Clinical trial NCT02760498: Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
Official title: A Phase 2 Study of REGN2810, a Fully Human Monoclonal Antibody to Programmed Death-1 (PD-1), in Patients With Advanced Cutaneous Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Advanced Cutaneous Squamous Cell Carcinoma
Keywords: Metastatic CSCC
Unresectable locally advanced CSCC
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-05-03
Enrollment: 432
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 goals of this study are to evaluate the clinical benefit and safety of cemiplimab in participants with metastatic (nodal or distant) Cutaneous Squamous Cell Carcinoma (CSCC), or unresectable locally advanced CSCC.


Eligibility criteria: Key Inclusion Criteria:

* At least 1 measurable lesion
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Adequate bone marrow function
* Adequate renal function
* Adequate hepatic function
* Archived or newly obtained tumor material
* Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6)
* Surgical or radiological treatment of lesions contraindicated

Key Exclusion Criteria:

* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events
* Prior treatment with an agent that blocks the PD-1/PD-L1pathway
* Prior treatment with a BRAF inhibitor
* Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
* Untreated brain metastasis(es) that may be considered active
* Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
* Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus
* History of non-infectious pneumonitis within the last 5 years
* Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
* Known allergy to doxycycline or tetracycline
* Patients with a history of solid organ transplant
* Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable

Other protocol-defined inclusion/exclusion criteria apply

Primary outcomes:
measure: Overall Response Rate (ORR) by Independent Central Review
timeFrame: Up to 108 weeks
Secondary outcomes:
measure: ORR by Investigator Assessment
timeFrame: Up to 108 weeks
measure: Duration of Response (DOR) by Independent Central Review
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: DOR by Investigator Assessment
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: Progression-Free Survival (PFS) by Independent Central Review
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: PFS by Investigator Assessment
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: Overall Survival (OS)
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: Complete Response (CR) Rate by Independent Central Review
timeFrame: Up to 108 weeks
measure: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Score
timeFrame: Baseline, Up to Cycle 12 Day 1 (Week 89)
measure: Number of Participants With Any Treatment Emergent Adverse Event (TEAE)
timeFrame: Up to 108 weeks plus 105 days (5 half-lives)
measure: Peak Concentration (Cmax) of Cemiplimab
timeFrame: Up to approximately 43 months
measure: Trough Concentration (Ctrough) of Cemiplimab
timeFrame: Up to approximately 43 months
measure: Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies
timeFrame: Up to approximately 43 months
measure: ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays
timeFrame: Up to 108 weeks
measure: DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
measure: PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays
timeFrame: Up to approximately 65 months (treatment period + follow-up including survival follow-up)
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Duarte
country: United States
facility: City of Hope Hospital
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Redwood City
country: United States
facility: Stanford University
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Aurora
country: United States
facility: University of Colorado, Denver
state: Colorado
city: Miami Beach
country: United States
facility: Mount Sinai Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
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
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
city: Omaha
country: United States
facility: Nebraska Methodist Hospital
state: Nebraska
city: New York
country: United States
facility: New York University
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Easton
country: United States
facility: St. Luke's Hematology Oncology Specialists
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Dermatology and Laser Center of Charleston
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Gosford
country: Australia
facility: Gosford Hospital
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane & Women's Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Kurralta Park
