Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
- Registration Number
- NCT02760498
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
Groups 1 to 4 To estimate the clinical benefit of cemiplimab monotherapy for patients with: metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC
Group 6 To provide additional efficacy and safety data for cemiplimab monotherapy in patients with advanced CSCC (metastatic \[nodal or distant\] or locally advanced treated with cemiplimab
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 432
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 3 cemiplimab Patients with metastatic CSCC to distant sites or lymph nodes. Cemiplimab administered IV Q3 weeks. Group 1 cemiplimab Patients with metastatic CSCC: to distant sites or lymph nodes. Cemiplimab administered intravenously (IV) every 2 weeks (Q2W). Group 6 cemiplimab Patients with advanced CSCC (metastatic \[nodal or distant\] or locally advanced) who received cemiplimab IV Q3W for at least 27 weeks without experiencing disease progression, will have the option to receive cemiplimab by subcutaneous (SC) injection Q3W (first 12 patients) or Q6W (next ≥ 6 patients) basis. Group 4 cemiplimab Patients with advanced CSCC \[metastatic (nodal or distal) or unresectable locally advanced\] Cemplimab administered IV Q4 weeks. Group 2 cemiplimab Patients with unresectable locally advanced CSCC. Cemiplimab administered IV Q2 weeks.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) by Independent Central Review Up to 108 weeks ORR was defined as percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). For participants with metastatic disease, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 millimeter (mm) \<1 (centimeter (cm). -PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
- Secondary Outcome Measures
Name Time Method ORR by Investigator Assessment Up to 108 weeks ORR was defined as percentage of participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm \<1 cm. -PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
Duration of Response (DOR) by Independent Central Review Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria were first met for CR/PR, whichever was recorded first, until the first date of recurrent or Progressive Disease (PD) or death due to any cause in participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
DOR by Investigator Assessment Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria were first met for CR/PR, as defined in Outcome Measure 1, whichever was recorded first, until the first date of recurrent or Progressive Disease (PD) or death due to any cause in participants with BOR of CR or PR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (World Health Organization (WHO) criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Progression-Free Survival (PFS) by Independent Central Review Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from start of treatment until the first date of recurrent or PD, or death due to any cause. For participants with metastatic disease, RECIST v1.1 was used to determine PD. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
PFS by Investigator Assessment Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from start of treatment until the first date of recurrent or PD, or death due to any cause. For participants with metastatic disease, RECIST v1.1 was used to determine PD. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -PD: At least a 20% increase in the sum of the diameters of target lesions with the sum demonstrating an absolute increase of at least 5 mm (0.5 cm), or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Clinical Response Criteria: -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Overall Survival (OS) Up to approximately 65 months (treatment period + follow-up including survival follow-up) OS was measured from start of treatment until death due to any cause.
Complete Response (CR) Rate by Independent Central Review Up to 108 weeks CR rate was defined as percentage of participants with BOR of CR. For participants with metastatic disease, RECIST v1.1 was used to determine BOR. For participants with unresectable locally advanced disease, clinical response criteria were used. RECIST v1.1 Criteria: -CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm \<1 cm. Clinical Response Criteria: -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions.
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 Baseline, Up to Cycle 12 Day 1 (Week 89) EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. Items contributing to the GHS/QoL, were scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that transformed score lies between 0 to 100. A higher score indicates better global health status/functioning and a negative change from baseline indicated less improvement.
DOR by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to approximately 65 months (treatment period + follow-up including survival follow-up) DOR was measured from the time measurement criteria are first met for CR/PR, as defined in Outcome Measure 13, whichever was recorded first, until the first date of recurrent or PD or death due to any cause in participants with BOR of CR or PR. Expression level of PD-L1 was assessed in tumor biopsy samples by IHC. -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Number of Participants With Any Treatment Emergent Adverse Event (TEAE) Up to 108 weeks plus 105 days (5 half-lives) An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. Treatment-emergent adverse events (TEAEs) are defined as those not present at baseline or represent the exacerbation of a condition present at baseline during the on-treatment period or follow-up period. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
Peak Concentration (Cmax) of Cemiplimab Up to approximately 43 months Trough Concentration (Ctrough) of Cemiplimab Up to approximately 43 months Number of Participants With Treatment-Emergent Anti-cemiplimab Antibodies Up to approximately 43 months ORR by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to 108 weeks ORR was defined as percentage of participants with BOR of CR or PR. Expression level of PD-L1 was assessed in tumor biopsy samples by immunohistochemistry (IHC). -CR: All target and nontarget lesion(s) no longer visible, maintained for at least 4 weeks and no new lesions. -PR: Decrease of at least 50% in the sum the products of perpendicular longest dimensions of target lesion(s), maintained for at least 4 weeks and no new lesions.
