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
About this trial
This is an interventional treatment trial for Head and Neck Neoplasms focused on measuring 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)
Eligibility Criteria
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
Sites / Locations
- Moores Cancer Center ( Site 1885)
- University of Southern California Norris Comprehensive Cancer Center ( Site 1850)
- Hoag Memoriall Hospital Presbyterian ( Site 2056)
- UC Davis Health System ( Site 1864)
- St. Joseph Heritage Healthcare ( Site 1806)
- University of Colorado Cancer Center ( Site 1838)
- MedStar Washington Hospital Center ( Site 2062)
- George Washington University Medical Faculty Associates ( Site 2035)
- University of Florida ( Site 1832)
- University of Miami, Sylvester Comprehensive Cancer Center ( Site 2008)
- AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 2054)
- Orlando Health Cancer Institute ( Site 2061)
- Saint Alphonsus Regional Medical Center ( Site 2021)
- Beacon Cancer Care ( Site 2052)
- Rush University Medical Center ( Site 1823)
- NorthShore University HealthSystem ( Site 1812)
- Loyola University Medical Center [Maywood, IL] ( Site 1817)
- University of Kansas Cancer Center ( Site 2004)
- University of Kentucky Chandler Medical Center-Medical Oncology ( Site 2069)
- Ochsner Cancer Institute ( Site 2045)
- University of Maryland ( Site 2031)
- Dana Farber Cancer Center ( Site 1873)
- University of Massachusetts Memorial Medical Center ( Site 1875)
- Karmanos Cancer Institute ( Site 1870)
- Henry Ford Health System ( Site 1803)
- Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 2016)
- University of Missouri Hospital-Otolaryngology - Head and Neck Surgery ( Site 2058)
- Washington University School of Medicine ( Site 1800)
- Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 1897)
- St. Vincent Healthcare Frontier Cancer Center ( Site 1818)
- Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 2036)
- Memorial Sloan Kettering Cancer Center- Monmouth ( Site 2039)
- MSKCC-Bergen ( Site 2037)
- Rutgers Cancer Institute of New Jersey ( Site 2071)
- Rutgers New Jersey Medical School-department of Hematology oncology ( Site 2053)
- The University of New Mexico Comprehensive Cancer Center ( Site 1882)
- Montefiore Einstein Center ( Site 2028)
- Erie County Medical Center ( Site 2047)
- Memorial Sloan-Kettering Cancer Center at Commack ( Site 2038)
- Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 2041)
- Monter Cancer Center ( Site 2060)
- Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 2014)
- Memorial Sloan Kettering Cancer Center ( Site 1857)
- Weill Cornell Medical College ( Site 2050)
- Northwell Health Cancer Institute ( Site 2030)
- Stony Brook University ( Site 2063)
- Memorial Sloan Kettering Cancer Center - Nassau ( Site 2040)
- Levine Cancer Institute ( Site 2003)
- Wake Forest Compenhensive Cancer Center ( Site 2029)
- Sanford Health Roger Maris Cancer Center ( Site 2034)
- University Hospitals ( Site 2032)
- The Ohio State University ( Site 2012)
- Providence Portland Medical Center ( Site 1843)
- Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 2022)
- Oregon Health Science University ( Site 1871)
- St. Luke's University Health Network ( Site 1801)
- Sidney Kimmel Cancer Center - Jefferson Health ( Site 2059)
- Allegheny General Hospital ( Site 1833)
- Sanford Cancer Center Oncology Clinic ( Site 1859)
- Avera Cancer Institute- Research ( Site 2070)
- Henry Joyce Cancer Clinic ( Site 1827)
- UT Southwestern Medical Center ( Site 1841)
- USA Clinical Trials ( Site 2068)
- University of Utah, Huntsman Cancer Institute ( Site 1855)
- University of Vermont Medical Center ( Site 2009)
- UVA Health System - Emily Couric Cancer Center ( Site 1826)
- Inova Schar Cancer Institute ( Site 2026)
- Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 1865)
- Hospital Universitario Austral ( Site 0009)
- Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0019)
- Hospital Britanico de Buenos Aires ( Site 0012)
- Fundacion Estudios Clinicos-Oncology ( Site 0017)
- Sanatorio Britanico ( Site 0013)
- Instituto de Oncologia de Rosario ( Site 0002)
- Hospital Provincial del Centenario ( Site 0008)
- IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0016)
- Hospital Aleman Buenos Aires Argentina ( Site 0004)
- Instituto de Oncología Angel Roffo ( Site 0003)
- CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0010)
- The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 0051)
- Royal Brisbane and Women s Hospital ( Site 0050)
- Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 1901)
- Landeskrankenhaus - Universitatsklinikum Graz ( Site 1902)
- Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 1900)
- Medizinische Universität Wien ( Site 1903)
- Hopital de Jolimont ( Site 0103)
- UZ Gent ( Site 0101)
- AZ Nikolaas ( Site 0104)
- Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0155)
- Centro Regional Integrado de Oncologia ( Site 0160)
- Hospital Marcio Cunha-Unidade de Pesquisa Clínica ( Site 0177)
- Liga Norte Riograndense Contra o Cancer ( Site 0171)
- Hospital Nossa Senhora da Conceicao ( Site 0165)
- Hospital de Base de Sao Jose de Rio Preto ( Site 0153)
- Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0169)
- Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0167)
- BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0175)
- Cross Cancer Institute ( Site 0201)
- Sunnybrook Research Institute ( Site 0211)
- Princess Margaret Cancer Centre ( Site 0202)
- McGill University Health Centre ( Site 0210)
