NCT07064330

Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.

Next Generation Flow Cytometry for Global Immunological Profile, Response And Toxicity Biomarker Signatures in Cutaneous Squamous Cell Carcinoma Under CEmiplimab Treatment.

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 30 (estimated)
• Sponsor: Instituto de Investigación Biomédica de Salamanca · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Cutaneous Squamous Cell Carcinoma (CSCC)

Interventions

Type	Name	Description
DRUG	Cemiplimab	350 mg IV every 3 weeks as per standard of care. Patients are observed prospectively for biomarkers of response and toxicity during cemiplimab treatment.

Timeline

• Start date: 2025-07-17
• Primary completion: 2027-06-01
• Completion: 2027-06-01
• First posted: 2025-07-14
• Last updated: 2025-09-10

Locations

1 site across 1 country: Spain