Clinical trial NCT03132636: PD-1 in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy
Official title: A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1, in Patients With Advanced Basal Cell Carcinoma Who Experienced Progression of Disease on Hedgehog Pathway Inhibitor Therapy, or Were Intolerant of Prior Hedgehog Pathway Inhibitor Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Basal Cell
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-04-28
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective is to estimate the objective response rate (ORR) for metastatic Basal Cell Carcinoma (BCC) (group 1) and for unresectable locally advanced BCC (group 2) when treated with cemiplimab as a monotherapy


Eligibility criteria: Key Inclusion Criteria:

* Confirmed diagnosis of invasive BCC
* Progression of disease on hedgehog inhibitor (HHI) therapy or intolerance of prior HHI therapy
* At least 1 measurable lesion
* ≥18 years of age
* Hepatic function, renal function, bone marrow function in defined lab-value-ranges
* Anticipated life expectancy \>12 weeks
* Consent to provide archived tumor biopsy material (all patients)
* Group 2: consent to undergo research biopsies
* Group 2: must not be a candidate for radiation therapy or surgery
* Comply with study procedures and site visits
* Sign Subject Information Sheet and Informed Consent Form

Key Exclusion Criteria:

* Ongoing or recent significant autoimmune disease
* Prior treatment with specific pathway-blockers (PD-1/PD-L1)
* Prior treatment with immune-modulating agents within 28 days before cemiplimab
* Untreated brain metastasis that may be considered active
* Immunosuppressive corticosteroid doses (\>10mg prednisone) within 28 days prior to treatment with cemiplimab
* Active infections requiring therapy, including HIV, hepatitis
* Pneumonitis within the last 5 years
* Cancer treatment other than radiation therapy, including investigational or standard of care, within 30 days prior to treatment with cemiplimab
* Documented allergic reactions or similar to antibody treatments
* Concurrent malignancies other than BCC, other than those with negligible risk of metastases or death
* Any acute or chronic psychiatric problems
* Having received a solid organ transplantation
* Inability to undergo contrast radiological assessments
* Breastfeeding, pregnant, women of childbearing potential not using contraception