country: Australia
facility: Adelaide Cancer Centre
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Wodonga
country: Australia
facility: Border Medical Oncology
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
city: Ipatinga
country: Brazil
facility: Fundação São Francisco Xavier-Hospital Márcio Cunha
city: Lages
country: Brazil
facility: Animi
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de São Paulo ICESP
city: São Paulo
country: Brazil
facility: Fundação Antônio Prudente - AC Camargo Câncer Center
city: Lille
country: France
facility: Hôpital Claude Huriez
state: Nord
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bordeaux
country: France
facility: Hôpital Saint-André
city: Dijon
country: France
facility: CHU Dijon Bourgogne
city: Grenoble
country: France
facility: CHRU Grenoble
city: Marseille
country: France
facility: Hopitaux de La Timone
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hôpital Saint Louis
city: Pierre Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen
state: Baden-Württemberg
city: Munich
country: Germany
facility: LMU Klinikum der Universität München
state: Bayern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Essen
country: Germany
facility: Universitätsklinikum Essen
state: Nordrhein-Westfalen
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus
state: Sachsen
city: Kiel
country: Germany
facility: Universitatsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Charitè Campus Mitte
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera
city: Athens
country: Greece
facility: Andreas Sygros Hosptial-University of Athen
city: Napoli
country: Italy
facility: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
state: Campania
city: Padova
country: Italy
facility: Istituto Oncologico Veneto - I.R.C.C.S.
state: Veneto
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
city: L'Aquila
country: Italy
facility: Ospedale San Salvatore
city: Milan
country: Italy
facility: Istituto Europeo Di Oncologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
city: L'Hospitalet de Llobregat
country: Spain
facility: ICO l'Hospitalet - Hospital Duran i Reynals
state: Barelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
state: Cataluna
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitario Germans Trias i Pujol
city: Cordoba
country: Spain
facility: C.H. Regional Reina Sofia - PPDS
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncología
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References:
citation: Rischin D, Khushalani NI, Schmults CD, Guminski A, Chang ALS, Lewis KD, Lim AM, Hernandez-Aya L, Hughes BGM, Schadendorf D, Hauschild A, Thai AA, Stankevich E, Booth J, Yoo SY, Li S, Chen Z, Okoye E, Chen CI, Mastey V, Sasane M, Lowy I, Fury MG, Migden MR. Integrated analysis of a phase 2 study of cemiplimab in advanced cutaneous squamous cell carcinoma: extended follow-up of outcomes and quality of life analysis. J Immunother Cancer. 2021 Aug;9(8):e002757. doi: 10.1136/jitc-2021-002757.
citation: Paccaly AJ, Migden MR, Papadopoulos KP, Yang F, Davis JD, Rippley RK, Lowy I, Fury MG, Stankevich E, Rischin D. Fixed Dose of Cemiplimab in Patients with Advanced Malignancies Based on Population Pharmacokinetic Analysis. Adv Ther. 2021 May;38(5):2365-2378. doi: 10.1007/s12325-021-01638-5. Epub 2021 Mar 25.
citation: Rischin D, Migden MR, Lim AM, Schmults CD, Khushalani NI, Hughes BGM, Schadendorf D, Dunn LA, Hernandez-Aya L, Chang ALS, Modi B, Hauschild A, Ulrich C, Eigentler T, Stein B, Pavlick AC, Geiger JL, Gutzmer R, Alam M, Okoye E, Mathias M, Jankovic V, Stankevich E, Booth J, Li S, Lowy I, Fury MG, Guminski A. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing. J Immunother Cancer. 2020 Jun;8(1):e000775. doi: 10.1136/jitc-2020-000775.
citation: Migden MR, Khushalani NI, Chang ALS, Lewis KD, Schmults CD, Hernandez-Aya L, Meier F, Schadendorf D, Guminski A, Hauschild A, Wong DJ, Daniels GA, Berking C, Jankovic V, Stankevich E, Booth J, Li S, Weinreich DM, Yancopoulos GD, Lowy I, Fury MG, Rischin D. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020 Feb;21(2):294-305. doi: 10.1016/S1470-2045(19)30728-4. Epub 2020 Jan 14.
citation: Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS, Rabinowits G, Thai AA, Dunn LA, Hughes BGM, Khushalani NI, Modi B, Schadendorf D, Gao B, Seebach F, Li S, Li J, Mathias M, Booth J, Mohan K, Stankevich E, Babiker HM, Brana I, Gil-Martin M, Homsi J, Johnson ML, Moreno V, Niu J, Owonikoko TK, Papadopoulos KP, Yancopoulos GD, Lowy I, Fury MG. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018 Jul 26;379(4):341-351. doi: 10.1056/NEJMoa1805131. Epub 2018 Jun 4.