- CIUSSS de l'Estrie-CHUS ( Site 0209)
- Fundacion Arturo Lopez Perez FALP ( Site 0251)
- Clinica de la Costa S.A.S. ( Site 0307)
- Centro de Investigacion Clinica del Country ( Site 0304)
- Oncologos del Occidente S.A. ( Site 0310)
- Centro Medico Imbanaco de Cali S.A ( Site 0300)
- Centre Antoine Lacassagne ( Site 0351)
- Hopital de la Timone ( Site 0356)
- Institut Claudius Regaud IUCT Oncopole ( Site 0355)
- Institut Gustave Roussy ( Site 0353)
- Institut Sainte Catherine ( Site 0352)
- Hopital Europeen Georges Pompidou ( Site 0358)
- Institut Curie ( Site 0350)
- Universitaetsklinikum Tuebingen - Medizinische Klinik ( Site 0401)
- Universitaetsklinikum Ulm ( Site 0402)
- Universitaetsklinikum Erlangen-Strahlenklinik ( Site 0412)
- Klinikum rechts der Isar der Technischen Universitaet ( Site 0409)
- Klinikum rechts der Isar der Technischen Universität München-HNO Klinik ( Site 0405)
- Universitaetsklinikum Frankfurt ( Site 0403)
- Klinikum Kassel GmbH ( Site 0404)
- Universitaetsklinikum Koeln ( Site 0413)
- Universitätsklinikum Schleswig-Holstein ( Site 0411)
- SRH Wald-Klinikum Gera GmbH ( Site 0406)
- Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 0414)
- Universitaetsklinikum Hamburg Eppendorf ( Site 0407)
- Pecsi Tudomanyegyetem Onkoterapias Intezet ( Site 0452)
- Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0450)
- Eszak-Pesti Centrumkorhaz-Honvedkorhaz ( Site 0453)
- Orszagos Onkologiai Intezet ( Site 0454)
- St. James s Hospital ( Site 0500)
- Rambam Health Care Campus-Oncology Division ( Site 0550)
- Hadassah Medical Center. Ein Kerem ( Site 0554)
- Rabin Medical Center ( Site 0552)
- Chaim Sheba Medical Center. ( Site 0553)
- Sourasky Medical Center ( Site 0551)
- Aichi Cancer Center Hospital ( Site 0658)
- National Cancer Center Hospital East ( Site 0661)
- Hyogo Cancer Center ( Site 0656)
- Kagawa University Hospital ( Site 0651)
- Yokohama City University Hospital ( Site 0657)
- Chiba Cancer Center ( Site 0652)
- National Hospital Organization Kyushu Cancer Center ( Site 0660)
- Hiroshima University Hospital ( Site 0655)
- National Cancer Center Hospital ( Site 0650)
- Tokyo Medical and Dental University Hospital ( Site 0654)
- Tokyo Medical University Hospital ( Site 0659)
- Chonnam National University Hwasun Hospital ( Site 0705)
- National Cancer Center ( Site 0702)
- The Catholic University of Korea St. Vincent s Hospital ( Site 0704)
- Seoul National University Bundang Hospital ( Site 0703)
- Severance Hospital, Yonsei University Health System ( Site 0701)
- Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0920)
- Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0905)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
- Szpitale Pomorskie Sp. z o.o. ( Site 0935)
- Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0901)
- Hospital de Braga ( Site 0951)
- CHLN Hospital Santa Maria ( Site 0952)
- Hospital CUF Descobertas ( Site 0953)
- Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0950)
- N.N. Blokhin NMRCO ( Site 1005)
- Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1000)
- Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1001)
- Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1204)
- ICO L Hospitalet ( Site 1208)
- Hospital Clinico Universitario de Santiago ( Site 1207)
- Hospital Vall D Hebron ( Site 1200)
- Hospital Universitario La Paz ( Site 1201)
- Hospital Universitario Virgen del Rocio ( Site 1206)
- Universitaetsspital Zurich ( Site 1923)
- Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1921)
- Hopitaux Universitaires de Geneve HUG ( Site 1920)
- Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1303)
- Taichung Veterans General Hospital ( Site 1301)
- National Cheng Kung University Hospital ( Site 1302)
- National Taiwan University Hospital ( Site 1300)
- Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov ( Site 1709)
- Clinical oncology dispensary of Dnipro ( Site 1706)
- Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1705)
- Ukrainian Center of Tomotherapy ( Site 1708)
- PP PPC Acinus Medical and Diagnostic Centre ( Site 1704)
- Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1703)
- National Cancer Institute of the MoH of Ukraine ( Site 1702)
- LISOD. Hospital ( Site 1707)
- Kyiv City Clinical Oncology Centre ( Site 1701)
- Addenbrooke's Hospital ( Site 1610)
- Castle Hill Hospital ( Site 1601)
- Guy s & St Thomas NHS Foundation Trust ( Site 1604)
- Royal Marsden Hospital - Fulham Road London ( Site 1609)
- Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1603)
- Weston Park Hospital ( Site 1607)
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Pembro Neoadjuvant+Pembro SOC Adjuvant
No Neoadjuvant+SOC Adjuvant
Participants receive 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles as a neoadjuvant prior to surgery. Following surgical resection, high risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 every 3 weeks (Q3W) for fifteen 21-day cycles plus standard of care radiotherapy plus cisplatin 100 mg/m^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive 200 mg pembrolizumab by IV infusion administered on Day 1 Q3W for fifteen 21-day cycles plus standard of care radiotherapy as adjuvant therapy.
Participants receive no neoadjuvant prior to surgery. Following surgical resection, high risk participants receive standard of care radiotherapy plus cisplatin 100 mg/m^2 by IV infusion on Day 1 Q3W for three 21-day cycles as adjuvant therapy. Following surgical resection, low risk participants receive standard of care radiotherapy as adjuvant therapy.