Clinical trial NCT03969004: Study of Adjuvant Cemiplimab Versus Placebo After Surgery and Radiation Therapy in Patients With High Risk Cutaneous Squamous Cell Carcinoma
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Cutaneous Squamous Cell Carcinoma
Keywords: High risk
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2019-05-31
Enrollment: 415
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause.
timeFrame: Up to 54 months
Secondary outcomes:
measure: 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.
timeFrame: Up to 78 months
measure: 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.
timeFrame: Up to 54 months
measure: 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.
timeFrame: Up to 54 months
measure: 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.
timeFrame: Up to 54 months
measure: Incidence and severity of treatment-emergent adverse events (TEAE)
timeFrame: Up to 78 months
measure: Incidence of deaths
timeFrame: Up to 78 months
measure: Incidence of laboratory abnormalities
timeFrame: Up to 78 months
measure: Cemiplimab concentrations in serum
timeFrame: Up to 78 months
measure: Anti-drug antibodies (ADA) in serum
timeFrame: Up to 78 months
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Tucson
country: United States
facility: Regeneron Study Site
state: Arizona
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: Los Angeles
country: United States
facility: University of Southern California (USC)
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute, Stanford Medicine at Stanford University
state: California
city: San Francisco
country: United States
facility: University Of California San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
state: California
city: Washington
country: United States
facility: George Washington University School of Medicine and Health Sciences
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Tampa
country: United States
facility: University of South Florida (USF) - H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Regeneron Study Site
state: Georgia
city: Chicago
country: United States
facility: Regeneron Study Site
state: Illinois
city: Louisville
country: United States
facility: Regeneron Study Site
state: Kentucky
city: Baltimore
country: United States
facility: Regeneron Study Site
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Cancer Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber/Harvard Cancer Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Medicine- University of Michigan
state: Michigan
city: Columbia
country: United States
facility: University of Missouri Health Care - University Physicians - Medicine Specialty Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in Saint Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: New Brunswick
country: United States
facility: Memorial Sloan Kettering
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering
state: New York
city: Cincinnati
country: United States
facility: Regeneron Research Site
state: Ohio
city: Gahanna
country: United States
facility: The Ohio State University
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Children's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Simmons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University Of Virginia Health System
state: Virginia
city: Albury
country: Australia
facility: The Border Cancer Hospital Dispensary - Albury Wodonga Regional Cancer Centre
state: New South Wales
city: Coffs Harbour
country: Australia
facility: Coffs Harbour Health Campus
state: New South Wales
city: Gosford
country: Australia
facility: Central Coast Cancer Centre-Gosford and Wyong Hospitals
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: North Shore Private Hospital
state: New South Wales
city: Wagga Wagga
country: Australia
facility: Cancer Care Associates (CCA) Riverina Cancer Care Centre (RCCC)
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Wollongong
country: Australia
facility: Illawarra Cancer Care Centre (ICCC)
state: New South Wales
city: Sydney
country: Australia
facility: Melanoma Institute
state: North South Wales
city: Bundaberg
country: Australia
facility: Wide Bay Hospital and Health Service - Cancer Care Services
state: Queensland
city: Cairns
country: Australia
facility: Cairns Hospital
state: Queensland
city: Herston
country: Australia
facility: The Royal Brisbane and Women's Hospital
state: Queensland
city: Southport
country: Australia
facility: ICON Cancer Care
state: Queensland
city: Toowoomba
country: Australia
facility: Toowoomba Hospital
state: Queensland
city: Tugun
country: Australia
facility: Genesis Care Tugun - John Flynn Private Hospital
state: Queensland
city: Urraween
country: Australia
facility: Wide Bay Hospital and Health Service - Cancer Care Services - Hervey Bay
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Ashford Cancer Centre Research-Adelaide Cancer Centre
state: South Australia
city: Hobart
country: Australia
facility: Royal Hobart Hospital-Hobart Hospital
state: Tasmania
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Bendigo
country: Australia
facility: Bendigo Health
state: Victoria
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Olivia Newton -John Cancer Wellness & Research Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre (PMCC)
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
city: Liverpool
country: Australia
facility: Liverpool Cancer Therapy Center
city: Liverpool
country: Australia
facility: University of New South Wales (UNSW) - Liverpool Hospital - Liverpool Cancer Therapy Centre
city: Townsville
country: Australia
facility: The Townsville Hospital and Health Service
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven Gasthuisberg Campus
state: Vlaams-Brabant
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Ipatinga
country: Brazil
facility: Fundacao Sao Francisco Xavier - Hospital Marcio Cunha (HMC) - Unidade I
state: Minas Gerais
city: Barretos
country: Brazil
facility: Fundacao Pio XII - Hospital de Cancer de Barretos
state: Porte Alegre
city: Santo Cristo
country: Brazil
facility: Instituto Nacional de Cancer Jose Alencar Gomes da Silva ¿ INCA
state: Rio De Janiero
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo (HSVP)
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa em Oncologia - Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da PUCRS
state: Rio Grande Do Sul
city: Itajai
country: Brazil
facility: Centro De Novos Tratamentos Itajai
state: Santa Catarina
city: Lajes
country: Brazil
facility: ANIMI
state: Santa Catarina
city: Mogi das Cruzes
country: Brazil
facility: Centro Oncologico Mogi das Cruzes
state: Sao Paulo