PFS by Independent Central Review for Participants With Evaluable PD-L1 Assays Up to approximately 65 months (treatment period + follow-up including survival follow-up) PFS was measured from time of enrollment until the first date of recurrent or progressive disease, or death due to any cause. Expression level of PD-L1 was assessed in tumor biopsy samples. -PD: increase of ≥ 25% (WHO criteria) in the sum of the products of perpendicular longest dimensions of target lesion(s) and/or the appearance of new lesions.
Trial Locations
- Locations (78)
Stanford University
🇺🇸Redwood City, California, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
University of Arizona Cancer Center
🇺🇸Phoenix, Arizona, United States
University of California, Los Angeles
🇺🇸Los Angeles, California, United States
CHU Dijon Bourgogne
🇫🇷Dijon, France
H. Lee Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
Mount Sinai Comprehensive Cancer Center
🇺🇸Miami Beach, Florida, United States
Hôpital Saint-André
🇫🇷Bordeaux, France
Hopitaux de La Timone
🇫🇷Marseille, France
Istituto Europeo Di Oncologia
🇮🇹Milan, Italy
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
Hôpital Claude Huriez
🇫🇷Lille, Nord, France
Hopital Avicenne
🇫🇷Bobigny, France
Universitätsklinikum Tübingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Animi
🇧🇷Lages, Brazil
City of Hope Hospital
🇺🇸Duarte, California, United States
University of California, San Diego
🇺🇸San Diego, California, United States
University of Colorado, Denver
🇺🇸Aurora, Colorado, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Nebraska Methodist Hospital
🇺🇸Omaha, Nebraska, United States
New York University
🇺🇸New York, New York, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Rochester Medical Center
🇺🇸Rochester, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Dermatology and Laser Center of Charleston
🇺🇸Charleston, South Carolina, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Canberra Hospital
🇦🇺Garran, Australian Capital Territory, Australia
Royal Brisbane & Women's Hospital
🇦🇺Herston, Queensland, Australia
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Princess Alexandra Hospital
🇦🇺Woolloongabba, Queensland, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Border Medical Oncology
🇦🇺Wodonga, Victoria, Australia
Fundação São Francisco Xavier-Hospital Márcio Cunha
🇧🇷Ipatinga, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner
🇧🇷Curitiba, Brazil
Centre Hospitalier Universitaire de Nantes
🇫🇷Nantes, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Bénite, France
Hôpital Saint Louis
🇫🇷Paris, France
Hopital Cochin
🇫🇷Paris, France
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Universitätsklinikum Carl Gustav Carus
🇩🇪Dresden, Sachsen, Germany
LMU Klinikum der Universität München
🇩🇪Munich, Bayern, Germany
Universitätsklinikum Essen
🇩🇪Essen, Nordrhein-Westfalen, Germany
Charitè Campus Mitte
🇩🇪Berlin, Germany
Universitatsklinikum Schleswig-Holstein
🇩🇪Kiel, Schleswig-Holstein, Germany
SRH Wald-Klinikum Gera
🇩🇪Gera, Germany
Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale
🇮🇹Napoli, Campania, Italy
Andreas Sygros Hosptial-University of Athen
🇬🇷Athens, Greece
Istituto Oncologico Veneto - I.R.C.C.S.
🇮🇹Padova, Veneto, Italy
ASST degli Spedali Civili di Brescia - Spedali Civili di Brescia
🇮🇹Brescia, Italy
Fondazione Policlinico Universitario A Gemelli
🇮🇹Roma, Italy
Ospedale San Salvatore
🇮🇹L'Aquila, Italy
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Barelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario Germans Trias i Pujol
🇪🇸Barcelona, Spain
C.H. Regional Reina Sofia - PPDS
🇪🇸Cordoba, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Marques de Valdecilla
🇪🇸Santander, Spain
Fundacion Instituto Valenciano de Oncología
🇪🇸Valencia, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
St. Luke's Hematology Oncology Specialists
🇺🇸Easton, Pennsylvania, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Washington University in St. Louis
🇺🇸Saint Louis, Missouri, United States
Adelaide Cancer Centre
🇦🇺Kurralta Park, South Australia, Australia
Gosford Hospital
🇦🇺Gosford, New South Wales, Australia
Calvary Mater Newcastle
🇦🇺Waratah, New South Wales, Australia
Instituto do Cancer do Estado de São Paulo ICESP
🇧🇷Sao Paulo, Brazil
Fundação Antônio Prudente - AC Camargo Câncer Center
🇧🇷São Paulo, Brazil
CHRU Grenoble
🇫🇷Grenoble, France
Institut Gustave Roussy
🇫🇷Villejuif, France