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NCT06568172

Testing the Addition of an Immunotherapy Drug, Cemiplimab (REGN2810), Plus Surgery to the Usual Surgery Alone for Treating Advanced Skin Cancer

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

420 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-02-18

Study Completion Date

2031-08-14

Brief Summary

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This phase III trial compares the effect of adding cemiplimab to standard therapy (surgery with or without radiation) versus standard therapy alone in treating patients with stage III/IV squamous cell skin cancer that is able to be removed by surgery (resectable) and that may have come back after a period of improvement (recurrent). The usual treatment for patients with resectable squamous cell skin cancer is the removal of the cancerous tissue (surgery) with or without radiation, which uses high energy x-rays, particles, or radioactive seeds to kill cancer cells and shrink tumors. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cemiplimab has been approved for the treatment of skin cancer that has spread or that cannot be removed by surgery, but it has not been approved for the treatment of skin cancer than can be removed by surgery. Adding cemiplimab to the usual treatment of surgery with or without radiation may be more effective in treating patients with stage III/IV resectable squamous cell skin cancer than the usual treatment alone.

Detailed Description

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PRIMARY OBJECTIVE:

I. To determine if neoadjuvant immunotherapy combined with response-adapted oncologic surgery improves site-reported event-free survival (EFS) compared to standard-of-care surgery in resectable stage III/IV cutaneous squamous cell carcinoma (CSCC).

SECONDARY OBJECTIVES:

I. To compare utilization of adjuvant radiation between arms. II. To compare disease-free survival (DFS) between arms. III. To compare overall survival (OS) between arms. IV. To compare adverse events (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v\]5.0) between arms.

V. To assess pathologic complete response in arm 2.

PATIENT-REPORTED OUTCOMES:

I. Compare changes in patient reported quality of life as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) at 1, 6, and 12 months after surgery between treatment arms. (Primary objective) II. To compare patient reported symptoms functioning, and quality of life, as measured by the Cutaneous Squamous Cell Carcinoma NeoAdjuvant, Adjuvant and Perioperative 32 question scale (CSCC NAAP-32), Patient Reported Outcomes Measurement Information System (PROMIS)-Short Form (SF)-Anxiety, PROMIS-SF-Fatigue, and EuroQol-5D (EQ-5D), between arms at 1, 6, and 12 months after surgery.

III. Develop a scoring algorithm and validate the CSCC-NAAP-32 for use in this patient population.

EXPLORATORY OBJECTIVES:

I. To compare disease-specific survival (DSS) between arms. II. To correlate pathologic response with DFS in arm 2. III. To assess overall response rate (ORR) in arm 2. IV. To compare patterns of failure between arms. V. To compare pathologic measurements of lymph node yield between arms. VI. To compare primary tumor specimen dimensions and volume between arms.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1: Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 6-12 weeks of surgery, patients may undergo image-guided radiation therapy (IGRT) with intensity modulated radiation therapy (IMRT) for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET)/CT prior to treatment, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

ARM 2: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo response-adaptive surgery 21 days after last dose of cemiplimab. Starting within 12 weeks of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Starting within 6 weeks of completion of surgery or radiation therapy (if indicated), patients without pathologic complete response (pCR) receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET/CT prior to treatment, and CT and/or MRI on study and during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

After completion of study treatment, patients are followed up at 1, 6, and 12 months post-surgery then every 3 months for 2 years, every 6 months in year 3, and then annually thereafter.

Conditions

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Eyelid Squamous Cell Carcinoma Recurrent Eyelid Squamous Cell Carcinoma Recurrent Skin Acantholytic Squamous Cell Carcinoma Recurrent Skin Clear Cell Squamous Cell Carcinoma Recurrent Skin Lymphoepithelial Carcinoma Recurrent Skin Spindle Cell Squamous Cell Carcinoma Recurrent Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation Resectable Eyelid Squamous Cell Carcinoma Resectable Skin Acantholytic Squamous Cell Carcinoma Resectable Skin Clear Cell Squamous Cell Carcinoma Resectable Skin Lymphoepithelial Carcinoma Resectable Skin Spindle Cell Squamous Cell Carcinoma Resectable Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation Skin Acantholytic Squamous Cell Carcinoma Skin Clear Cell Squamous Cell Carcinoma Skin Lymphoepithelial Carcinoma Skin Spindle Cell Squamous Cell Carcinoma Skin Squamous Cell Carcinoma With Sarcomatoid Differentiation Stage III Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8 Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

A central review of 40% of patients who experience a recurrence or progression that is considered a primary endpoint event will be conducted once the number of events for the primary endpoint has been reached. Each case will be reviewed by two independent reviewers who are blinded to the patient's assigned treatment arm.