city: Ribeirao Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medician de Ribeirao Preto FMRP USP
state: Sao Paulo
city: Florianopolis
country: Brazil
facility: Ynova pesquisa clinica
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
city: Toronto
country: Canada
facility: University Health Network- Princess Margaret Cancer Center
state: Ontario
city: Dijon
country: France
facility: Centre Hospitalier Universitaire (CHU) de Dijon - Hopital du Bocage
state: Dijon Cedex
city: Bordeaux
country: France
facility: Hopital Saint Andre - CHU de Bordeaux
city: Boulogne Billancourt
country: France
facility: Hopital Ambroise Pare
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire De Grenoble- Hopital Albert Michallon
city: Lille
country: France
facility: Centre Hospitalier Regional Universitaire de Lille - Hopital Claude Huriez
city: Lyon
country: France
facility: Centre Leon-Berard (CLB) - Centre de Recherche en Cancerologie Lyon-Est (CRCL)
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes (CHU de Nantes) - Hopital Hotel Dieu
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice,Hopital l Archet
city: Paris Cedex 10
country: France
facility: Hospital Saint-Louis - APHP
city: Paris
country: France
facility: CIC Cochin Pasteur, Hopital Cochin
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon Sud
city: Rouen cedex
country: France
facility: Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy-Gustave Roussy Cancer Center -DITEP
city: Heidelberg
country: Germany
facility: NCT Dermatoonkologie -Hautklinik Heidelberg
state: Baden-Württemberg
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg Universitaet Mainz KoeR
state: Rheinland-Pfalz
city: Berlin
country: Germany
facility: Charite- Universitaetsmedizin Berlin
city: Bochum
country: Germany
facility: Universitaetsklinikum der Ruhr Universitaet Bochum (UKRUB), St. Josef Hospital
city: Buxtehude
country: Germany
facility: Elbekliniken Buxtehude
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Essen
country: Germany
facility: Universitaetsklinikum Essen (AoR)
city: Heilbronn
country: Germany
facility: SLK-Kliniken Heilbronn GmbH
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein, Campus Kiel
city: Koeln
country: Germany
facility: Klinikum der Universitaet zu Koeln
city: Muenchen
country: Germany
facility: LMU Munchen
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
city: Athens
country: Greece
facility: University of Athens - Hospital of Venereology Dermatology Diseases Andreas Syggros
state: Attiki
city: Thessaloniki
country: Greece
facility: Office of Dr. Aimilios Lallas MD
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
state: Leinster
city: Cork
country: Ireland
facility: University College Cork-Cork University Maternity Hospital
city: Galway
country: Ireland
facility: University Hospital Galway
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna
city: Brescia
country: Italy
facility: ASST Spedali Civili Brescia
city: Brescia
country: Italy
facility: University of Brescia
city: Firenze
country: Italy
facility: Universita di Firenze - Azienda Sanitaria Firenze
city: L'Aquila
country: Italy
facility: University L'Aquila
city: Milan
country: Italy
facility: IRCCS-Istituto Europeo di Oncologia
city: Naples
country: Italy
facility: UOC Oncoematologia AOU Luigi Vanvitelli
city: Napoli
country: Italy
facility: U.O.S.C Di Oncologia Medica E Terapie Innovative
city: Rome
country: Italy
facility: A. Gemelli University Hospital, Catholic University of the Sacred Heart
city: Rozzano
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino
city: Sapporo
country: Japan
facility: Sapporo Medical University Hospital
state: Hokkaido
city: Nagaizumi-Cho
country: Japan
facility: Shizuoka Cancer Center - Oncology
state: Shizuoka
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital - Gastrointestinal Oncology
state: Tokyo
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Osaka
country: Japan
facility: Osaka International Cancer Institute - Clinical Oncology
city: Auckland
country: New Zealand
facility: Regeneron Study Site
city: Palmerston North
country: New Zealand
facility: Palmerston North Hospital
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sk¿odowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach
city: Krakow
country: Poland
facility: Regeneron Study Site
city: Poznan
country: Poland
facility: Regeneron Study Site
city: Warsaw
country: Poland
facility: Regeneron Study Site
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
city: Sochi
country: Russian Federation
facility: State Healthcare Institution Oncology Dispensary 2 Ministry of Healthcare of Krasnodar Region
state: Krasnodar Krai
city: Pyatigorsk
country: Russian Federation
facility: SBHI of Stavropol Region Pyatigorsk Interdistrict Oncology Dispensary
state: Stavropol Region
city: Magnitogorsk
country: Russian Federation
facility: Regeneron Study Site
city: Moscow
country: Russian Federation
facility: N.N.Blokhin Cancer Research Center
city: Omsk
country: Russian Federation
facility: Regeneron Research Site
city: Rostov-Na-Donu
country: Russian Federation
facility: Federal State Budgetary Institution Rostov Research Institute of Oncology of the Ministry of Healthcare of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: Regeneron Study Site
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Cataluna
city: Alcorcon
country: Spain
facility: Hospital Universitario Fundacion Alcorcon
state: Madrid
city: Torrejon de Ardoz
country: Spain
facility: Hospital Universitario de Torrejon
state: Madrid
city: Badalona
country: Spain
facility: Catalan institute of Oncology Badalona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona - Institut Clinic de Malalties Hematologiques i Oncologiques (ICMHO)
city: Madrid
country: Spain
facility: Genesis Care hospital San Francisco de Asis
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon (HGUGM)
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre-Centro de Actividades Ambulatorias
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena-merge
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe-merge
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre (BHOC) - Bristol Cancer Institute
state: Somerset
city: Cardiff
country: United Kingdom
facility: Velindre NHS Trust, Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: The Lothian University Hospitals NHS Lothian - Western General Hospital (WGH)
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre - Greater Glasgow Health Board
city: London
country: United Kingdom
facility: St George's Hospital - St George's University Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie - The Christie NHS Foundation Trust
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: