Mechanisms of Resistance to anti-PD-1 Therapy in cutaneous Squamous Cell Carcinomas: Impact of Tumor Cell Plasticity on Promoting Myeloid Suppressor Cell Infiltration. A phase II single arm, unicenter study of cemiplimab in patients with locally advanced cSCCs.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Diagnosis, Efficacy

To characterize the immune environment and tumor cell plasticity in patients with cutaneous squamous cell carcinoma (cSCC) treated with cemiplimab, in order to identify mechanisms of resistance to anti-PD-1 therapy and potential biomarkers or new therapeutic targets.

Secondary objectives 3

1. To characterize tumor and immune cell heterogeneity in pre-treated and post-treated samples of responders and non-responder advanced SCCs to anti-PD1 therapy by multiplexed immunohistochemistry assays.
2. To fully capture the heterogeneity of tumor cells and tumor-infiltrating immune cells in post-treated samples of responder and non-responder SCCs to anti-PD-1 therapy by flow cytometry and single-cell RNA sequencing.
3. To identify cytokine-mediated cross-talk between tumor cells and immune cells in non-responder SCC patients to anti-PD-1 therapy.

Conditions and MedDRA coding

Cutaneous squamous cell carcinoma (ccSCC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Male or female subjects ≥ 18 years old.
2. Written informed consent approved by the Independent Ethics Committee (IEC), prior to the performance of any trial activities.
3. Locally advanced cSCC (T2-4, N0, M0). Including both resectable and unresectable disease, with no selection based on resectability status, provided that patients meet Criterion 5 (adequate tumor tissue available for all planned biological analyses).
4. No prior systemic treatment for the cSCC.
5. Patients must have enough tumor size to allow performing all biological tests detailed in Section 5.1.
6. Eastern Cooperative Oncology Group performance-status (ECOG PS) score of 0 or 1.
7. Adequate organ and bone marrow function according parameters hepatic function, renal function, Creatine phosphokinase (CPK) and Bone marrow function.
8. Anticipated life expectancy >12 weeks.
9. Female subjects of childbearing potential (WOCBP) must provide a negative urine pregnancy test at screening, and must agree to use a medically accepted and highly effective birth control method for the duration of the study treatment and for 6 months after the last dose of study treatment.
10. For both male and female patients/partners: Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for 4 months after the last dose of study treatment.

Exclusion criteria 19

1. Untreated known brain metastasis(es) that may be considered active.
2. 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 cemiplimab or planned to occur during the study period.
3. Presence of cardiovascular disease, as defined by: a. New York Heart Association heart failure classifications of Class II, III, or IV; or myocardial infarction, or acute coronary syndrome within 12 months of first dose of study medication; or b. Transient ischemic attack or stroke within 1 year
4. Patients with a history of solid organ transplants (patients with prior corneal transplants may be allowed to enroll after discussion with and approval from the principal investigator).
5. Patients with allergy or hypersensitivity to cemiplimab or to any of the excipients must be excluded.
6. History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
7. Any condition that requires ongoing/continuous corticosteroid therapy (>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study medication. Participants who require a brief course of steroids (up to 2 days in the week before enrollment) or physiologic replacement are not excluded.
8. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments.
9. Any infection requiring hospitalization or treatment with IV anti-infectives within 2 weeks of first dose of study medication
10. Uncontrolled infection with HIV, hepatitis B or hepatitis C infection, diagnosis of immunodeficiency, and/or tuberculosis (active or latent).
11. History of pneumonitis within the last 5 years.
12. Receipt of a live vaccine within 4 weeks of start of study medication
13. Receipt of COVID-19 vaccination within 1 week of planned start of study medication or for which the planned COVID-19 vaccinations would not be completed 1 week prior to start of study medication.
14. Known hypersensitivity to the active substances or to any of the excipients.
15. 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 (refer to Appendix 3)
16. Positive serum pregnancy test or pregnant females.
17. Breastfeeding females.
18. Patients who have a known secondary malignancy that is progressing or has required active treatment within the past 2 years.
19. Any underlying medical or psychiatric disorder, which, in the opinion of the investigator, makes the administration of cemiplimab unsafe or interferes with the informed consent process or trial procedures.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary translational end points are immunologic, genomic, and pathological correlations of response to cemiplimab in blood and tumor samples.

Secondary endpoints 5

1. Flow cytometry assays
2. Multiplex immunohistochemistry
3. Single-cell RNA (scRNA) Seq assays
4. Progression-free survival (PFS)
5. Overall Response Rate (ORR) per RECIST 1.1

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Sponsor organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Address

Avinguda De La Gran Via De L'hospitalet 199

City

L'Hospitalet De Llobregat

Postcode

08908

Country

Spain

Scientific contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso

Public contact point

Organisation

Fundacio Institut D'Investigacio Biomedica De Bellvitge IDIBELL

Contact name

Yaiza Hermoso

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications