Study of Pembrolizumab Given Prior to Surgery and in Combination With Radiotherapy Given Post-surgery for Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-689)

Head and Neck Neoplasms Clinical Trial

Official title:

A Phase III, Randomized, Open-label Study to Evaluate Pembrolizumab as Neoadjuvant Therapy and in Combination With Standard of Care as Adjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma (LA HNSCC)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03765918
• Other study ID #: 3475-689
• Secondary ID: MK-3475-6892022-
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 17, 2018
• Est. completion date: September 10, 2026

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized, active-controlled, open-label study of pembrolizumab (Pembro) given prior to surgery and pembrolizumab in combination with standard of care radiotherapy (with or without cisplatin), as post-surgical therapy in treatment naïve participants with newly diagnosed Stage III/IVA, resectable, locoregionally advanced, head and neck squamous cell carcinoma (LA-HNSCC). Efficacy outcomes will be stratified by programmed cell death ligand 1 (PD-L1) combined positive score (CPS) status. The primary hypothesis is that pembrolizumab given before surgery and after surgery in combination with radiotherapy (with or without cisplatin) improves event-free survival compared to radiotherapy (with or without cisplatin) given after surgery alone.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 714
• Est. completion date: September 10, 2026
• Est. primary completion date: September 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed new diagnosis of resectable, non-metastatic, squamous cell carcinoma that is either: Stage III Human Papillomavirus (HPV) positive oropharyngeal primary that is tumor size (T) 4, lymph node involvement (N) 0-2, no distant metastases (M0); Stage III or IVA oropharyngeal HPV negative; or Stage III or IVA larynx/hypopharynx/oral cavity primaries.

• Is eligible for primary surgery based on investigator decision and per local practice

• Female and male participants of reproductive potential must agree to use adequate contraception throughout the study period and for up to 180 days after the last dose of study therapy.

• Male participants must refrain from donating sperm throughout the study period and for up to 180 days after the last dose of study therapy

• Female participant that is not pregnant or breastfeeding

• Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI), based on RECIST version 1.1

• Has provided newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

• Has results from testing of HPV status for oropharyngeal cancer defined as p16

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of randomization

Exclusion Criteria:

• Has Stage T4B and/or N3 LA HNSCC and/or distant metastases

• Has cancer outside of the oropharynx, larynx, and hypopharynx or oral cavity. such as nasopharyngeal, sinus, other para-nasal, or other unknown primary head and neck cancer (HNC)

• Female participant who has a positive urine pregnancy test within 72 hours prior to study start or within 24 hours prior to the start of radiotherapy with or without cisplatin.

• Has received prior therapy with an anti-programmed cell death receptor 1(PD-1), anti-programmed cell death receptor ligand 1(PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor

• Has received prior radiotherapy treatment or systemic anti-cancer therapy including investigational agents for the HNC under study prior to study start

• Has received a live vaccine within 30 days prior to randomization

• 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 randomization

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy

• Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system metastases and/or carcinomatous meningitis

• Has Grade =2 audiometric hearing loss

• Has Grade =2 neuropathy

• Has Grade 3-4 bleeding due to the underlying malignancy

• Has received major surgery or has not recovered adequately from the toxicity and/or complications from the intervention prior to study start

• Has had previous allogeneic tissue/solid organ transplant

• Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients, radiotherapy, cisplatin or their analogs

• Has an active autoimmune disease that has required systemic treatment in past 2 years

• Has a history of (non-infectious) 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 or is positive for Hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C (defined as Hepatitis C virus [HCV] ribonucleic acid is detected).

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the investigator

• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Squamous Cell Carcinoma of Head and Neck

Intervention

Biological:
• Pembrolizumab 200 mg
200 mg administered by intravenous (IV) infusion on Day 1 of each 21-day cycle

Radiation:
• Radiotherapy 60 Gray/day
Low risk participants administered 2 Gray/day in 30 fractions. Administered using intensity modulated radiation therapy.
• Radiotherapy 66 Gray/day
High risk participants administered 2 Gray/day in 33 fractions. Administered using intensity modulated radiation therapy.
• Radiotherapy 70 Gray/day
Participants with gross residual disease administered 2 Gray/day in 35 fractions. Administered using intensity modulated radiation therapy.

