chemokines (CXCL9, CXCL10, CCL2, and CCL5). 2. Tumor tissue biomarkers (single-cell multi-omics): * Cellular biomarkers: CD3, CD4, CD8, CD11c, CD14, CD16, CD19, CD25, CD27, CD28, CD45RA, CD56, CD62L, CD127, CD134, CD137, CD161, CD183, CD185, CD186, CD196, CD197, CD272, CD278, CD279, CD357, CD366, HLA-DR, IgD and IdM. * Transcriptomic biomarkers: Single-cell transcriptome data (WTA library) will be generated to explore gene expression profiles associated with immune response.
Best Overall Response (BOR)
时间窗: From baseline to end of treatment (up to 12 months)
Proportion of patients with complete response (CR) or partial response (PR) according to RECIST v1.1 criteria, as assessed during cemiplimab treatment.
Immune-related toxicity rate
时间窗: From first infusion until 90 days after last dose of cemiplimab
Descripción: Incidence and severity of immune-related adverse events (irAEs) according to CTCAE v5.0, and their association with baseline immune profiles.
次要结局
- Progression-Free Survival (PFS)(Up to 18 months)
- Overall Survival (OS)(Up to 24 months)
- Analysis of transcriptomic and proteomic immune profiling of tumor-infiltrating cells(From pre-treatment biopsy to post-infusion sample (up to 3 months))
- Correlation between tumor and blood immune biomarkers(Up to 6 months)
- Treatment discontinuation due to toxicity(From first dose to end of treatment (up to 12 months))