Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer
- Conditions
- Advanced Cutaneous Squamous Cell CarcinomaMetastatic Cutaneous Squamous Cell CarcinomaCutaneous Squamous Cell Carcinoma
- Interventions
- Drug: CemiplimabBiological: RP1
- Registration Number
- NCT04050436
- Lead Sponsor
- Replimune Inc.
- Brief Summary
To estimate the clinical benefit of cemiplimab monotherapy versus cemiplimab in combination with RP1 for patients with locally advanced or metastatic CSCC, as assessed by overall response rate (ORR) and complete response rate (CRR) according to blinded independent review.
- Detailed Description
RP1 is a selectively replication competent herpes simplex virus type 1(HSV-1). This is a Phase 1/2, open-label, multicenter repeat-dosing study of RP1 alone and in combination with nivolumab in patients with advanced malignancies, and contains both single agent dose escalation, dose expansion to include nivolumab, and the combination in multiple Phase 2 cohorts in individual tumor types.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 231
- Histologically confirmed locally advanced or metastatic cutaneous squamous cell carcinoma
- Patients with locally advanced disease who are not suitable candidates for surgical or radiological treatment of lesions or have refused those treatments
- At least 1 lesion that is measurable and injectable by study criteria
- Eastern Cooperative Oncology Group (ECOG) performance status ≤1. Patients with ECOG PS 2 at baseline may be allowed to enroll if PS 2 status is only related to the CSCC disease under study
- Anticipated life expectancy >12 weeks
- All patients must consent to provide archived or newly obtained tumor material for central pathology review for confirmation of diagnosis of CSCC.
Key
- Prior treatment with an oncolytic therapy
- Patients with active significant herpetic infections or prior complications of HSV-1 infection (e.g. herpetic keratitis or encephalitis)
- Patients who require intermittent or chronic use of systemic (oral or intravenous) anti-virals with known anti-herpetic activity (e.g. acyclovir)
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
- Prior treatment with an agent that blocks the PD-1/PD-L1 pathway.
- Prior treatment with other immune modulating agents other than as adjuvant or neoadjuvant therapy within 3 years.
- Untreated brain metastasis(es) that may be considered active.
- Acute or chronic active hepatitis B or known history of hepatitis B or hepatitis C or human immunodeficiency virus (HIV) infection
- History of ILD/pneumonitis within the last 5 years or a history of ILD/pneumonitis requiring treatment with systemic steroids.
- Any major or surgical procedure ≤ 28 days before randomization
- Administration of live vaccines ≤ 28 days before randomization
Note: Other protocol defined Inclusion/Exclusion criteria apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cemiplimab in combination with RP1 Cemiplimab Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks Cemiplimab in combination with RP1 RP1 Cemiplimab administered intravenously every 3 weeks in combination with RP1 administered as an intratumoral injection every 3 weeks Cemiplimab Cemiplimab Cemiplimab administered intravenously as a single therapy every 3 weeks
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) according to blinded independent review up to 5 years Complete Response Rate (CRR) according to blinded independent review up to 5 years
- Secondary Outcome Measures
Name Time Method Change in overall scores of patient-reported outcomes in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) approximately 30 months Evaluation of the safety and tolerability of cemiplimab alone and combined with RP1 as assessed via adverse events (AEs) approximately 26 months ORR/CRR for patients who have and have not previously received systemic CSCC-directed therapy and blinded independent review up to 5 years Overall Survival (OS) up to 5 years Progression Free Survival (PFS) by blinded independent review. up to 5 years ORR/CRR by investigator assessment and blinded independent review up to 5 years 3-year survival 3 years ORR/CRR for patients with metastatic or locally advanced disease according to investigator review and blinded independent review up to 5 years Progression-free Survival (PFS) per investigator review up to 5 years Duration of Response (DOR) per investigator review and blinded independent review up to 5 years
Trial Locations
- Locations (56)
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
CHU Besancon - Hopital Jean Minjoz
🇫🇷Besancon, France
Universitatsklinikum Heidelberg: National Centre for Tumour Diseases (NCT)
🇩🇪Heidelberg, Germany
University Of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Hospital Saint Louis
🇫🇷Paris, France
Universitatsklinikum Tubingen Zentrum fur Dermatoonkologie
🇩🇪Tübingen, Germany
General Hospital of Athens "Laiko", 1st Department of Medicine, University of Athens Medical School
🇬🇷Athens, Greece
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
CHU Dijon Hopital F. Mitterrand Service de Dermatologie - UMAC
🇫🇷Dijon, France
CHU Nice - Hopital de l'Archet 2
🇫🇷Nice, France
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Tasman Oncology Research Ltd
🇦🇺Southport, Queensland, Australia
Hospital General Universitario De Valencia
🇪🇸Valencia, Spain
Istituto Tumori "Giovanni Paolo II" IRCCS
🇮🇹Bari, Italy
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Centre Léon Bérard
🇫🇷Lyon, France
Attiko University Hospital
🇬🇷Athens, Greece
CHRU de Lille
🇫🇷Lille, France
Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone
🇫🇷Marseille, France
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Spain
Charite Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
University Hospital Munchen (LMU)
🇩🇪München, Germany
Clinica Universitaria de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Virgen de la Arrixaca
🇪🇸Murcia, Spain
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Ohio State University Comprehensive Cancer Center
🇺🇸Columbus, Ohio, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Sunnybrook Health Science Centre
🇨🇦Toronto, Ontario, Canada
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
University of California San Diego
🇺🇸La Jolla, California, United States
Stanford University
🇺🇸Stanford, California, United States
University of Miami Health System
🇺🇸Miami, Florida, United States
John Theurer Cancer Center at Hackensack Univeristy Medical Center
🇺🇸Hackensack, New Jersey, United States
Moffitt McKinley Outpatient Center
🇺🇸Tampa, Florida, United States
Winship Cancer Institute of Emory University
🇺🇸Atlanta, Georgia, United States
Cancer Care Wollongong Pty Limited
🇦🇺Wollongong, New South Wales, Australia
CHU de Grenoble - Hopital A Michallon
🇫🇷La Tronche, France
Universitatsklinikum Essen
🇩🇪Essen, Germany
Universitätsklinikum Eppendorf
🇩🇪Hamburg, Germany
Narodowy Instytut Onkologii; Panstwowy Instytut Badawczy Oddzial w Krakowie
🇵🇱Kraków, Poland
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Multiprofile Hospital for Active Treatment - Uni Hospital" OOD Department of Medical Oncology
🇧🇬Panagyurishte, Bulgaria
"Complex Oncology Center - Plovdiv" EOOD Department of Medical Oncology and Cutaneous Cancer Diseases "
🇧🇬Plovdiv, Bulgaria
Monash Medical Centre
🇦🇺Clayton, Victoria, Australia
The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia
Klinika Dermatologii, Wenerologii i Alergologii, USK im J. Mikulicza-Radeckiego we Wroclawiu
🇵🇱Wrocław, Poland
Andreas Syggros Hospital
🇬🇷Athens, Greece
Uniwersyteckie Centrum Kliniczne; Centrum Leczenia Czerniaka w Gdańsku
🇵🇱Gdańsk, Poland
Hippocratio General Hospital of Athens
🇬🇷Athens, Greece
Narodowy Instytut Onkologii; Panstwowy Instytut Badawczy
🇵🇱Warsaw, Poland
Hospices Civils de Lyon
🇫🇷Pierre-Bénite, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Orlando Health UF Health Cancer Center
🇺🇸Orlando, Florida, United States
Prisma Health Cancer Institute
🇺🇸Greenville, South Carolina, United States