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

Paused · Phase 3

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT06568172

Run by

National Cancer Institute (NCI)

People needed

420

Starts

2025-02-18

Expected to finish

2031-08-14

Last updated by the study team

2026-08-04

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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

Where it is running

• 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
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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