Study of Pembrolizumab (MK-3475) in Adults With Recurrent/Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) or Locally Advanced Unresectable cSCC (MK-3475-629/KEYNOTE-629)
- Conditions
- Squamous Cell Carcinoma
- Interventions
- Biological: Pembrolizumab
- Registration Number
- NCT03284424
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in adult participants with recurrent or metastatic(R/M) cutaneous Squamous Cell Carcinoma (cSCC) or locally advanced (LA) unresectable cSCC that is not amenable to surgery and/or radiation and/or systemic therapies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 159
- R/M cSCC cohort only:
- Has cSCC that is either metastatic defined as disseminated disease, and/or unresectable disease that is not curable by surgery or radiation.
- Has histologically-confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from an unknown primary cancer is not permitted).
- LA cSCC cohort only:
- Must be ineligible for surgical resection.
- Participants who received prior radiation therapy (RT) to index site or must be deemed to be not eligible for RT.
- Participants who received prior systemic therapy for curative intent are eligible regardless of regimen.
- R/M cSCC cohort only:
- Has metastatic disease defined as disseminated disease distant to the initial/primary site of diagnosis, and/or must have locally recurrent disease that has been previously treated (with either surgery or radiotherapy), and is not amenable to either curative surgery or radiotherapy.
- Has measurable disease based on RECIST 1.1 as assessed by the central imaging vendor.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 10 days prior to the start of study treatment.
- Has adequate organ function.
- Has a tissue sample adequate for programmed death-ligand 1 (PD-L1) testing as determined by central laboratory testing prior to study allocation.
- Has a life expectancy >3 months.
- Female participants of childbearing potential must agree to use an adequate method of contraception during the study treatment period and for at least 120 days after the last dose of study treatment.
- Has cSCC that can be cured with surgical resection, radiotherapy, or with a combination of surgery and radiotherapy.
- Has any other histologic type of skin cancer other than invasive squamous cell carcinoma as the primary disease under study, e.g. basal cell carcinoma that has not been definitively treated with surgery or radiation, Bowen's disease, Merkel cell carcinoma (MCC), melanoma.
- Has had any prior allogeneic solid organ or bone marrow transplantation.
- Has received prior therapy with an anti-programmed death protein-1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g. cytotoxic T-lymphocyte associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137]).
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study allocation.
(Notes: Participants must have recovered from all AEs due to previously administered therapies to ≤ Grade 1 or baseline. If a participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.)
- Has received prior radiotherapy within 2 weeks of start of study treatment.
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g. with use of disease-modifying agents, anticoagulants, corticosteroids or immunosuppressive drugs).
- Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection.
- Has a known history of Hepatitis B or known active Hepatitis C virus infection.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description R/M cSCC cohort Pembrolizumab Participants with R/M cSCC receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to approximately 2 years. LA cSCC cohort Pembrolizumab Participants with LA cSCC receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to approximately 2 years.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Up to approximately 32 months ORR was defined as the percentage of participants who have best response of Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) is presented.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) Up to approximately 56 months For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. The DOR per RECIST 1.1 as assessed by BICR is presented for all participants who experienced a confirmed CR or PR.
Disease Control Rate (DCR) Up to approximately 56 months DCR is defined as the percentage of participants who have a CR or PR or Stable Disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease). The DCR per RECIST 1.1 as assessed by BICR is presented.
Progression-free Survival (PFS) Up to approximately 56 months PFS was defined as the time from first dose of study treatment to the first documented PD or death due to any cause, whichever occurred first. PFS per RECIST 1.1 as assessed by BICR is presented.
Number of Participants Who Discontinued Study Treatment Due to AE Up to approximately 56 months An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who discontinued study treatment due to an AE is presented.
Overall Survival (OS) Up to approximately 56 months OS was defined as the time from first dose of study treatment to death due to any cause. The OS for all participants is presented.
Number of Participants Who Experienced One or More Adverse Events (AEs) Up to approximately 56 months An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy. The number of participants who experienced an AE is presented.
Trial Locations
- Locations (59)
Yale University ( Site 0365)
🇺🇸New Haven, Connecticut, United States
Lombardi Comprehensive Cancer Center ( Site 0360)
🇺🇸Washington, District of Columbia, United States
Sanford Cancer Center Oncology Clinic ( Site 0356)
🇺🇸Sioux Falls, South Dakota, United States
John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0367)
🇺🇸Hackensack, New Jersey, United States
Dr. Leon Richard Oncology Centre ( Site 0100)
🇨🇦Moncton, New Brunswick, Canada
Sourasky Medical Center. ( Site 0951)
🇮🇱Tel-Aviv, Israel
Grupo Medico Camino SC ( Site 0300)
🇲🇽Mexico City, Mexico
Stanford University Medical Center ( Site 0366)
🇺🇸Palo Alto, California, United States
CHU Reims - Hopital Robert Debre ( Site 0610)
🇫🇷Reims, France
Orange Health Services ( Site 0406)
🇦🇺Orange, New South Wales, Australia
Moores UC San Diego Cancer Center ( Site 0352)
🇺🇸La Jolla, California, United States
Hopital Saint-Louis ( Site 0601)
🇫🇷Paris, France
Texas Oncology PA ( Site 8000)
🇺🇸Dallas, Texas, United States
Princess Alexandra Hospital ( Site 0405)
🇦🇺Woolloongabba, Queensland, Australia
The Townsville Hospital ( Site 0404)
🇦🇺Douglas, Australia
Princess Margaret Cancer Centre ( Site 0102)
🇨🇦Toronto, Ontario, Canada
Southern Medical Day Care Centre ( Site 0408)
🇦🇺Wollongong, New South Wales, Australia
Universitaetsklinikum Mannheim GmbH ( Site 0654)
🇩🇪Mannheim, Germany
Rambam Health Care Campus ( Site 0950)
🇮🇱Haifa, Israel
Hospital Duran i Reinals ICO de Hospitalet ( Site 0751)
🇪🇸Hospitalet del Llobregat, Barcelona, Spain
Sheba Medical Center ( Site 0953)
🇮🇱Ramat Gan, Israel
University College Hospital NHS Foundation Trust ( Site 0801)
🇬🇧London, United Kingdom
Hospital Clinic i Provincial Barcelona ( Site 0754)
🇪🇸Barcelona, Spain
Universitaetsklinikum Essen ( Site 0650)
🇩🇪Essen, Germany
Universitaets-Hautklinik Kiel ( Site 0656)
🇩🇪Kiel, Germany
IUCT - Oncopole ( Site 0604)
🇫🇷Toulouse, Cedex 9, France
Hopital Archet 3 ( Site 0607)
🇫🇷Nice cedex 3, France
Royal Cornwall Hospitals NHS Trust ( Site 0804)
🇬🇧Truro, United Kingdom
Sunnybrook Research Institute ( Site 0105)
🇨🇦Toronto, Ontario, Canada
Rabin Medical Center ( Site 0952)
🇮🇱Petah Tikva, Israel
Centro Estatal de Cancerologia de Chihuahua ( Site 0308)
🇲🇽Chihuahua, Mexico
The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0803)
🇬🇧Bebington, Wirral, United Kingdom
CHU Limoges CHU Dupuytren ( Site 0608)
🇫🇷Limoges, France
Hopital La Timone ( Site 0603)
🇫🇷Marseille, France
CH Lyon Sud Hospices Civils de Lyon ( Site 0600)
🇫🇷Pierre Benite, France
Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0301)
🇲🇽Guadalajara, Jalisco, Mexico
Hospital Universitario Ramon y Cajal ( Site 0753)
🇪🇸Madrid, Spain
Hospital y Clinica OCA SA de CV/Monterrey International ResearchCenter ( Site 0306)
🇲🇽Monterrey, Nuevo Leon, Mexico
Hospital General de Valencia ( Site 0752)
🇪🇸Valencia, Spain
Hospital Vall D Hebron ( Site 0750)
🇪🇸Barcelona, Spain
Institut Gustave Roussy (IGR) ( Site 0602)
🇫🇷Villejuif, France
Universitatsklinikum Tübingen ( Site 0651)
🇩🇪Tuebingen, Germany
Oslo Universitetssykehus Radiumhospitalet ( Site 0901)
🇳🇴Oslo, Norway
Royal Marsden NHS Foundation Trust ( Site 0800)
🇬🇧London, United Kingdom
Massachusetts General Hospital ( Site 0362)
🇺🇸Boston, Massachusetts, United States
Comprehensive Cancer Centers of Nevada ( Site 8001)
🇺🇸Las Vegas, Nevada, United States
Indiana University Melvin and Bren Simon Cancer Center ( Site 0353)
🇺🇸Indianapolis, Indiana, United States
Lismore Base Hospital ( Site 0402)
🇦🇺Lismore, Australia
University of Kansas Cancer Center ( Site 0361)
🇺🇸Westwood, Kansas, United States
Medizinische Hochschule Hannover ( Site 0652)
🇩🇪Hannover, Germany
Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0364)
🇺🇸Tulsa, Oklahoma, United States
Fox Chase Cancer Center ( Site 0351)
🇺🇸Philadelphia, Pennsylvania, United States
Royal Brisbane and Women s Hospital ( Site 0407)
🇦🇺Herston, Queensland, Australia
The Ottawa Hospital Cancer Centre ( Site 0101)
🇨🇦Ottawa, Ontario, Canada
Jewish General Hospital ( Site 0103)
🇨🇦Montreal, Quebec, Canada
Hopital Avicenne ( Site 0609)
🇫🇷Bobigny, France
CHRU Lille - Hopital Claude Huriez ( Site 0605)
🇫🇷Lille, France
Haukeland Universitetssykehus ( Site 0902)
🇳🇴Bergen, Norway
St. Joseph Heritage Healthcare ( Site 0350)
🇺🇸Santa Rosa, California, United States