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

NCT07064330 | Recruiting

• 2 other identifiers: NGF-GRACE StudyE.O. 24/841
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Cutaneous Squamous Cell Carcinoma (CSCC)

Keywords

Cemiplimab; Rhapsody Single Cell System; Tumor Microenvironment

Outcome Measures

Primary Outcomes (3)

• Biomarker signature associated with cemiplimab response

  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.

  Up to 6 months from treatment initiation

• Best Overall Response (BOR)

  Proportion of patients with complete response (CR) or partial response (PR) according to RECIST v1.1 criteria, as assessed during cemiplimab treatment.

  From baseline to end of treatment (up to 12 months)

• Immune-related toxicity rate

  Descripción: Incidence and severity of immune-related adverse events (irAEs) according to CTCAE v5.0, and their association with baseline immune profiles.

  From first infusion until 90 days after last dose of cemiplimab

Secondary Outcomes (5)

• 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)

Other Outcomes (2)

• Change in immune cell subpopulations over time

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

• Change in soluble immune markers over time

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months

Study Arms (1)

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.

Drug: Cemiplimab

Interventions

Cemiplimab DRUG

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

Observational Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Every patient who is going to be treated with cemiplimab is a potential candidate for this study considering the inclusion and exclusion criteria of the registry study, included in SmPC.

You may qualify if:

• Hepatic function:
• Total bilirubin ≤1.5x upper limit of normal (ULN) (or ≤3x ULN, if liver metastases).
• Patients with Gilbert's Disease and total bilirubin up to 3x ULN may be eligible after communication with and approval from the medical monitor
• Transaminases ≤3x ULN (or ≤5x ULN, if liver metastases)
• Alkaline phosphatase (ALP) ≤2.5x ULN (or ≤5x ULN, if liver or bone metastases) Renal function: Serum creatinine ≤2x ULN or estimated creatinine clearance \>35 mL/min (according the method of Cockcroft and Gault) Creatine phosphokinase (CPK) (also known as CK \[creatine kinase\]) elevation ≤ grade 2
• Bone marrow function:
• a. Hemoglobin ≥9.0 g/dL b. Absolute neutrophil count (ANC) ≥1.5 x 109/L c. Platelet count ≥75 x 109/L Anticipated life expectancy \>12 weeks

You may not qualify if:

• \- Patient who refuses to participate in the study.
• Being unsuitable for cemiplimab treatment
• Untreated brain metastasis(es) that may be considered active.
• a. Note in clarification: Patients with previously treated brain metastases may participate provided that the lesion(s) is (are) stable (without evidence of progression for at least 6 weeks on imaging obtained in the screening period), and there is no evidence of new or enlarging brain metastases, and the patients do not require any immunosuppressive doses of systemic corticosteroids for management of brain metastasis(es) within 28 days of the first dose of REGN2810cemiplimab.
• Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of REGN2810cemiplimab
• a. Note in clarification: Patients who require brief courses of steroids (eg, as prophylaxis for imaging studies due to hypersensitivity to contrast agents) are not excluded
• Active infection requiring therapy, including positive tests for human immunodeficiency virus (HIV)-1 or HIV-2 serum antibody, hepatitis B virus (HBV), or hepatitis C virus (HCV)
• History of pneumonitis within the last 5 years
• Any anticancer treatment other than radiation therapy (chemotherapy, targeted systemic therapy, imiquimod, photodynamic therapy), investigational or standard of care, within 30 days of the initial administration of REGN2810 cemiplimab or planned to occur during the study period
• History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
• Patients with allergy or hypersensitivity to REGN2810 cemiplimab or to any of the excipients must be excluded.
• Patients with a history of solid organ transplant (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the medical monitor)
• Breastfeeding
• Receipt of live vaccines (including attenuated) within 30 days of first study treatment
• Women of childbearing potential (WOCBP)\*, or sexually active men, who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment prior to the start of the first treatment, during the study, and for at least 6 months after the last dose.

Sponsors & Collaborators

• Instituto de Investigación Biomédica de Salamanca: lead
• Regeneron Pharmaceuticals: collaborator
• Carlos III Health Institute: collaborator
• University of Salamanca: collaborator

Study Sites (1)

Complejo Asistencial Universitario de Salamanca

Salamanca, Salamanca, 37007, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole perypheral blood and tumor samples.

MeSH Terms

Interventions

cemiplimab

Study Officials

• Javier Cañueto, Medical Degree in Dermatology

  Centro Asistencial Universitario de Salamanca (CAUSA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ricardo López, Study Project Manager

CONTACT

+34923291200; uicec.gestion@ibsal.es

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2025
• First Posted: July 14, 2025
• Study Start: July 17, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, ANALYTIC CODE
• Time Frame: Data will be available starting 12 months after publication of primary results and for a minimum of 5 years thereafter.
• Access Criteria: Sharing Access Criteria: Qualified researchers with a methodologically sound proposal, as determined by the study steering committee, will be able to access the data. Requests should be directed to the study PI. A data access agreement will be required.

Locations

ES (1)