Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma

NCT ID: NCT03969004

Last Updated: 2025-09-19

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

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

415 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-04

Study Completion Date

2028-03-26

Brief Summary

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The primary objective of the study is to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT).

The secondary objectives of the study are:

* To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT
* To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT
* To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT
* To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT
* To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT
* To assess cemiplimab pharmacokinetics and immunogenicity in human serum

Detailed Description

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Cemiplimab is a monoclonal antibody. Antibodies are proteins naturally found in the blood. A monoclonal antibody is a special antibody that is manufactured as a medication to target specific proteins in the body that may be involved in cancer. Cemiplimab works by blocking programmed death-1 (PD-1), a cell receptor on immune cells. By blocking PD-1, it is expected that the immune cells will attack cancer cells.

The study is being conducted in participants that have had surgery and radiation therapy for a type of skin cancer called cutaneous squamous cell cancer, and who have a risk that this cancer may come back.

The main purpose of the study is to determine if cemiplimab will prevent cutaneous squamous cell cancer (CSCC) from returning after surgery and radiation. Currently, we know that certain types of CSCC have a high chance of coming back after surgery and radiation. At this time, there is no approved treatment to give patients after surgery and radiation to prevent high-risk CSCC from coming back. We are investigating if the addition of cemiplimab will decrease the chance of these high-risk cancers coming back.

The study will also investigate if cemiplimab may help participants live for longer.

The study has two parts. Part 1: participants will receive every 3 weeks via intravenous infusion (drip into a vein) either cemiplimab (study drug) or placebo (similar to the study drug but without active medicine). After 12 weeks of treatment, cemiplimab or placebo will be given every 6 weeks. Part 1 of the study includes a screening period (up to 28 days), a treatment period (approximately 48 weeks), an end of treatment visit (approximately 30 days after completion of study drug treatment period) and a post-treatment follow-up period (approximately up to 5 years or until skin cancer returns or the study ends).

Part 2 of the study is optional and provides the participant with the option to receive cemiplimab if the cancer comes back if the participant was initially receiving placebo. There is no placebo in Part 2 of the study. If the cancer comes back, the study doctor will discuss with participants if they are eligible to participate in the optional part 2 of the study.

Part 2 of the study includes a brief screening period, a treatment period (approximately 96 weeks) and an end of treatment visit (approximately 30 days after the completion of the study drug treatment period).

Conditions

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Cutaneous Squamous Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Cemiplimab

Group Type EXPERIMENTAL

Cemiplimab

Intervention Type DRUG

Intravenous (IV) infusion over 30 minutes

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Intravenous (IV) infusion over 30 minutes

Interventions

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Cemiplimab

Intravenous (IV) infusion over 30 minutes

Intervention Type DRUG

Placebo

Intravenous (IV) infusion over 30 minutes

Intervention Type DRUG

Other Intervention Names

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REGN2810 Libtayo

Eligibility Criteria

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Inclusion Criteria

* For Japan only, men and women ≥21 years old
* Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease
* High risk CSCC, as defined in the protocol
* Completion of curative intent post-operative radiation therapy (RT) within 2 to 10 weeks of randomization
* Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1
* Adequate hepatic, renal, and bone marrow function as defined in the protocol

Exclusion Criteria

* Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol
* Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol
* Patients with hematologic malignancies (note: patients with chronic lymphocytic leukemia (CLL) are not excluded if they have not required systemic therapy for CLL within 6 months of enrollment)
* Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary)
* Ongoing or recent (within 5 years of randomization date) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
* Has had prior systemic anti-cancer immunotherapy for CSCC
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trial Management

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

Site Status

Mayo Clinic Hospital

Phoenix, Arizona, United States

Site Status

Regeneron Study Site

Tucson, Arizona, United States

Site Status

The Angeles Clinic

Los Angeles, California, United States

Site Status

University of Southern California (USC)

Los Angeles, California, United States

Site Status

Stanford Cancer Institute, Stanford Medicine at Stanford University

Palo Alto, California, United States

Site Status

University Of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

George Washington University School of Medicine and Health Sciences

Washington D.C., District of Columbia, United States

Site Status

University of Florida Health

Gainesville, Florida, United States

Site Status

Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, United States

Site Status

University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Regeneron Study Site

Atlanta, Georgia, United States

Site Status

Regeneron Study Site

Chicago, Illinois, United States

Site Status

Regeneron Study Site

Louisville, Kentucky, United States

Site Status

Regeneron Study Site

Baltimore, Maryland, United States

Site Status

Massachusetts General Cancer Center

Boston, Massachusetts, United States

Site Status

Dana Farber/Harvard Cancer Center

Boston, Massachusetts, United States

Site Status

Michigan Medicine- University of Michigan

Ann Arbor, Michigan, United States

Site Status

University of Missouri Health Care - University Physicians - Medicine Specialty Clinic

