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

Cutaneous Squamous Cell Carcinoma Clinical Trial

Official title:

A Randomized, Placebo-Controlled, Double-Blind Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03969004
• Other study ID #: R2810-ONC-1788
• Secondary ID: 2019-000566-38
• Status: Recruiting
• Phase: Phase 3
• Start date: June 4, 2019
• Est. completion date: January 28, 2028

Study information

• Verified date: January 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 412
• Est. completion date: January 28, 2028
• Est. primary completion date: May 19, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria apply

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Cutaneous Squamous Cell Carcinoma

Intervention

Drug:
• Cemiplimab
Intravenous (IV) infusion over 30 minutes
• Placebo
Intravenous (IV) infusion over 30 minutes

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide
Australia	The Border Cancer Hospital Dispensary - Albury Wodonga Regional Cancer Centre	Albury	New South Wales
Australia	Bendigo Health	Bendigo	Victoria
Australia	Wide Bay Hospital and Health Service - Cancer Care Services	Bundaberg	Queensland
Australia	Cairns Hospital	Cairns	Queensland
Australia	Coffs Harbour Health Campus	Coffs Harbour	New South Wales
Australia	St. Vincent's Hospital	Fitzroy	Victoria
Australia	Central Coast Cancer Centre-Gosford and Wyong Hospitals	Gosford	New South Wales
Australia	Olivia Newton -John Cancer Wellness & Research Centre	Heidelberg	Victoria
Australia	The Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Hobart Hospital	Hobart	Tasmania
Australia	Royal Hobart Hospital-Hobart Hospital	Hobart	Tasmania
Australia	St George Hospital	Kogarah	New South Wales
Australia	Ashford Cancer Centre Research-Adelaide Cancer Centre	Kurralta Park	South Australia
Australia	Liverpool Cancer Therapy Center	Liverpool
Australia	University of New South Wales (UNSW) - Liverpool Hospital - Liverpool Cancer Therapy Centre	Liverpool
Australia	Peter Maccallum Cancer Centre (PMCC)	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	ICON Cancer Care	Southport	Queensland
Australia	North Shore Private Hospital	St Leonards	New South Wales
Australia	Melanoma Institute	Sydney	North South Wales
Australia	Toowoomba Hospital	Toowoomba	Queensland
Australia	The Townsville Hospital and Health Service	Townsville
Australia	Genesis Care Tugun - John Flynn Private Hospital	Tugun	Queensland
Australia	Wide Bay Hospital and Health Service - Cancer Care Services - Hervey Bay	Urraween	Queensland
Australia	Cancer Care Associates (CCA) Riverina Cancer Care Centre (RCCC)	Wagga Wagga	New South Wales
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Illawarra Cancer Care Centre (ICCC)	Wollongong	New South Wales
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Belgium	Cliniques Universitaires Saint-Luc	Bruxelles
Belgium	Universitair Ziekenhuis Leuven Gasthuisberg Campus	Leuven	Vlaams-Brabant
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos	Barretos	Porte Alegre
Brazil	Ynova pesquisa clinica	Florianopolis
Brazil	Fundacao Sao Francisco Xavier - Hospital Marcio Cunha (HMC) - Unidade I	Ipatinga	Minas Gerais
Brazil	Centro De Novos Tratamentos Itajai	Itajai	Santa Catarina
Brazil	ANIMI	Lajes	Santa Catarina
Brazil	Centro Oncologico Mogi das Cruzes	Mogi das Cruzes	Sao Paulo
Brazil	Hospital Sao Vicente de Paulo (HSVP)	Passo Fundo	Rio Grande Do Sul
Brazil	Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clinicas da Faculdade de Medician de Ribeirao Preto FMRP USP	Ribeirao Preto	Sao Paulo
Brazil	Instituto Nacional de Cancer Jose Alencar Gomes da Silva ¿ INCA	Santo Cristo	Rio De Janiero
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo
Canada	University Health Network- Princess Margaret Cancer Center	Toronto	Ontario
France	Hopital Saint Andre - CHU de Bordeaux	Bordeaux
France	Hopital Ambroise Pare	Boulogne Billancourt
France	Centre Hospitalier Universitaire (CHU) de Dijon - Hopital du Bocage	Dijon	Dijon Cedex
France	Centre Hospitalier Universitaire De Grenoble- Hopital Albert Michallon	La Tronche
France	Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez	Lille
France	Centre Leon-Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)	Lyon
France	Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu	Nantes