Drug:
• Cisplatin 100 mg/m^2
100 mg/m^2 administered by IV infusion on Day 1 of each 21-day cycle

Locations

Country	Name	City	State
Argentina	Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0019)	Buenos Aires	Caba
Argentina	Hospital Aleman Buenos Aires Argentina ( Site 0004)	Buenos Aires
Argentina	IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0016)	Buenos Aires
Argentina	Instituto de Oncología Angel Roffo ( Site 0003)	Buenos Aires
Argentina	Hospital Britanico de Buenos Aires ( Site 0012)	Ciudad de Buenos Aires	Caba
Argentina	Hospital Universitario Austral ( Site 0009)	Pilar	Buenos Aires
Argentina	Fundacion Estudios Clinicos-Oncology ( Site 0017)	Rosario	Santa Fe
Argentina	Hospital Provincial del Centenario ( Site 0008)	Rosario	Santa Fe
Argentina	Instituto de Oncologia de Rosario ( Site 0002)	Rosario	Santa Fe
Argentina	Sanatorio Britanico ( Site 0013)	Rosario	Santa Fe
Argentina	CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0010)	San Juan
Australia	Royal Brisbane and Women s Hospital ( Site 0050)	Herston	Queensland
Australia	The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 0051)	Westmead	New South Wales
Austria	Landeskrankenhaus - Universitatsklinikum Graz ( Site 1902)	Graz	Steiermark
Austria	Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 1901)	Linz	Oberosterreich
Austria	Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 1900)	Salzburg
Austria	Medizinische Universität Wien ( Site 1903)	Wien
Belgium	UZ Gent ( Site 0101)	Gent	Oost-Vlaanderen
Belgium	Hopital de Jolimont ( Site 0103)	Haine Saint Paul	Hainaut
Belgium	AZ Nikolaas ( Site 0104)	Sint-Niklaas	Oost-Vlaanderen
Brazil	Centro Regional Integrado de Oncologia ( Site 0160)	Fortaleza	Ceara
Brazil	Hospital Marcio Cunha-Unidade de Pesquisa Clínica ( Site 0177)	Ipatinga	Minas Gerais
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 0171)	Natal	Rio Grande Do Norte
Brazil	Hospital Nossa Senhora da Conceicao ( Site 0165)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0169)	Rio de Janeiro
Brazil	Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0155)	Salvador	Bahia
Brazil	Hospital de Base de Sao Jose de Rio Preto ( Site 0153)	Sao Jose do Rio Preto	Sao Paulo
Brazil	BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0175)	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0167)	Sao Paulo
Canada	Cross Cancer Institute ( Site 0201)	Edmonton	Alberta
Canada	McGill University Health Centre ( Site 0210)	Montreal	Quebec
Canada	CIUSSS de l'Estrie-CHUS ( Site 0209)	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0202)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0211)	Toronto	Ontario
Chile	Fundacion Arturo Lopez Perez FALP ( Site 0251)	Santiago	Region M. De Santiago
Colombia	Clinica de la Costa S.A.S. ( Site 0307)	Barranquilla	Atlantico
Colombia	Centro de Investigacion Clinica del Country ( Site 0304)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 0300)	Cali	Valle Del Cauca
Colombia	Oncologos del Occidente S.A. ( Site 0310)	Pereira	Risaralda
France	Institut Sainte Catherine ( Site 0352)	Avignon	Vaucluse
France	Hopital de la Timone ( Site 0356)	Marseille	Bouches-du-Rhone
France	Centre Antoine Lacassagne ( Site 0351)	Nice	Alpes-Maritimes
France	Hopital Europeen Georges Pompidou ( Site 0358)	Paris
France	Institut Curie ( Site 0350)	Paris
France	Institut Claudius Regaud IUCT Oncopole ( Site 0355)	Toulouse	Haute-Garonne
France	Institut Gustave Roussy ( Site 0353)	Villejuif	Val-de-Marne
Germany	Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 0414)	Berlin
Germany	Universitaetsklinikum Erlangen-Strahlenklinik ( Site 0412)	Erlangen	Bayern
Germany	Universitaetsklinikum Frankfurt ( Site 0403)	Frankfurt	Hessen
Germany	SRH Wald-Klinikum Gera GmbH ( Site 0406)	Gera	Thuringen
Germany	Universitaetsklinikum Hamburg Eppendorf ( Site 0407)	Hamburg
Germany	Klinikum Kassel GmbH ( Site 0404)	Kassel	Hessen
Germany	Universitaetsklinikum Koeln ( Site 0413)	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Schleswig-Holstein ( Site 0411)	Luebeck	Schleswig-Holstein
Germany	Klinikum rechts der Isar der Technischen Universitaet ( Site 0409)	Muenchen	Bayern
Germany	Klinikum rechts der Isar der Technischen Universität München-HNO Klinik ( Site 0405)	München	Bayern
Germany	Universitaetsklinikum Tuebingen - Medizinische Klinik ( Site 0401)	Tuebingen	Baden-Wurttemberg
Germany	Universitaetsklinikum Ulm ( Site 0402)	Ulm	Baden-Wurttemberg
Hungary	Eszak-Pesti Centrumkorhaz-Honvedkorhaz ( Site 0453)	Budapest
Hungary	Orszagos Onkologiai Intezet ( Site 0454)	Budapest
Hungary	Pecsi Tudomanyegyetem Onkoterapias Intezet ( Site 0452)	Pecs	Baranya
Hungary	Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0450)	Szolnok	Jasz-Nagykun-Szolnok
Ireland	St. James s Hospital ( Site 0500)	Dublin
Israel	Rambam Health Care Campus-Oncology Division ( Site 0550)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 0554)	Jerusalem
Israel	Rabin Medical Center ( Site 0552)	Petah Tikva
Israel	Chaim Sheba Medical Center. ( Site 0553)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0551)	Tel Aviv
Japan	Hyogo Cancer Center ( Site 0656)	Akashi	Hyogo
Japan	Chiba Cancer Center ( Site 0652)	Chiba
Japan	National Hospital Organization Kyushu Cancer Center ( Site 0660)	Fukuoka
Japan	Hiroshima University Hospital ( Site 0655)	Hiroshima
Japan	National Cancer Center Hospital East ( Site 0661)	Kashiwa	Chiba
Japan	Kagawa University Hospital ( Site 0651)	Kita-gun	Kagawa
Japan	Aichi Cancer Center Hospital ( Site 0658)	Nagoya	Aichi
Japan	National Cancer Center Hospital ( Site 0650)	Tokyo
Japan	Tokyo Medical and Dental University Hospital ( Site 0654)	Tokyo
Japan	Tokyo Medical University Hospital ( Site 0659)	Tokyo
Japan	Yokohama City University Hospital ( Site 0657)	Yokohama	Kanagawa
Korea, Republic of	National Cancer Center ( Site 0702)	Goyang-si	Kyonggi-do
Korea, Republic of	The Catholic University of Korea St. Vincent s Hospital ( Site 0704)	Gyeonggi-do	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 0705)	Hwasun Gun	Jeonranamdo
Korea, Republic of	Seoul National University Bundang Hospital ( Site 0703)	Seongnam-si	Kyonggi-do
Korea, Republic of	Severance Hospital, Yonsei University Health System ( Site 0701)	Seoul
Poland	Szpitale Pomorskie Sp. z o.o. ( Site 0935)	Gdynia	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0901)	Gliwice	Slaskie
Poland	Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0905)	Krakow	Malopolskie
Poland	Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0920)	Lodz	Lodzkie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Portugal	Hospital de Braga ( Site 0951)	Braga
Portugal	CHLN Hospital Santa Maria ( Site 0952)	Lisboa
Portugal	Hospital CUF Descobertas ( Site 0953)	Lisboa
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0950)	Porto
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1000)	Kazan	Tatarstan, Respublika
Russian Federation	N.N. Blokhin NMRCO ( Site 1005)	Moscow	Moskva
Russian Federation	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1001)	Yaroslavl	Yaroslavskaya Oblast
Spain	Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1204)	Badalona	Barcelona
Spain	Hospital Vall D Hebron ( Site 1200)	Barcelona
Spain	ICO L Hospitalet ( Site 1208)	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitario La Paz ( Site 1201)	Madrid
Spain	Hospital Clinico Universitario de Santiago ( Site 1207)	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Virgen del Rocio ( Site 1206)	Sevilla
Switzerland	Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1921)	Bellinzona	Ticino
Switzerland	Hopitaux Universitaires de Geneve HUG ( Site 1920)	Geneve
Switzerland	Universitaetsspital Zurich ( Site 1923)	Zuerich	Aargau
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1303)	Kaohsiung
Taiwan	Taichung Veterans General Hospital ( Site 1301)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 1302)	Tainan
Taiwan	National Taiwan University Hospital ( Site 1300)	Taipei
Ukraine	Clinical oncology dispensary of Dnipro ( Site 1706)	Dnipro	Dnipropetrovska Oblast
Ukraine	Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1705)	Dnipro	Dnipropetrovska Oblast
Ukraine	Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov ( Site 1709)	Dnipropetrovsk	Dnipropetrovska Oblast
Ukraine	Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1703)	Kapitanivka Village	Kyivska Oblast
Ukraine	Ukrainian Center of Tomotherapy ( Site 1708)	Kropyvnitskiy	Kirovohradska Oblast
Ukraine	PP PPC Acinus Medical and Diagnostic Centre ( Site 1704)	Kropyvnytskyi	Kirovohradska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 1701)	Kyiv
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 1702)	Kyiv	Kyivska Oblast
Ukraine	LISOD. Hospital ( Site 1707)	Pliuty	Kyiv
United Kingdom	Addenbrooke's Hospital ( Site 1610)	Cambridge	Cambridgeshire
United Kingdom	Castle Hill Hospital ( Site 1601)	Cottingham-Hull	Kingston Upon Hull
United Kingdom	Guy s & St Thomas NHS Foundation Trust ( Site 1604)	London	London, City Of
United Kingdom	Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1603)	London	London, City Of
