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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Squamous Cell Carcinoma
• Intervention / Treatment: Biological: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Douglas, Australia, 4814
    • The Townsville Hospital ( Site 0404)
  • Lismore, Australia, 2480
    • Lismore Base Hospital ( Site 0402)
  • New South Wales
    • Orange, New South Wales, Australia, 2800
      • Orange Health Services ( Site 0406)
    • Wollongong, New South Wales, Australia, 2500
      • Southern Medical Day Care Centre ( Site 0408)
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women s Hospital ( Site 0407)
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 0405)
• Canada
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 8X3
      • Dr. Leon Richard Oncology Centre ( Site 0100)
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre ( Site 0101)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0102)
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Research Institute ( Site 0105)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0103)
• France
  • Bobigny, France, 93009
    • Hopital Avicenne ( Site 0609)
  • Lille, France, 59037
    • CHRU Lille - Hopital Claude Huriez ( Site 0605)
  • Limoges, France, 87042
    • CHU Limoges CHU Dupuytren ( Site 0608)
  • Marseille, France, 13005
    • Hopital La Timone ( Site 0603)
  • Nice cedex 3, France, 06202
    • Hopital Archet 3 ( Site 0607)
  • Paris, France, 75010
    • Hopital Saint-Louis ( Site 0601)
  • Pierre Benite, France, 69310
    • CH Lyon Sud Hospices Civils de Lyon ( Site 0600)
  • Reims, France, 51092
    • CHU Reims - Hopital Robert Debre ( Site 0610)
  • Villejuif, France, 94805
    • Institut Gustave Roussy (IGR) ( Site 0602)
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
      • IUCT - Oncopole ( Site 0604)
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen ( Site 0650)
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover ( Site 0652)
  • Kiel, Germany, 24105
    • Universitaets-Hautklinik Kiel ( Site 0656)
  • Mannheim, Germany, 68167
    • Universitaetsklinikum Mannheim GmbH ( Site 0654)
  • Tuebingen, Germany, 72076
    • Universitatsklinikum Tübingen ( Site 0651)
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus ( Site 0950)
  • Petah Tikva, Israel, 4963211
    • Rabin Medical Center ( Site 0952)
  • Ramat Gan, Israel, 5266202
    • Sheba Medical Center ( Site 0953)
  • Tel-Aviv, Israel, 6423906
    • Sourasky Medical Center. ( Site 0951)
• Mexico
  • Chihuahua, Mexico, 31000
    • Centro Estatal de Cancerologia de Chihuahua ( Site 0308)
  • Mexico City, Mexico, 03310
    • Grupo Medico Camino SC ( Site 0300)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44200
      • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0301)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64000
      • Hospital y Clinica OCA SA de CV/Monterrey International ResearchCenter ( Site 0306)
• Norway
  • Bergen, Norway, 5021
    • Haukeland Universitetssykehus ( Site 0902)
  • Oslo, Norway, 0379
    • Oslo Universitetssykehus Radiumhospitalet ( Site 0901)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall D Hebron ( Site 0750)
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial Barcelona ( Site 0754)
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal ( Site 0753)
  • Valencia, Spain, 46014
    • Hospital General de Valencia ( Site 0752)
  • Barcelona
    • Hospitalet del Llobregat, Barcelona, Spain, 08908
      • Hospital Duran i Reinals ICO de Hospitalet ( Site 0751)
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College Hospital NHS Foundation Trust ( Site 0801)
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Foundation Trust ( Site 0800)
  • Truro, United Kingdom, TR1 3LQ
    • Royal Cornwall Hospitals NHS Trust ( Site 0804)
  • Wirral
    • Bebington, Wirral, United Kingdom, CH63 4JY
      • The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0803)
• United States
  • California
    • La Jolla, California, United States, 92093-0880
      • Moores UC San Diego Cancer Center ( Site 0352)
    • Palo Alto, California, United States, 94305
      • Stanford University Medical Center ( Site 0366)
    • Santa Rosa, California, United States, 95403
      • St. Joseph Heritage Healthcare ( Site 0350)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University ( Site 0365)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center ( Site 0360)
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Cancer Center ( Site 0353)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center ( Site 0361)
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ( Site 0362)
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada ( Site 8001)
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0367)
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0364)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center ( Site 0351)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center Oncology Clinic ( Site 0356)
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology PA ( Site 8000)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: R/M cSCC cohort; 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Experimental: LA cSCC cohort; 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.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	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.	Up to approximately 32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	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.	Up to approximately 56 months
Disease Control Rate (DCR)	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.	Up to approximately 56 months
Progression-free Survival (PFS)	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.	Up to approximately 56 months
Overall Survival (OS)	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.	Up to approximately 56 months
Number of Participants Who Experienced One or More Adverse Events (AEs)	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.	Up to approximately 56 months
Number of Participants Who Discontinued Study Treatment Due to AE	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.	Up to approximately 56 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Merck Clinical Trial Information

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2017
• Primary Completion (Actual): July 29, 2020
• Study Completion (Actual): September 13, 2023

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 15, 2017

Study Record Updates

• Last Update Posted (Actual): August 23, 2024
• Last Update Submitted That Met QC Criteria: July 29, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2); Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-629; MK-3475-629 (Other Identifier: Merck); KEYNOTE-629 (Other Identifier: Merck); 2017-000594-37 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No