France	Centre Hospitalier Universitaire de Nice,Hopital l Archet	Nice
France	CIC Cochin Pasteur, Hopital Cochin	Paris
France	Hospital Saint-Louis - APHP	Paris Cedex 10
France	Centre Hospitalier Lyon Sud	Pierre Benite Cedex
France	Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle	Rouen cedex
France	Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP	Villejuif Cedex
Germany	Charite- Universitaetsmedizin Berlin	Berlin
Germany	Universitaetsklinikum der Ruhr Universitaet Bochum (UKRUB), St. Josef Hospital	Bochum
Germany	Elbekliniken Buxtehude	Buxtehude
Germany	University Hospital Dresden	Dresden
Germany	Universitaetsklinikum Essen (AoR)	Essen
Germany	NCT Dermatoonkologie -Hautklinik Heidelberg	Heidelberg	Baden-Württemberg
Germany	SLK-Kliniken Heilbronn GmbH	Heilbronn
Germany	Universitaetsklinikum Schleswig-Holstein, Campus Kiel	Kiel
Germany	Klinikum der Universitaet zu Koeln	Koeln
Germany	Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR	Mainz	Rheinland-Pfalz
Germany	LMU Munchen	Muenchen
Germany	University Hospital Tuebingen	Tuebingen
Greece	University of Athens - Hospital of Venereology Dermatology Diseases Andreas Syggros	Athens	Attiki
Greece	Office of Dr. Aimilios Lallas MD	Thessaloniki
Ireland	University College Cork-Cork University Maternity Hospital	Cork
Ireland	St. Vincent's University Hospital	Dublin	Leinster
Ireland	University Hospital Galway	Galway
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna	Bologna
Italy	ASST Spedali Civili Brescia	Brescia
Italy	University of Brescia	Brescia
Italy	Universita di Firenze - Azienda Sanitaria Firenze	Firenze
Italy	University L'Aquila	L'Aquila
Italy	IRCCS-Istituto Europeo di Oncologia	Milan
Italy	UOC Oncoematologia AOU Luigi Vanvitelli	Naples
Italy	U.O.S.C Di Oncologia Medica E Terapie Innovative	Napoli
Italy	A. Gemelli University Hospital, Catholic University of the Sacred Heart	Rome
Italy	IRCCS Istituto Clinico Humanitas	Rozzano
Italy	AOU Citta della Salute e della Scienza di Torino	Torino
Japan	National Cancer Center Hospital - Gastrointestinal Oncology	Chuo-ku	Tokyo
Japan	Shizuoka Cancer Center - Oncology	Nagaizumi-Cho	Shizuoka
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Osaka International Cancer Institute - Clinical Oncology	Osaka
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
New Zealand	Regeneron Study Site	Auckland
New Zealand	Palmerston North Hospital	Palmerston North
Poland	Narodowy Instytut Onkologii im. Marii Sk¿odowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach	Gliwice
Poland	Regeneron Study Site	Krakow
Poland	Regeneron Study Site	Poznan
Poland	Regeneron Study Site	Warsaw
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warszawa
Russian Federation	Regeneron Study Site	Magnitogorsk
Russian Federation	N.N.Blokhin Cancer Research Center	Moscow
Russian Federation	Regeneron Research Site	Omsk
Russian Federation	SBHI of Stavropol Region Pyatigorsk Interdistrict Oncology Dispensary	Pyatigorsk	Stavropol Region
Russian Federation	Federal State Budgetary Institution Rostov Research Institute of Oncology of the Ministry of Healthcare of the Russian Federation	Rostov-Na-Donu
Russian Federation	Regeneron Study Site	Saint Petersburg
Russian Federation	State Healthcare Institution Oncology Dispensary 2 Ministry of Healthcare of Krasnodar Region	Sochi	Krasnodar Krai
Spain	Hospital Universitario Fundacion Alcorcon	Alcorcon	Madrid
Spain	Catalan institute of Oncology Badalona	Badalona
Spain	Hospital Clinic de Barcelona - Institut Clinic de Malalties Hematologiques i Oncologiques (ICMHO)	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona	Cataluna
Spain	Clinica Universidad de Navarra	Madrid
Spain	Genesis Care hospital San Francisco de Asis	Madrid
Spain	Hospital General Universitario Gregorio Maranon (HGUGM)	Madrid
Spain	Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen Macarena-merge	Sevilla
Spain	Hospital Universitario de Torrejon	Torrejon de Ardoz	Madrid
Spain	Hospital Universitario y Politecnico La Fe-merge	Valencia
Spain	Instituto Valenciano de Oncología	Valencia
United Kingdom	University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre (BHOC) - Bristol Cancer Institute	Bristol	Somerset
United Kingdom	Velindre NHS Trust, Velindre Cancer Centre	Cardiff
United Kingdom	The Lothian University Hospitals NHS Lothian - Western General Hospital (WGH)	Edinburgh
United Kingdom	Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board	Glasgow
United Kingdom	St George's Hospital - St George's University Hospitals NHS Foundation Trust	London
United Kingdom	The Christie - The Christie NHS Foundation Trust	Manchester
United Kingdom	Derriford Hospital	Plymouth	Devon
United States	Michigan Medicine- University of Michigan	Ann Arbor	Michigan
United States	Regeneron Study Site	Atlanta	Georgia
United States	Regeneron Study Site	Baltimore	Maryland
United States	Memorial Sloan Kettering	Basking Ridge	New Jersey
United States	Dana Farber/Harvard Cancer Center	Boston	Massachusetts
United States	Massachusetts General Cancer Center	Boston	Massachusetts
United States	University Of Virginia Health System	Charlottesville	Virginia
United States	Regeneron Study Site	Chicago	Illinois
United States	Regeneron Research Site	Cincinnati	Ohio
United States	University of Missouri Health Care - University Physicians - Medicine Specialty Clinic	Columbia	Missouri
United States	Memorial Sloan Kettering	Commack	New York
United States	Texas Oncology - Baylor Charles A. Simmons Cancer Center	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	The Ohio State University	Gahanna	Ohio
United States	University of Florida Health	Gainesville	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Memorial Sloan Kettering	Harrison	New York
United States	Penn State Hershey Children's Hospital	Hershey	Pennsylvania
United States	The Angeles Clinic	Los Angeles	California
United States	University of Southern California (USC)	Los Angeles	California
United States	Regeneron Study Site	Louisville	Kentucky
United States	Miami Cancer Institute at Baptist Health, Inc.	Miami	Florida
United States	Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering	Middletown	New Jersey
United States	Memorial Sloan Kettering	Montvale	New Jersey
United States	Sarah Cannon Research Institute - Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering	New Brunswick	New Jersey
United States	Columbia University	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Nebraska Methodist Hospital	Omaha	Nebraska
United States	Stanford Cancer Institute, Stanford Medicine at Stanford University	Palo Alto	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Washington University in Saint Louis	Saint Louis	Missouri
United States	University Of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center	San Francisco	California
United States	University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Regeneron Study Site	Tucson	Arizona
United States	Memorial Sloan Kettering	Uniondale	New York
United States	George Washington University School of Medicine and Health Sciences	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause.	For patients who do not have a tumor recurrence or death, DFS will be censored on the date of last disease assessment.	Up to 54 months
Secondary	Overall survival (OS), defined as time from randomization to the date of death. A patient who has not died will be censored on the last known date as alive.		Up to 78 months
Secondary	FFLRR defined as time from randomization to the date of first locoregional recurrence (LRR). Patients who died without a preceding LRR will be censored on the date of death.	For patients who do not have a LRR or death, FFLRR will be censored on the date of last disease assessment.	Up to 54 months
Secondary	Freedom from distant recurrence (FFDR), defined as time from randomization to the date of first distant recurrence (DR). Patients who died without a preceding DR will be censored on the date of death.	For patients who do not have a DR or death, FFDR will be censored on the date of last disease assessment.	Up to 54 months
Secondary	Cumulative occurrence of second primary cutaneous squamous cell carcinoma tumor (SPTs) for each patient from randomization to occurrence of first primary endpoint event or end of study.		Up to 54 months
Secondary	Incidence and severity of treatment-emergent adverse events (TEAE)		Up to 78 months
Secondary	Incidence of deaths		Up to 78 months
Secondary	Incidence of laboratory abnormalities		Up to 78 months
Secondary	Cemiplimab concentrations in serum		Up to 78 months
Secondary	Anti-drug antibodies (ADA) in serum		Up to 78 months

External Links

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