Note: Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Independent Central Review (ICR)
timeFrame: Up to 1422 days (approximately 46 months)
Secondary outcomes:
measure: Objective Response Rate (ORR) Per Investigator Assessment
timeFrame: Up to 1422 days (approximately 46 months)
measure: Duration of Response (DOR) as Assessed by ICR
timeFrame: Up to 48 months
measure: Duration of Response (DOR) Per Investigator Assessment
timeFrame: Up to 48 months
measure: Complete Response (CR) Rate as Assessed by ICR
timeFrame: Up to 48 months
measure: Complete Response (CR) Rate Per Investigator Assessment
timeFrame: Up to 48 months
measure: Progression Free Survival (PFS) as Assessed by ICR
timeFrame: Up to 60 months
measure: Progression Free Survival (PFS) Per Investigator Assessment
timeFrame: Up to 60 months
measure: Overall Survival (OS)
timeFrame: Up to 60 months
measure: Change From Baseline of Patient-reported Outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])
measure: Change From Baseline of Patient-reported Outcomes in Skindex-16 Questionnaire
timeFrame: Baseline (Day 1 of Cycle 1); Day 1 of Cycles 2 to 9 (Cycles 1-5 [Each cycle of 9 weeks], Cycles 6 to 9 [Each cycle of 12 weeks])
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Up to 1422 days (approximately 46 months)
measure: Serum Concentration at Pre-infusion (Ctrough)
timeFrame: At pre-infusion on Cycle 1 Day 22 and Cycle 3 Day 1 (Each cycle of 9 weeks)
measure: Serum Concentration at End of Infusion (Cmax)
timeFrame: At end-of-infusion (within 10 minutes after the end of infusion) on Cycle 1 Day 1 and Cycle 3 Day 1 (Each cycle of 9 weeks)
measure: Number of Participants With Anti-Drug Antibody (ADA) Status
timeFrame: Cycle 1: Days 1 and 43; Cycles 3 and 5: Day 1 (Each cycle of 9 weeks)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: The University of Arizona Cancer Centre at Dignity Health
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona - Mayo Clinic Hospital
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Redwood City
country: United States
facility: Stanford Medicine Outpatient Center - Stanford Dermatology Clinic-Stanford University School of Medicine
state: California
city: San Francisco
country: United States
facility: UCSF Helen Dillion Family Cancer Care Center
state: California
city: Denver
country: United States
facility: University of Colorado Hospital, Anschutz Outpatient Pavilion
state: Colorado
city: Miami
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern Medical Faculty Foundation
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute (DFCI)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Morristown
country: United States
facility: Atlantic Health System / Morristown Medical Center
state: New Jersey
city: Summit
country: United States
facility: Overlook Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University School Of Medicine, Kaplan Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute
state: Ohio
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Clinical Research Center of the Carolinas
state: South Carolina
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Graz
country: Austria
facility: LKH - Universitaetsklinikum Graz
state: Steiermark
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck, Universitaetsklinik fuer Dermatologie, Venerologie und Allergologie
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Odette Cancer Center-Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: London Regional Cancer Program, London Hsc
state: Ontario
city: Dijon
country: France
facility: CHU de Dijon - Hopital du Bocage
state: Cedex
city: Paris
country: France
facility: Hopital Saint Louis
state: Europe
city: Pierre Benite Cedex
country: France
facility: Centre Hospitalier Lyon-Sud -Hospices Civils de Lyon Groupement Hospitalier Sud
state: Paris
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire de Bordeaux - Groupe Hospitalier Saint-André - Hôpital Saint-André
city: Boulogne Billancourt
country: France
facility: Hopital Ambroise Pare
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Lille Cedex
country: France
facility: Hopital Huriez - CHRU de Lille
city: Lyon
country: France
facility: Centre Leon-Berard (CLB)
city: Nantes
country: France
facility: CHU Hotel Dieu
city: Rouen cedex
country: France
facility: Centre Hospitalier Universitaire de Rouen-Hopital Charles Nicolle
city: Toulouse Cedex
country: France
facility: Institut Claudius Regaud
city: Villejuif Cedex
country: France
facility: Institut Gustave Roussy
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
state: Hessen/Germany
city: Berlin
country: Germany
facility: Hauttumorcentrum der Charite (HTCC)-Charite Universitatsmedizin Berlin
city: Buxtehude
country: Germany
facility: Elbekliniken Buxtehude
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Essen
country: Germany
facility: Universitaetsklinik Essen
city: Gera
country: Germany
facility: SRH Wald-Kliniken Gera GmbH
city: Hannover
country: Germany
facility: Hannover Medical School
city: Heidelberg
country: Germany
facility: NCT Dermatoonkologie
city: Kiel
country: Germany
facility: University of Kiel
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Quedlinburg
country: Germany
facility: Klinik Fur Dermatologie Und Allergollogie
city: Tübingen
country: Germany
facility: University Hospital Tubingen
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens - School of Health Sciences - Faculty of Medicine
city: Athens
country: Greece
facility: National and Kapodistrian University of Athens - School of Health Sciences
city: Athens
country: Greece
facility: Andreas Sygros Hosptial-University of Athen
city: Ioánnina
country: Greece
facility: University General Hospital of Ioannina - Dermatology and Venereology Department
city: Bologna
country: Italy
facility: Policlinico S.Orsola-Malpighi U.O. Dermatologia - University of Bologna
state: Bo
city: Brescia
country: Italy
facility: Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia
state: Province Of Brescia
city: Firenze
country: Italy
facility: U.O.Dermatologia Azienda Sanitaria Firenze Universita' Firenze
city: L'Aquila
country: Italy
facility: University L'Aquila
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Napoli
country: Italy
facility: U.O.S.C Di Oncologia Medica E Terapie Innovative
city: Roma
country: Italy
facility: Catholic University of the S.Heart
city: Badalona
country: Spain
facility: Catalan Institute of Oncology Badalona
city: Barcelona
country: Spain
facility: Hospital Clinic I Provincialde Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario de Torrejon
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Zürich
country: Switzerland
facility: University Hospital Zurich Usz
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Stratigos AJ, Sekulic A, Peris K, Bechter O, Prey S, Kaatz M, Lewis KD, Basset-Seguin N, Chang ALS, Dalle S, Orland AF, Licitra L, Robert C, Ulrich C, Hauschild A, Migden MR, Dummer R, Li S, Yoo SY, Mohan K, Coates E, Jankovic V, Fiaschi N, Okoye E, Bassukas ID, Loquai C, De Giorgi V, Eroglu Z, Gutzmer R, Ulrich J, Puig S, Seebach F, Thurston G, Weinreich DM, Yancopoulos GD, Lowy I, Bowler T, Fury MG. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):848-857. doi: 10.1016/S1470-2045(21)00126-1. Epub 2021 May 14.
citation: Li R, Lee G, Huang M, El-Sherief A. Rare basal cell metastasis of a basal-squamous skin collision tumour to the lung and axillary lymph node. BMJ Case Rep. 2019 Oct 3;12(10):e231487. doi: 10.1136/bcr-2019-231487.