Clinical trial NCT04050436: Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer
Official title: A Randomized, Controlled, Open-Label, Phase 2 Study of Cemiplimab as a Single Agent and in Combination With RP1 in Patients With Advanced Cutaneous Squamous Cell Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cutaneous Squamous Cell Carcinoma
Advanced Cutaneous Squamous Cell Carcinoma
Metastatic Cutaneous Squamous Cell Carcinoma
Keywords: Oncolytic Virus
Carcinoma
Carcinoma, Squamous Cell
Cemiplimab
Metastatic Cutaneous Squamous Cell Carcinoma
Oncolytic Immuno-gene therapy
Lead sponsor: Replimune Inc.
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2019-08-08
Enrollment: 231
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: 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.

Eligibility criteria: Key Inclusion Criteria:

* 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 Exclusion Criteria:

* 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.

Primary outcomes:
measure: Objective Response Rate (ORR) according to blinded independent review
timeFrame: up to 5 years
measure: Complete Response Rate (CRR) according to blinded independent review
timeFrame: up to 5 years
Secondary outcomes:
measure: Progression Free Survival (PFS) by blinded independent review.
timeFrame: up to 5 years
measure: ORR/CRR by investigator assessment and blinded independent review
timeFrame: up to 5 years
measure: ORR/CRR for patients with metastatic or locally advanced disease according to investigator review and blinded independent review
timeFrame: up to 5 years
measure: ORR/CRR for patients who have and have not previously received systemic CSCC-directed therapy and blinded independent review
timeFrame: up to 5 years
measure: Duration of Response (DOR) per investigator review and blinded independent review
timeFrame: up to 5 years
measure: Progression-free Survival (PFS) per investigator review
timeFrame: up to 5 years
measure: Overall Survival (OS)
timeFrame: up to 5 years
measure: 3-year survival
timeFrame: 3 years
measure: 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)
timeFrame: approximately 30 months
measure: Evaluation of the safety and tolerability of cemiplimab alone and combined with RP1 as assessed via adverse events (AEs)
timeFrame: approximately 26 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Miami
country: United States
facility: University of Miami Health System
state: Florida
city: Orlando
country: United States
facility: Orlando Health UF Health Cancer Center
state: Florida
city: Tampa
country: United States
facility: Moffitt McKinley Outpatient Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack Univeristy Medical Center
state: New Jersey
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University Of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Wollongong
country: Australia
facility: Cancer Care Wollongong Pty Limited
state: New South Wales
city: Southport
country: Australia
facility: Tasman Oncology Research Ltd
state: Queensland
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Panagyurishte
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment - Uni Hospital" OOD Department of Medical Oncology
city: Plovdiv
country: Bulgaria
facility: "Complex Oncology Center - Plovdiv" EOOD Department of Medical Oncology and Cutaneous Cancer Diseases "
city: Toronto
country: Canada
facility: Sunnybrook Health Science Centre
state: Ontario
city: Besancon
country: France
facility: CHU Besancon - Hopital Jean Minjoz
city: Dijon
country: France
facility: CHU Dijon Hopital F. Mitterrand Service de Dermatologie - UMAC
city: La Tronche
country: France
facility: CHU de Grenoble - Hopital A Michallon
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Centre Léon Bérard
city: Marseille
country: France
facility: Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone
city: Nice
country: France
facility: CHU Nice - Hopital de l'Archet 2
city: Paris
country: France
facility: Hospital Saint Louis
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite Universitatsmedizin Berlin
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Hamburg
country: Germany
facility: Universitätsklinikum Eppendorf
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg: National Centre for Tumour Diseases (NCT)
city: München
country: Germany
facility: University Hospital Munchen (LMU)
city: Tübingen
country: Germany
facility: Universitatsklinikum Tubingen Zentrum fur Dermatoonkologie
city: Athens
country: Greece
facility: Hippocratio General Hospital of Athens
city: Athens
country: Greece
facility: Attiko University Hospital
city: Athens
country: Greece
facility: Andreas Syggros Hospital
city: Athens
country: Greece
facility: General Hospital of Athens "Laiko", 1st Department of Medicine, University of Athens Medical School
city: Bari
country: Italy
facility: Istituto Tumori "Giovanni Paolo II" IRCCS
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne; Centrum Leczenia Czerniaka w Gdańsku
city: Kraków
country: Poland
facility: Narodowy Instytut Onkologii; Panstwowy Instytut Badawczy Oddzial w Krakowie
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii; Panstwowy Instytut Badawczy
city: Wrocław
country: Poland
facility: Klinika Dermatologii, Wenerologii i Alergologii, USK im J. Mikulicza-Radeckiego we Wroclawiu
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
city: Valencia
country: Spain
facility: Hospital General Universitario De Valencia
Study officials:
affiliation: Lead Medical Monitor
name: Moran Mishal, MD
role: STUDY_DIRECTOR
affiliation: Secondary Medical Monitor
name: Jeannie Hou, MD
role: STUDY_DIRECTOR
References: