Clinical trial NCT03284424: 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)
Official title: A Phase 2, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Pembrolizumab in Participants With Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (R/M cSCC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2017-09-15
Enrollment: 159
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 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 32 months
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to approximately 56 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 56 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 56 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 56 months
measure: Number of Participants Who Experienced One or More Adverse Events (AEs)
timeFrame: Up to approximately 56 months
measure: Number of Participants Who Discontinued Study Treatment Due to AE
timeFrame: Up to approximately 56 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center ( Site 0352)
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center ( Site 0366)
state: California
city: Santa Rosa
country: United States
facility: St. Joseph Heritage Healthcare ( Site 0350)
state: California
city: New Haven
country: United States
facility: Yale University ( Site 0365)
state: Connecticut
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center ( Site 0360)
state: District of Columbia
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center ( Site 0353)
state: Indiana
city: Westwood
country: United States
facility: University of Kansas Cancer Center ( Site 0361)
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital ( Site 0362)
state: Massachusetts
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada ( Site 8001)
state: Nevada
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0367)
state: New Jersey
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0364)
state: Oklahoma
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center ( Site 0351)
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center Oncology Clinic ( Site 0356)
state: South Dakota
city: Dallas
country: United States
facility: Texas Oncology PA ( Site 8000)
state: Texas
city: Orange
country: Australia
facility: Orange Health Services ( Site 0406)
state: New South Wales
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre ( Site 0408)
state: New South Wales
city: Herston
country: Australia
facility: Royal Brisbane and Women s Hospital ( Site 0407)
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital ( Site 0405)
state: Queensland
city: Douglas
country: Australia
facility: The Townsville Hospital ( Site 0404)
city: Lismore
country: Australia
facility: Lismore Base Hospital ( Site 0402)
city: Moncton
country: Canada
facility: Dr. Leon Richard Oncology Centre ( Site 0100)
state: New Brunswick
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre ( Site 0101)
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute ( Site 0105)
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre ( Site 0102)
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital ( Site 0103)
state: Quebec
city: Toulouse
country: France
facility: IUCT - Oncopole ( Site 0604)
state: Cedex 9
city: Bobigny
country: France
facility: Hopital Avicenne ( Site 0609)
city: Lille
country: France
facility: CHRU Lille - Hopital Claude Huriez ( Site 0605)
city: Limoges
country: France
facility: CHU Limoges CHU Dupuytren ( Site 0608)
city: Marseille
country: France
facility: Hopital La Timone ( Site 0603)
city: Nice cedex 3
country: France
facility: Hopital Archet 3 ( Site 0607)
city: Paris
country: France
facility: Hopital Saint-Louis ( Site 0601)
city: Pierre Benite
country: France
facility: CH Lyon Sud Hospices Civils de Lyon ( Site 0600)
city: Reims
country: France
facility: CHU Reims - Hopital Robert Debre ( Site 0610)
city: Villejuif
country: France
facility: Institut Gustave Roussy (IGR) ( Site 0602)
city: Essen
country: Germany
facility: Universitaetsklinikum Essen ( Site 0650)
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover ( Site 0652)
city: Kiel
country: Germany
facility: Universitaets-Hautklinik Kiel ( Site 0656)
city: Mannheim
country: Germany
facility: Universitaetsklinikum Mannheim GmbH ( Site 0654)
city: Tuebingen
country: Germany
facility: Universitatsklinikum Tübingen ( Site 0651)
city: Haifa
country: Israel
facility: Rambam Health Care Campus ( Site 0950)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center ( Site 0952)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center ( Site 0953)
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center. ( Site 0951)
city: Guadalajara
country: Mexico
facility: Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0301)
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital y Clinica OCA SA de CV/Monterrey International ResearchCenter ( Site 0306)
state: Nuevo Leon
city: Chihuahua
country: Mexico
facility: Centro Estatal de Cancerologia de Chihuahua ( Site 0308)
city: Mexico City
country: Mexico
facility: Grupo Medico Camino SC ( Site 0300)
city: Bergen
country: Norway
facility: Haukeland Universitetssykehus ( Site 0902)
city: Oslo
country: Norway
facility: Oslo Universitetssykehus Radiumhospitalet ( Site 0901)
city: Hospitalet del Llobregat
country: Spain
facility: Hospital Duran i Reinals ICO de Hospitalet ( Site 0751)
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital Vall D Hebron ( Site 0750)
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial Barcelona ( Site 0754)
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal ( Site 0753)
city: Valencia
country: Spain
facility: Hospital General de Valencia ( Site 0752)
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0803)
state: Wirral
city: London
country: United Kingdom
facility: University College Hospital NHS Foundation Trust ( Site 0801)
city: London
country: United Kingdom
facility: Royal Marsden NHS Foundation Trust ( Site 0800)
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospitals NHS Trust ( Site 0804)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Grob JJ, Gonzalez R, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Zhang P, Gumuscu B, Swaby RF, Hughes BGM. Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629). J Clin Oncol. 2020 Sep 1;38(25):2916-2925. doi: 10.1200/JCO.19.03054. Epub 2020 Jul 16.
citation: Hughes BGM, Mendoza RG, Basset-Seguin N, Vornicova O, Schachter J, Joshi A, Meyer N, Grange F, Piulats JM, Bauman JR, Chirovsky D, Zhang P, Gumuscu B, Swaby RF, Grob JJ. Health-Related Quality of Life of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma Treated with Pembrolizumab in KEYNOTE-629. Dermatol Ther (Heidelb). 2021 Oct;11(5):1777-1790. doi: 10.1007/s13555-021-00598-6. Epub 2021 Sep 23.