Study Groups

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Arm 1 (surgery, radiation)

Patients undergo surgery per standard of care within 6 weeks of randomization. Starting within 6-12 weeks of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Patients also undergo CT, MRI, and/or PET/CT prior to treatment, and CT and/or MRI during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

Group Type ACTIVE_COMPARATOR

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood and/or plasma

Computed Tomography

Intervention Type PROCEDURE

Undergo CT and/or PET/CT

Image Guided Radiation Therapy

Intervention Type RADIATION

Undergo IGRT

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo IMRT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Surgical Procedure

Intervention Type PROCEDURE

Undergo surgery per SOC

Arm 2 (cemiplimab, surgery, radiation)

Patients receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo response-adaptive surgery 21 days after last dose of cemiplimab. Starting within 12 weeks of surgery, patients may undergo IGRT with IMRT for 5 fractions per week for 6 weeks as clinically indicated. Starting within 6 weeks of completion of surgery or radiation therapy (if indicated), patients without pCR receive cemiplimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 42 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and/or PET/CT prior to treatment, and CT and/or MRI on study and during follow up. Patients may also undergo optional collection of tissue, whole blood, and plasma on study.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood and/or plasma

Cemiplimab

Intervention Type BIOLOGICAL

Given IV

Computed Tomography

Intervention Type PROCEDURE

Undergo CT and/or PET/CT

Image Guided Radiation Therapy

Intervention Type RADIATION

Undergo IGRT

Intensity-Modulated Radiation Therapy

Intervention Type RADIATION

Undergo IMRT

Magnetic Resonance Imaging

Intervention Type PROCEDURE

Undergo MRI

Positron Emission Tomography

Intervention Type PROCEDURE

Undergo PET/CT

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Surgical Procedure

Intervention Type PROCEDURE

Undergo response-adaptive surgery

Interventions

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Biospecimen Collection

Undergo collection of blood and/or plasma

Intervention Type PROCEDURE

Cemiplimab

Given IV

Intervention Type BIOLOGICAL

Computed Tomography

Undergo CT and/or PET/CT

Intervention Type PROCEDURE

Image Guided Radiation Therapy

Undergo IGRT

Intervention Type RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

Intervention Type RADIATION

Magnetic Resonance Imaging

Undergo MRI

Intervention Type PROCEDURE

Positron Emission Tomography

Undergo PET/CT

Intervention Type PROCEDURE

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Surgical Procedure

Undergo surgery per SOC

Intervention Type PROCEDURE

Surgical Procedure

Undergo response-adaptive surgery

Intervention Type PROCEDURE

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection Cemiplimab RWLC Cemiplimab-rwlc Libtayo REGN 2810 REGN-2810 REGN2810 CAT CAT Scan Computed Axial Tomography Computerized Axial Tomography Computerized axial tomography (procedure) Computerized Tomography Computerized Tomography (CT) scan CT CT Scan Diagnostic CAT Scan Diagnostic CAT Scan Service Type tomography IGRT Image Guided Radiotherapy image-guided radiation therapy Image-Guided Radiotherapy IMRT Intensity modulated radiation therapy (procedure) Intensity Modulated RT Intensity-Modulated Radiotherapy Radiation, Intensity-Modulated Radiotherapy Magnetic Resonance Magnetic Resonance Imaging (MRI) Magnetic resonance imaging (procedure) Magnetic Resonance Imaging Scan Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance MR MR Imaging MRI MRI Scan MRIs NMR Imaging NMRI Nuclear Magnetic Resonance Imaging sMRI Structural MRI Medical Imaging, Positron Emission Tomography PET PET Scan Positron emission tomography (procedure) Positron Emission Tomography Scan Positron-Emission Tomography PT Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery Operation Surgery Surgery Type Surgery, NOS Surgical Surgical Intervention Surgical Interventions Surgical Procedures Type of Surgery

Eligibility Criteria

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Inclusion Criteria

* Pathologically (histologically or cytologically) proven diagnosis of invasive cutaneous squamous cell carcinoma (CSCC) or regional lymph node or in-transit metastasis of CSCC

* The following CSCC subtypes are eligible according to World Health Organization (WHO) classification if the predominant histology is confirmed CSCC.

* Spindle cell squamous cell carcinoma (SCC)
* Squamous cell carcinoma with sarcomatoid differentiation
* Acantholytic SCC
* Clear cell SCC
* Lymphoepithelial carcinoma

* Note: Keratoacanthoma SCC and Verrucous SCC subtypes are not eligible.
* For patients with regional metastasis without a primary tumor at screening: a clinical history of CSCC that drains to the involved regional lymph nodes or in-transit metastases in question is required

