Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.
- Conditions
- Cutaneous Squamous Cell Carcinoma (CSCC)
- Interventions
- Registration Number
- NCT07064330
- Lead Sponsor
- Instituto de Investigación Biomédica de Salamanca
- Brief Summary
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.
- Detailed Description
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.
Endpoints and Data Analysis Clinical response will be measured using RECIST 1.1, and toxicity will follow CTCAE v5.0. Statistical analyses will correlate immune profiles with outcomes using appropriate tests (e.g., chi-square, t-tests, ANOVA, Kaplan-Meier survival analysis).
Ethical Considerations The study complies with the Declaration of Helsinki, GCP, and GDPR. Informed consent is mandatory, and data confidentiality is ensured. Samples and data will only be used for approved research purposes.
Impact The NGF-GRACE project seeks to advance precision immunotherapy in CSCC by identifying predictive biomarkers that can improve patient selection, predict adverse events, and inform new therapeutic strategies. The study's innovative technologies and comprehensive design position it to fill critical knowledge gaps in CSCC immuno-oncology.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Observational Cohort Cemiplimab 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.
- Primary Outcome Measures
Name Time Method Biomarker signature associated with cemiplimab response 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) 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 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.
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) Up to 18 months Time from cemiplimab initiation to disease progression or death from any cause.
Overall Survival (OS) Up to 24 months Time from cemiplimab initiation to death from any cause.
Analysis of transcriptomic and proteomic immune profiling of tumor-infiltrating cells From pre-treatment biopsy to post-infusion sample (up to 3 months) Single-cell analysis of tumor samples before and during treatment, identifying profiles associated with response or resistance.
Correlation between tumor and blood immune biomarkers Up to 6 months Association between immune signatures in peripheral blood and those found in the tumor microenvironment. 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.
Treatment discontinuation due to toxicity From first dose to end of treatment (up to 12 months) Rate and reasons for cemiplimab discontinuation related to adverse events.
Related Research Topics
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Trial Locations
- Locations (1)
Complejo Asistencial Universitario de Salamanca
🇪🇸Salamanca, Spain
Complejo Asistencial Universitario de Salamanca🇪🇸Salamanca, Spain