United Kingdom	Royal Marsden Hospital - Fulham Road London ( Site 1609)	London	London, City Of
United Kingdom	Weston Park Hospital ( Site 1607)	Sheffield
United States	The University of New Mexico Comprehensive Cancer Center ( Site 1882)	Albuquerque	New Mexico
United States	University of Colorado Cancer Center ( Site 1838)	Aurora	Colorado
United States	University of Maryland ( Site 2031)	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 2036)	Basking Ridge	New Jersey
United States	St. Luke's University Health Network ( Site 1801)	Bethlehem	Pennsylvania
United States	St. Vincent Healthcare Frontier Cancer Center ( Site 1818)	Billings	Montana
United States	Saint Alphonsus Regional Medical Center ( Site 2021)	Boise	Idaho
United States	Dana Farber Cancer Center ( Site 1873)	Boston	Massachusetts
United States	Montefiore Einstein Center ( Site 2028)	Bronx	New York
United States	Erie County Medical Center ( Site 2047)	Buffalo	New York
United States	University of Vermont Medical Center ( Site 2009)	Burlington	Vermont
United States	Levine Cancer Institute ( Site 2003)	Charlotte	North Carolina
United States	UVA Health System - Emily Couric Cancer Center ( Site 1826)	Charlottesville	Virginia
United States	Rush University Medical Center ( Site 1823)	Chicago	Illinois
United States	University Hospitals ( Site 2032)	Cleveland	Ohio
United States	University of Missouri Hospital-Otolaryngology - Head and Neck Surgery ( Site 2058)	Columbia	Missouri
United States	The Ohio State University ( Site 2012)	Columbus	Ohio
United States	Memorial Sloan-Kettering Cancer Center at Commack ( Site 2038)	Commack	New York
United States	UT Southwestern Medical Center ( Site 1841)	Dallas	Texas
United States	Henry Ford Health System ( Site 1803)	Detroit	Michigan
United States	Karmanos Cancer Institute ( Site 1870)	Detroit	Michigan
United States	Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 2016)	Edina	Minnesota
United States	NorthShore University HealthSystem ( Site 1812)	Evanston	Illinois
United States	Inova Schar Cancer Institute ( Site 2026)	Fairfax	Virginia
United States	Sanford Health Roger Maris Cancer Center ( Site 2034)	Fargo	North Dakota
United States	University of Florida ( Site 1832)	Gainesville	Florida
United States	Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 2041)	Harrison	New York
United States	Moores Cancer Center ( Site 1885)	La Jolla	California
United States	Monter Cancer Center ( Site 2060)	Lake Success	New York
United States	University of Kentucky Chandler Medical Center-Medical Oncology ( Site 2069)	Lexington	Kentucky
United States	University of Southern California Norris Comprehensive Cancer Center ( Site 1850)	Los Angeles	California
United States	Loyola University Medical Center [Maywood, IL] ( Site 1817)	Maywood	Illinois
United States	University of Miami, Sylvester Comprehensive Cancer Center ( Site 2008)	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center- Monmouth ( Site 2039)	Middletown	New Jersey
United States	MSKCC-Bergen ( Site 2037)	Montvale	New Jersey
United States	Henry Joyce Cancer Clinic ( Site 1827)	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey ( Site 2071)	New Brunswick	New Jersey
United States	Ochsner Cancer Institute ( Site 2045)	New Orleans	Louisiana
United States	Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 2014)	New York	New York
United States	Memorial Sloan Kettering Cancer Center ( Site 1857)	New York	New York
United States	Northwell Health Cancer Institute ( Site 2030)	New York	New York
United States	Weill Cornell Medical College ( Site 2050)	New York	New York
United States	Rutgers New Jersey Medical School-department of Hematology oncology ( Site 2053)	Newark	New Jersey
United States	Hoag Memoriall Hospital Presbyterian ( Site 2056)	Newport Beach	California
United States	AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 2054)	Orlando	Florida
United States	Orlando Health Cancer Institute ( Site 2061)	Orlando	Florida
United States	Sidney Kimmel Cancer Center - Jefferson Health ( Site 2059)	Philadelphia	Pennsylvania
United States	Allegheny General Hospital ( Site 1833)	Pittsburgh	Pennsylvania
United States	Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 2022)	Portland	Oregon
United States	Oregon Health Science University ( Site 1871)	Portland	Oregon
United States	Providence Portland Medical Center ( Site 1843)	Portland	Oregon
United States	Beacon Cancer Care ( Site 2052)	Post Falls	Idaho
United States	UC Davis Health System ( Site 1864)	Sacramento	California
United States	Washington University School of Medicine ( Site 1800)	Saint Louis	Missouri