* For example, a parotid mass shown to be SCC by cytologic analysis of a fine needle aspirate in a patient with a clinical history of CSCC on the ipsilateral scalp would be eligible
* For patients with regional metastases without a primary tumor and an ambiguous clinical history: tumor genomic sequencing suggesting a primary tumor of cutaneous origin would be acceptable evidence to establish eligibility
* NOTE: Tumor genomic sequencing is not required to determine eligibility, but may be part of the routine evaluation of patients with cancers of unknown primary at some institutions. For example, a parotid mass shown to be SCC by cytologic analysis of fine needle aspirate without a primary tumor and an ambiguous clinical history, but with a tumor genomic sequencing assay demonstrating a high tumor mutation burden (≥ 10 mutations/Mb) and/or a high fraction of ultraviolet (UV) related mutations (\> 50% of mutations \[cytosine (C)/thymine (T)\]C \> T or CC \> TT) and/or the presence of "signature 7" mutations would be eligible (Chang 2021)
* Previously untreated or recurrent CSCC
* Clinical American Joint Committee on Cancer (AJCC) 8th Edition (eyelid, head and neck sites) or Union for International Cancer Control (UICC) (non-head and neck sites) stage III or IV
* Primary tumor site must be in the head and neck cutaneous region, other non-head and neck cutaneous regions, or eyelid cutaneous region
* No mucosal squamous cell carcinoma (vermillion lip, nasal, oral, sinonasal, conjunctival, anogenital)
* Tumor must be resectable with curative intent. Note: Tumor with bony skull base invasion and/or skull base foramen involvement (T4b) is not eligible. (Patients with T4b eyelid tumors using UICC Staging, and not involving the brain, are eligible.)
* At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
* No definitive clinical or radiologic evidence of distant metastatic disease (M1), visceral and/or distant nodal disease
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Not pregnant and not nursing

* Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal
* Absolute neutrophil count (ANC) ≥ 1,000 cells/mm\^3
* Platelets ≥ 75,000 cells/mm\^3
* Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve hemoglobin \[Hgb\] ≥ 8.0 g/dl is acceptable)
* Creatinine clearance (CrCL) \> 30mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (NOTE: For patients with Gilbert's syndrome, total bilirubin ≤ 3 x ULN. Gilbert's syndrome must be documented appropriately as past medical history.)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional ULN
* No prior systemic therapy for the study cancer (including patients currently receiving immunotherapy for a separate malignancy)
* No prior radiotherapy to the region of the study cancer that would result in cumulative doses of radiation to organs at risk for radiation injury that exceed protocol limitations
* No history of myocardial infarction/unstable angina within the last 6 months
* New York Heart Association functional classification IIb or better (New York Heart Association \[NYHA\] functional classification III/IV are not eligible) (Note: Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association functional classification)
* No active infection requiring systemic antibiotics, antiviral, or antifungal treatments
* No history of allogeneic stem cell transplantation, or autologous stem cell transplantation
* No history of a solid organ transplant (other than corneal transplant)
* No active, known, or suspected autoimmune disease

* Active or known disease is defined as:

* Requiring higher than physiologic steroid levels (\> 10mg prednisone/day or equivalent) or
* Requiring disease-modifying agents or
* Ongoing or recent (within 5 years prior to registration) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs)
* NOTES:

* Patients meeting the following criteria are not considered immunosuppressed and are eligible to enroll:

* Patients who require a brief course of steroids (eg, prophylaxis for imaging assessments due to hypersensitivity to contrast agents) are not excluded
* Patients with type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, or skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
* Physiologic replacement doses ≤ 10 mg prednisone/day or equivalent allowed, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted
* Patients with the following immunosuppressed conditions are eligible to enroll:

* Patients with HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible
* Patients with chronic lymphocytic leukemia (CLL) with no history of anti-CLL therapy within 6 months prior to registration are eligible
* No history of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia)
* No active, noninfectious pneumonitis requiring immune-suppressive therapy
* No active tuberculosis
* No live vaccines within 28 days prior to registration
* No history of allergic reaction to the study agent, compounds of similar chemical or biologic composition to the study agent (or any of its excipients)

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neil D Gross

Role: PRINCIPAL_INVESTIGATOR

NRG Oncology

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status RECRUITING

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

Site Status RECRUITING

Tower Cancer Research Foundation

Beverly Hills, California, United States

Site Status RECRUITING

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Site Status RECRUITING

UC San Diego Health System - Encinitas

Encinitas, California, United States

Site Status RECRUITING

City of Hope at Irvine Lennar

Irvine, California, United States

Site Status RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, United States

Site Status RECRUITING

City of Hope Antelope Valley

Lancaster, California, United States

Site Status RECRUITING

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, United States

Site Status RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

Kaiser Permanente-Oakland

Oakland, California, United States

Site Status RECRUITING

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Kaiser Permanente-South Sacramento

Sacramento, California, United States

Site Status RECRUITING

UC San Diego Medical Center - Hillcrest

San Diego, California, United States

Site Status RECRUITING

City of Hope South Pasadena

South Pasadena, California, United States

Site Status RECRUITING

Torrance Memorial Physician Network - Cancer Care

Torrance, California, United States

Site Status RECRUITING

City of Hope Upland

Upland, California, United States

Site Status RECRUITING

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Site Status RECRUITING

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Site Status RECRUITING

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Site Status RECRUITING

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Site Status RECRUITING

Helen F Graham Cancer Center

Newark, Delaware, United States

Site Status RECRUITING

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

Site Status RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Site Status RECRUITING

Miami Cancer Institute

Miami, Florida, United States

Site Status RECRUITING

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Site Status RECRUITING

Sarasota Memorial Hospital-Venice

N. Venice, Florida, United States

Site Status RECRUITING