Columbia, Missouri, United States

Site Status

Washington University in Saint Louis

St Louis, Missouri, United States

Site Status

Nebraska Methodist Hospital

Omaha, Nebraska, United States

Site Status

Memorial Sloan Kettering

Basking Ridge, New Jersey, United States

Site Status

Memorial Sloan Kettering

Middletown, New Jersey, United States

Site Status

Memorial Sloan Kettering

Montvale, New Jersey, United States

Site Status

Memorial Sloan Kettering

New Brunswick, New Jersey, United States

Site Status

Memorial Sloan Kettering

Commack, New York, United States

Site Status

Memorial Sloan Kettering

Harrison, New York, United States

Site Status

NYU Langone Health

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Memorial Sloan Kettering

Uniondale, New York, United States

Site Status

Regeneron Research Site

Cincinnati, Ohio, United States

Site Status

The Ohio State University

Gahanna, Ohio, United States

Site Status

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Research Institute - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Texas Oncology - Baylor Charles A. Simmons Cancer Center

Dallas, Texas, United States

Site Status

UT Southwestern Medical Center

Dallas, Texas, United States

Site Status

University Of Virginia Health System

Charlottesville, Virginia, United States

Site Status

The Border Cancer Hospital Dispensary - Albury Wodonga Regional Cancer Centre

Albury, New South Wales, Australia

Site Status

Coffs Harbour Health Campus

Coffs Harbour, New South Wales, Australia

Site Status

Central Coast Cancer Centre-Gosford and Wyong Hospitals

Gosford, New South Wales, Australia

Site Status

St George Hospital

Kogarah, New South Wales, Australia

Site Status

North Shore Private Hospital

St Leonards, New South Wales, Australia

Site Status

Cancer Care Associates (CCA) Riverina Cancer Care Centre (RCCC)

Wagga Wagga, New South Wales, Australia

Site Status

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Site Status

Westmead Hospital

Westmead, New South Wales, Australia

Site Status

Illawarra Cancer Care Centre (ICCC)

Wollongong, New South Wales, Australia

Site Status

Melanoma Institute

Sydney, North South Wales, Australia

Site Status

Wide Bay Hospital and Health Service - Cancer Care Services

Bundaberg, Queensland, Australia

Site Status

Cairns Hospital

Cairns, Queensland, Australia

Site Status

The Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Site Status

ICON Cancer Care

Southport, Queensland, Australia

Site Status

Toowoomba Hospital

Toowoomba, Queensland, Australia

Site Status

Genesis Care Tugun - John Flynn Private Hospital

Tugun, Queensland, Australia

Site Status

Wide Bay Hospital and Health Service - Cancer Care Services - Hervey Bay

Urraween, Queensland, Australia

Site Status

Princess Alexandra Hospital

Woolloongabba, Queensland, Australia

Site Status

Ashford Cancer Centre Research-Adelaide Cancer Centre

Kurralta Park, South Australia, Australia

Site Status

Royal Hobart Hospital-Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Royal Hobart Hospital

Hobart, Tasmania, Australia

Site Status

Bendigo Health

Bendigo, Victoria, Australia

Site Status

St. Vincent's Hospital

Fitzroy, Victoria, Australia

Site Status

Olivia Newton -John Cancer Wellness & Research Centre

Heidelberg, Victoria, Australia

Site Status

Peter Maccallum Cancer Centre (PMCC)

Melbourne, Victoria, Australia

Site Status

Sir Charles Gairdner Hospital

Nedlands, Western Australia, Australia

Site Status

Royal Adelaide Hospital

Adelaide, , Australia

Site Status

Liverpool Cancer Therapy Center

Liverpool, , Australia

Site Status

University of New South Wales (UNSW) - Liverpool Hospital - Liverpool Cancer Therapy Centre

Liverpool, , Australia

Site Status

The Townsville Hospital and Health Service

Townsville, , Australia

Site Status

Universitair Ziekenhuis Leuven Gasthuisberg Campus

Leuven, Vlaams-Brabant, Belgium

Site Status

Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

Fundacao Sao Francisco Xavier - Hospital Marcio Cunha (HMC) - Unidade I

Ipatinga, Minas Gerais, Brazil

Site Status

Fundacao Pio XII - Hospital de Cancer de Barretos

Barretos, Porte Alegre, Brazil

Site Status

Instituto Nacional de Cancer Jose Alencar Gomes da Silva ¿ INCA

Santo Cristo, Rio de Janiero, Brazil

Site Status

Hospital Sao Vicente de Paulo (HSVP)

Passo Fundo, Rio Grande do Sul, Brazil

Site Status

Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS

Porto Alegre, Rio Grande do Sul, Brazil

Site Status

Centro De Novos Tratamentos Itajai

Itajaí, Santa Catarina, Brazil

Site Status

ANIMI

Lages, Santa Catarina, Brazil

Site Status

Centro Oncologico Mogi das Cruzes

Mogi das Cruzes, São Paulo, Brazil

Site Status

Hospital das Clinicas da Faculdade de Medician de Ribeirao Preto FMRP USP

Ribeirão Preto, São Paulo, Brazil

Site Status

Ynova pesquisa clinica

Florianópolis, , Brazil

Site Status

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, , Brazil

Site Status

University Health Network- Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Universitaire (CHU) de Dijon - Hopital du Bocage

Dijon, Dijon Cedex, France

Site Status

Hopital Saint Andre - CHU de Bordeaux

Bordeaux, , France

Site Status

Hopital Ambroise Pare

Boulogne-Billancourt, , France

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Centre Hospitalier Universitaire De Grenoble- Hopital Albert Michallon

La Tronche, , France

Site Status

Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez

Lille, , France

Site Status

Centre Leon-Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)

Lyon, , France

Site Status

Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu

Nantes, , France

Site Status

Centre Hospitalier Universitaire de Nice,Hopital l Archet

Nice, , France

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CIC Cochin Pasteur, Hopital Cochin

Paris, , France

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Hospital Saint-Louis - APHP

Paris, , France

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Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

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Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle

Rouen, , France

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Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP

Villejuif, , France

Site Status

NCT Dermatoonkologie -Hautklinik Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Site Status

Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR

Mainz, Rhineland-Palatinate, Germany

Site Status

Charite- Universitaetsmedizin Berlin

Berlin, , Germany

Site Status

Universitaetsklinikum der Ruhr Universitaet Bochum (UKRUB), St. Josef Hospital

Bochum, , Germany

Site Status

Elbekliniken Buxtehude

Buxtehude, , Germany

Site Status

Klinikum der Universitaet zu Koeln

Cologne, , Germany

Site Status

University Hospital Dresden

Dresden, , Germany

Site Status

Universitaetsklinikum Essen (AoR)

Essen, , Germany

Site Status

SLK-Kliniken Heilbronn GmbH

Heilbronn, , Germany

Site Status

Universitaetsklinikum Schleswig-Holstein, Campus Kiel

Kiel, , Germany

Site Status

LMU Munchen

München, , Germany

Site Status

University Hospital Tuebingen

Tübingen, , Germany

Site Status

University of Athens - Hospital of Venereology Dermatology Diseases Andreas Syggros

Athens, Attica, Greece

Site Status

Office of Dr. Aimilios Lallas MD

Thessaloniki, , Greece

Site Status

St. Vincent's University Hospital

Dublin, Leinster, Ireland

Site Status

University College Cork-Cork University Maternity Hospital

Cork, , Ireland

Site Status

University Hospital Galway

Galway, , Ireland

Site Status

ASST Papa Giovanni XXIII

Bergamo, , Italy

Site Status

Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna

Bologna, , Italy

Site Status

ASST Spedali Civili Brescia

Brescia, , Italy

Site Status

University of Brescia

Brescia, , Italy

Site Status

Universita di Firenze - Azienda Sanitaria Firenze

Florence, , Italy

Site Status

University L'Aquila

L’Aquila, , Italy

Site Status

IRCCS-Istituto Europeo di Oncologia

Milan, , Italy

Site Status

UOC Oncoematologia AOU Luigi Vanvitelli

Naples, , Italy

Site Status

U.O.S.C Di Oncologia Medica E Terapie Innovative

Napoli, , Italy

Site Status

A. Gemelli University Hospital, Catholic University of the Sacred Heart

Rome, , Italy

Site Status

IRCCS Istituto Clinico Humanitas

Rozzano, , Italy

Site Status

AOU Citta della Salute e della Scienza di Torino

Torino, , Italy

Site Status

Sapporo Medical University Hospital

Sapporo, Hokkaido, Japan

Site Status

Shizuoka Cancer Center - Oncology

Nagaizumi-Cho, Shizuoka, Japan

Site Status

National Cancer Center Hospital - Gastrointestinal Oncology

Chuo-ku, Tokyo, Japan

Site Status

Niigata Cancer Center Hospital

Niigata, , Japan

Site Status

Osaka International Cancer Institute - Clinical Oncology

Osaka, , Japan

Site Status

Regeneron Study Site

Auckland, , New Zealand

Site Status

Palmerston North Hospital

Palmerston North, , New Zealand

Site Status

Narodowy Instytut Onkologii im. Marii Sk¿odowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach

