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NCT06568172

PHASE3

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

Sponsor: National Cancer Institute (NCI)

View on ClinicalTrials.gov

Summary

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.

Official title: Randomized Phase III Trial of Neoadjuvant Immunotherapy With Response-Adapted Treatment Versus Standard-of-Care Treatment for Resectable Stage III/IV Cutaneous Squamous Cell Carcinoma (C-PRE)

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

420

Start Date

2025-02-18

Completion Date

2031-08-14

Last Updated

2026-11-03

Healthy Volunteers

Conditions

Interventions

PROCEDURE

Biospecimen Collection

Undergo collection of blood and/or plasma

BIOLOGICAL

Cemiplimab

Given IV

PROCEDURE

Computed Tomography

Undergo CT and/or PET/CT

RADIATION

Image Guided Radiation Therapy

Undergo IGRT

RADIATION

Intensity-Modulated Radiation Therapy

Undergo IMRT

PROCEDURE

Magnetic Resonance Imaging

Undergo MRI

PROCEDURE

Positron Emission Tomography

Undergo PET/CT

OTHER

Questionnaire Administration

Ancillary studies

PROCEDURE

Surgical Procedure

Undergo surgery per SOC

PROCEDURE

Surgical Procedure

Undergo response-adaptive surgery

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)

Locations (206)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, United States

Tower Cancer Research Foundation

Beverly Hills, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

UC San Diego Health System - Encinitas

Encinitas, California, United States

City of Hope at Irvine Lennar

Irvine, California, United States

UC San Diego Moores Cancer Center

La Jolla, California, United States

City of Hope Antelope Valley

Lancaster, California, United States

The Angeles Clinic and Research Institute - West Los Angeles Office

Los Angeles, California, United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Kaiser Permanente-South Sacramento

Sacramento, California, United States

UC San Diego Medical Center - Hillcrest

San Diego, California, United States

Kaiser Permanente-San Francisco

San Francisco, California, United States

City of Hope South Pasadena

South Pasadena, California, United States

Torrance Memorial Physician Network - Cancer Care

Torrance, California, United States

City of Hope Upland

Upland, California, United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California, United States

UCHealth University of Colorado Hospital

Aurora, Colorado, United States

UCHealth Memorial Hospital Central

Colorado Springs, Colorado, United States

Memorial Hospital North

Colorado Springs, Colorado, United States

Smilow Cancer Hospital Care Center at Greenwich

Greenwich, Connecticut, United States

Smilow Cancer Hospital Care Center - Guilford

Guilford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, United States

Smilow Cancer Hospital-Waterbury Care Center

Waterbury, Connecticut, United States

Smilow Cancer Hospital Care Center - Waterford

Waterford, Connecticut, United States

Helen F Graham Cancer Center

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

Newark, Delaware, United States

UM Sylvester Comprehensive Cancer Center at Aventura

Aventura, Florida, United States

UM Sylvester Comprehensive Cancer Center at Coral Gables

Coral Gables, Florida, United States

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Deerfield Beach, Florida, United States

UM Sylvester Comprehensive Cancer Center at Doral

Doral, Florida, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

UM Sylvester Comprehensive Cancer Center at Kendall

Miami, Florida, United States

Sarasota Memorial Hospital-Venice

N. Venice, Florida, United States

UM Sylvester Comprehensive Cancer Center at Plantation

Plantation, Florida, United States

Florida Cancer Specialists - Sarasota