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)

Squamous Cell Carcinoma Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284424
• Other study ID #: 3475-629
• Secondary ID: MK-3475-629KEYNO
• Status: Completed
• Phase: Phase 2
• Start date: October 26, 2017
• Est. completion date: September 13, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: September 13, 2023
• Est. primary completion date: July 29, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Squamous Cell Carcinoma

Intervention

Biological:
• Pembrolizumab
IV infusion

Locations

Country	Name	City	State
Australia	The Townsville Hospital ( Site 0404)	Douglas
Australia	Royal Brisbane and Women s Hospital ( Site 0407)	Herston	Queensland
Australia	Lismore Base Hospital ( Site 0402)	Lismore
Australia	Orange Health Services ( Site 0406)	Orange	New South Wales
Australia	Southern Medical Day Care Centre ( Site 0408)	Wollongong	New South Wales
Australia	Princess Alexandra Hospital ( Site 0405)	Woolloongabba	Queensland
Canada	Dr. Leon Richard Oncology Centre ( Site 0100)	Moncton	New Brunswick
Canada	Jewish General Hospital ( Site 0103)	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre ( Site 0101)	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre ( Site 0102)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0105)	Toronto	Ontario
France	Hopital Avicenne ( Site 0609)	Bobigny
France	CHRU Lille - Hopital Claude Huriez ( Site 0605)	Lille
France	CHU Limoges CHU Dupuytren ( Site 0608)	Limoges
France	Hopital La Timone ( Site 0603)	Marseille
France	Hopital Archet 3 ( Site 0607)	Nice cedex 3
France	Hopital Saint-Louis ( Site 0601)	Paris
France	CH Lyon Sud Hospices Civils de Lyon ( Site 0600)	Pierre Benite
France	CHU Reims - Hopital Robert Debre ( Site 0610)	Reims
France	IUCT - Oncopole ( Site 0604)	Toulouse	Cedex 9
France	Institut Gustave Roussy (IGR) ( Site 0602)	Villejuif
Germany	Universitaetsklinikum Essen ( Site 0650)	Essen
Germany	Medizinische Hochschule Hannover ( Site 0652)	Hannover
Germany	Universitaets-Hautklinik Kiel ( Site 0656)	Kiel
Germany	Universitaetsklinikum Mannheim GmbH ( Site 0654)	Mannheim
Germany	Universitatsklinikum Tübingen ( Site 0651)	Tuebingen
Israel	Rambam Health Care Campus ( Site 0950)	Haifa
Israel	Rabin Medical Center ( Site 0952)	Petah Tikva
Israel	Sheba Medical Center ( Site 0953)	Ramat Gan
Israel	Sourasky Medical Center. ( Site 0951)	Tel-Aviv
Mexico	Centro Estatal de Cancerologia de Chihuahua ( Site 0308)	Chihuahua
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0301)	Guadalajara	Jalisco
Mexico	Grupo Medico Camino SC ( Site 0300)	Mexico City
Mexico	Hospital y Clinica OCA SA de CV/Monterrey International ResearchCenter ( Site 0306)	Monterrey	Nuevo Leon
Norway	Haukeland Universitetssykehus ( Site 0902)	Bergen
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 0901)	Oslo
Spain	Hospital Clinic i Provincial Barcelona ( Site 0754)	Barcelona
Spain	Hospital Vall D Hebron ( Site 0750)	Barcelona
Spain	Hospital Duran i Reinals ICO de Hospitalet ( Site 0751)	Hospitalet del Llobregat	Barcelona
Spain	Hospital Universitario Ramon y Cajal ( Site 0753)	Madrid
Spain	Hospital General de Valencia ( Site 0752)	Valencia
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust ( Site 0803)	Bebington	Wirral
United Kingdom	Royal Marsden NHS Foundation Trust ( Site 0800)	London
United Kingdom	University College Hospital NHS Foundation Trust ( Site 0801)	London
United Kingdom	Royal Cornwall Hospitals NHS Trust ( Site 0804)	Truro
United States	Massachusetts General Hospital ( Site 0362)	Boston	Massachusetts
United States	Texas Oncology PA ( Site 8000)	Dallas	Texas
United States	John Theurer Cancer Center at Hackensack University Med Ctr ( Site 0367)	Hackensack	New Jersey
United States	Indiana University Melvin and Bren Simon Cancer Center ( Site 0353)	Indianapolis	Indiana
United States	Moores UC San Diego Cancer Center ( Site 0352)	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada ( Site 8001)	Las Vegas	Nevada
United States	Yale University ( Site 0365)	New Haven	Connecticut
United States	Stanford University Medical Center ( Site 0366)	Palo Alto	California
United States	Fox Chase Cancer Center ( Site 0351)	Philadelphia	Pennsylvania
United States	St. Joseph Heritage Healthcare ( Site 0350)	Santa Rosa	California
United States	Sanford Cancer Center Oncology Clinic ( Site 0356)	Sioux Falls	South Dakota
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0364)	Tulsa	Oklahoma
United States	Lombardi Comprehensive Cancer Center ( Site 0360)	Washington	District of Columbia
United States	University of Kansas Cancer Center ( Site 0361)	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Israel,  Mexico,  Norway,  Spain,  United Kingdom, 

References & Publications (1)

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- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 31.8 months (database cutoff date 29-Jul-2020)
Secondary	Duration of Response (DOR)		Up to approximately 56 months
Secondary	Disease Control Rate (DCR)		Up to approximately 56 months
Secondary	Progression-free Survival (PFS)		Up to approximately 56 months
Secondary	Overall Survival (OS)		Up to approximately 56 months
Secondary	Number of Participants Who Experienced One or More Adverse Events (AEs)		Up to approximately 56 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)		Up to approximately 56 months

External Links

•   Merck Clinical Trial Information