Gliwice, , Poland

Site Status

Regeneron Study Site

Krakow, , Poland

Site Status

Regeneron Study Site

Poznan, , Poland

Site Status

Regeneron Study Site

Warsaw, , Poland

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Site Status

State Healthcare Institution Oncology Dispensary 2 Ministry of Healthcare of Krasnodar Region

Sochi, Krasnodarskiy Kray, Russia

Site Status

SBHI of Stavropol Region Pyatigorsk Interdistrict Oncology Dispensary

Pyatigorsk, Stavropol Kray, Russia

Site Status

Regeneron Study Site

Magnitogorsk, , Russia

Site Status

N.N.Blokhin Cancer Research Center

Moscow, , Russia

Site Status

Regeneron Research Site

Omsk, , Russia

Site Status

Federal State Budgetary Institution Rostov Research Institute of Oncology of the Ministry of Healthcare of the Russian Federation

Rostov-on-Don, , Russia

Site Status

Regeneron Study Site

Saint Petersburg, , Russia

Site Status

Hospital Universitari Vall d'Hebron

Barcelona, Catalonia, Spain

Site Status

Hospital Universitario Fundacion Alcorcon

Alcorcón, Madrid, Spain

Site Status

Hospital Universitario de Torrejon

Torrejón de Ardoz, Madrid, Spain

Site Status

Catalan institute of Oncology Badalona

Badalona, , Spain

Site Status

Hospital Clinic de Barcelona - Institut Clinic de Malalties Hematologiques i Oncologiques (ICMHO)

Barcelona, , Spain

Site Status

Genesis Care hospital San Francisco de Asis

Madrid, , Spain

Site Status

Hospital General Universitario Gregorio Maranon (HGUGM)

Madrid, , Spain

Site Status

Clinica Universidad de Navarra

Madrid, , Spain

Site Status

Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, , Spain

Site Status

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status

Hospital Universitario Virgen Macarena-merge

Seville, , Spain

Site Status

Instituto Valenciano de Oncología

Valencia, , Spain

Site Status

Hospital Universitario y Politecnico La Fe-merge

Valencia, , Spain

Site Status

Derriford Hospital

Plymouth, Devon, United Kingdom

Site Status

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre (BHOC) - Bristol Cancer Institute

Bristol, Somerset, United Kingdom

Site Status

Velindre NHS Trust, Velindre Cancer Centre

Cardiff, , United Kingdom

Site Status

The Lothian University Hospitals NHS Lothian - Western General Hospital (WGH)

Edinburgh, , United Kingdom

Site Status

Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board

Glasgow, , United Kingdom

Site Status

St George's Hospital - St George's University Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

The Christie - The Christie NHS Foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Belgium Brazil Canada France Germany Greece Ireland Italy Japan New Zealand Poland Russia Spain United Kingdom

References

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Rischin D, Porceddu S, Day F, Brungs DP, Christie H, Jackson JE, Stein BN, Su YB, Ladwa R, Adams G, Bowyer SE, Otty Z, Yamazaki N, Bossi P, Challapalli A, Hauschild A, Lim AM, Patel VA, Walker JL, De Liz Vassen Schurmann M, Queirolo P, Canueto J, Ferreira da Silva FA, Stratigos A, Guminski A, Lin C, Damian F, Flatz L, Taylor AE, Carr DR, Harris S, Kirtbaya D, Quereux G, Rutkowski P, Basset-Seguin N, Khushalani NI, Robert C, Ju H, Joseph C, Bansal S, Chen CI, Seebach F, Yoo SY, Lowy I, Goncalves P, Fury MG; C-POST Trial Investigators. Adjuvant Cemiplimab or Placebo in High-Risk Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2025 Aug 21;393(8):774-785. doi: 10.1056/NEJMoa2502449. Epub 2025 May 31.

Reference Type DERIVED
PMID: 40454639 (View on PubMed)

Related Links

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Other Identifiers

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2019-000566-38

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-511653-22-00

Identifier Type: CTIS

Identifier Source: secondary_id

R2810-ONC-1788

Identifier Type: -

Identifier Source: org_study_id

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