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)

NCT03284424 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: 3475-629MK-3475-629KEYNOTE-6292017-000594-37
• Study Type: interventional
• Target: 159
• Locations: 10 countries
• Sites: 59

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.

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)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Duration of Response (DOR)

  Up to approximately 56 months

• Disease Control Rate (DCR)

  Up to approximately 56 months

• Progression-free Survival (PFS)

  Up to approximately 56 months

• Overall Survival (OS)

  Up to approximately 56 months

• Number of Participants Who Experienced One or More Adverse Events (AEs)

  Up to approximately 56 months

Study Arms (2)

R/M cSCC cohort

EXPERIMENTAL

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

LA cSCC cohort

EXPERIMENTAL

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

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: KEYTRUDA®, MK-3475

LA cSCC cohort; R/M cSCC cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (59)

Moores UC San Diego Cancer Center ( Site 0352)

La Jolla, California, 92093-0880, United States

Location

Stanford University Medical Center ( Site 0366)

Palo Alto, California, 94305, United States

Location

St. Joseph Heritage Healthcare ( Site 0350)

Santa Rosa, California, 95403, United States

Location

Yale University ( Site 0365)

New Haven, Connecticut, 06520, United States

Location

Lombardi Comprehensive Cancer Center ( Site 0360)

Washington D.C., District of Columbia, 20007, United States

Location

Indiana University Melvin and Bren Simon Cancer Center ( Site 0353)

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Cancer Center ( Site 0361)

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital ( Site 0362)

Boston, Massachusetts, 02114, United States

Location

Comprehensive Cancer Centers of Nevada ( Site 8001)

Las Vegas, Nevada, 89148, United States

Location

John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0367)

Hackensack, New Jersey, 07601, United States

Location

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0364)

Tulsa, Oklahoma, 74146, United States

Location

Fox Chase Cancer Center ( Site 0351)

Philadelphia, Pennsylvania, 19111, United States

Location

Sanford Cancer Center Oncology Clinic ( Site 0356)

Sioux Falls, South Dakota, 57104, United States

Location

Texas Oncology PA ( Site 8000)

Dallas, Texas, 75246, United States

Location

Orange Health Services ( Site 0406)

Orange, New South Wales, 2800, Australia

Location

Southern Medical Day Care Centre ( Site 0408)

Wollongong, New South Wales, 2500, Australia

Location

Royal Brisbane and Women s Hospital ( Site 0407)

Herston, Queensland, 4029, Australia

Location

Princess Alexandra Hospital ( Site 0405)

Woolloongabba, Queensland, 4102, Australia

Location

The Townsville Hospital ( Site 0404)

Douglas, 4814, Australia

Location

Lismore Base Hospital ( Site 0402)

Lismore, 2480, Australia

Location

Dr. Leon Richard Oncology Centre ( Site 0100)

Moncton, New Brunswick, E1C 8X3, Canada

Location

The Ottawa Hospital Cancer Centre ( Site 0101)

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Research Institute ( Site 0105)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0102)

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital ( Site 0103)

Montreal, Quebec, H3T 1E2, Canada

Location

IUCT - Oncopole ( Site 0604)

Toulouse, Cedex 9, 31059, France

Location

Hopital Avicenne ( Site 0609)

Bobigny, 93009, France

Location

CHRU Lille - Hopital Claude Huriez ( Site 0605)

Lille, 59037, France

Location

CHU Limoges CHU Dupuytren ( Site 0608)

Limoges, 87042, France

Location

Hopital La Timone ( Site 0603)

Marseille, 13005, France

Location

Hopital Archet 3 ( Site 0607)

Nice, 06202, France

Location

Hopital Saint-Louis ( Site 0601)

Paris, 75010, France

Location

CH Lyon Sud Hospices Civils de Lyon ( Site 0600)

Pierre-Bénite, 69310, France

Location

CHU Reims - Hopital Robert Debre ( Site 0610)

Reims, 51092, France

Location

Institut Gustave Roussy (IGR) ( Site 0602)

Villejuif, 94805, France

Location

Universitaetsklinikum Essen ( Site 0650)

Essen, 45147, Germany

Location

Medizinische Hochschule Hannover ( Site 0652)

Hanover, 30625, Germany

Location

Universitaets-Hautklinik Kiel ( Site 0656)

Kiel, 24105, Germany

Location

Universitaetsklinikum Mannheim GmbH ( Site 0654)

Mannheim, 68167, Germany

Location

Universitatsklinikum Tübingen ( Site 0651)

Tübingen, 72076, Germany

Location

Rambam Health Care Campus ( Site 0950)

Haifa, 3109601, Israel

Location

Rabin Medical Center ( Site 0952)

Petah Tikva, 4963211, Israel

Location

Sheba Medical Center ( Site 0953)

Ramat Gan, 5266202, Israel

Location

Sourasky Medical Center. ( Site 0951)

Tel Aviv, 6423906, Israel

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0301)

Guadalajara, Jalisco, 44200, Mexico

Location

Hospital y Clinica OCA SA de CV/Monterrey International ResearchCenter ( Site 0306)

Monterrey, Nuevo León, 64000, Mexico

Location

Centro Estatal de Cancerologia de Chihuahua ( Site 0308)

Chihuahua City, 31000, Mexico

Location

Grupo Medico Camino SC ( Site 0300)

Mexico City, 03310, Mexico

Location

Haukeland Universitetssykehus ( Site 0902)

Bergen, 5021, Norway

Location

Oslo Universitetssykehus Radiumhospitalet ( Site 0901)

Oslo, 0379, Norway

Location

Hospital Duran i Reinals ICO de Hospitalet ( Site 0751)

Hospitalet Del Llobregat, Barcelona, 08908, Spain

Location

Hospital Vall D Hebron ( Site 0750)

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial Barcelona ( Site 0754)

Barcelona, 08036, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 0753)

Madrid, 28034, Spain

Location

Hospital General de Valencia ( Site 0752)

Valencia, 46014, Spain

Location

The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0803)

Bebington, Wirral, CH63 4JY, United Kingdom

Location

University College Hospital NHS Foundation Trust ( Site 0801)

London, NW1 2PG, United Kingdom

Location

Royal Marsden NHS Foundation Trust ( Site 0800)

London, SW3 6JJ, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust ( Site 0804)

Truro, TR1 3LQ, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 32673170 RESULT

• Bratland A, Munoz-Couselo E, Mortier L, Roshdy O, Gonzalez R, Schachter J, Arance AM, Grange F, Meyer N, Joshi AJ, Billan S, Hughes BGM, Grob JJ, Ramakrishnan K, Ge J, Gumuscu B, Swaby RF, Gutzmer R. Health-Related Quality of Life with Pembrolizumab in Patients with Locally Advanced or Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: KEYNOTE-629. Dermatol Ther (Heidelb). 2023 Dec;13(12):3165-3180. doi: 10.1007/s13555-023-01059-y. Epub 2023 Nov 9.

  PMID: 37943491 DERIVED

• 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.

  PMID: 34558040 DERIVED

Related Links

• Merck Clinical Trial Information

MeSH Terms

Conditions

Carcinoma, Squamous Cell; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 15, 2017
• Study Start: October 26, 2017
• Primary Completion: July 29, 2020
• Study Completion: September 13, 2023
• Last Updated: August 23, 2024
• Results First Posted: November 19, 2021

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

AU (6); FR (10); GB (4); ME (4); NO (2); IL (4); ES (5); DE (5); US (14); CA (5)