United States	University of Utah, Huntsman Cancer Institute ( Site 1855)	Salt Lake City	Utah
United States	USA Clinical Trials ( Site 2068)	San Antonio	Texas
United States	St. Joseph Heritage Healthcare ( Site 1806)	Santa Rosa	California
United States	Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 1865)	Seattle	Washington
United States	Avera Cancer Institute- Research ( Site 2070)	Sioux Falls	South Dakota
United States	Sanford Cancer Center Oncology Clinic ( Site 1859)	Sioux Falls	South Dakota
United States	Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 1897)	Springfield	Missouri
United States	Stony Brook University ( Site 2063)	Stony Brook	New York
United States	Memorial Sloan Kettering Cancer Center - Nassau ( Site 2040)	Uniondale	New York
United States	George Washington University Medical Faculty Associates ( Site 2035)	Washington	District of Columbia
United States	MedStar Washington Hospital Center ( Site 2062)	Washington	District of Columbia
United States	University of Kansas Cancer Center ( Site 2004)	Westwood	Kansas
United States	Wake Forest Compenhensive Cancer Center ( Site 2029)	Winston-Salem	North Carolina
United States	University of Massachusetts Memorial Medical Center ( Site 1875)	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  France,  Germany,  Hungary,  Ireland,  Israel,  Japan,  Korea, Republic of,  Poland,  Portugal,  Russian Federation,  Spain,  Switzerland,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS)	EFS is the time from the date of randomization to the date of first record of any of the following events: radiographic disease progression; local or distant progression or recurrence as assessed with imaging or biopsy as indicated; or death due to any cause. Radiographic disease progression during neoadjuvant phase that precludes surgery will be considered an event; a secondary malignancy will not be considered an event.	Up to ~80 months
Secondary	Major Pathological Response (mPR)	The percentage of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as =10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.	Up to ~64 months
Secondary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to ~92 months
Secondary	Pathological Complete Response (pCR)	Pathological complete response (pCR) is measured as the percentage of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.	Up to ~64 months
Secondary	Change From Baseline in Global Health Status/Quality of Life Scale (GHS/QoL)	Change from baseline in the combined score of global health status (GHS)/quality of life (QoL) using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 29 and 30. Participant responses to questions regarding overall health/QoL will be scored on a 7-point scale (1=Very poor to 7=Excellent) with a higher score indicating better overall health status.	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary	Change From Baseline in Global Health Status/Physical Functioning Scales	Change from baseline in the combined score of physical functioning scale using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (EORTC QLQ-C30) items 1 through 5. Participant responses to questions regarding their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much) with a higher score indicating worse physical functioning.	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary	Change from Baseline in Swallowing, Speech, and Pain Symptoms	Change from baseline in the combined score of swallowing, speech, and pain symptoms using the European Organization for Research and Treatment of Cancer Head and Neck Questionnaire (EORTC QLQ-H&N35) items 31-38, 46, and 53-54. Participant responses to questions regarding problems with swallowing, speech and pain in the mouth will be scored on a 4-point scale (1=Not at all to 4=Very much) with a higher score indicating more problems.	Prior to the first dose of study therapy (Baseline) and at the time of last follow-up (up to ~92 months)
Secondary	Percentage of Participants Experiencing An Adverse Event (AEs)	Percentage of participants experiencing any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy	From time of first dose of study treatment until the end of follow-up (up to ~92 months)
Secondary	Percentage of Participants Discontinuing Study Drug Due to AEs	Percentage of participants discontinuing study drug due to an AE	From time of first dose of study treatment until the end of treatment (up to 12 months)

External Links

•   Merck Clinical Trial Information
•   Plain Language Summary