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)

NCT03765918 | Active Not Recruiting Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-689MK-3475-6892022-500254-41-00U1111-1274-23982017-001139-38
• Study Type: interventional
• Target: 714
• Locations: 23 countries
• Sites: 188

Brief Summary

This is a randomized, active-controlled, open-label study of pembrolizumab 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.

Conditions

Head and Neck Neoplasms

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 (3)

• Event-free Survival (EFS)

  EFS was based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) and was defined as the time from randomization to any of the following events: radiographic disease progression (RDP; participants who undergo a definitive biopsy of the progressed lesion and are found to have no histologic evidence of invasive cancer will not meet criteria for an event), RDP during the neoadjuvant phase that precluded surgery, local or distant disease progression or recurrence (as assessed with imaging or biopsy as indicated), or death due to any cause. A secondary malignancy was not considered an EFS event. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, EFS per RECIST 1.1 as assessed by BICR in all randomized participants was presented.

  Up to ~66 months

• EFS in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10

  EFS was based on RECIST 1.1 as assessed by BICR and was defined as the time from randomization to any of the following events: RDP (participants who undergo a definitive biopsy of the progressed lesion and are found to have no histologic evidence of invasive cancer will not meet criteria for an event), RDP during the neoadjuvant phase that precluded surgery, local or distant disease progression or recurrence (as assessed with imaging or biopsy as indicated), or death due to any cause. A secondary malignancy was not considered an EFS event. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, EFS per RECIST 1.1 as assessed by BICR in participants with PD-L1 CPS ≥10 was presented.

  Up to ~66 months

• EFS in Participants With PD-L1 CPS ≥1

  EFS was based on RECIST 1.1 as assessed by BICR and was defined as the time from randomization to any of the following events: RDP (participants who undergo a definitive biopsy of the progressed lesion and are found to have no histologic evidence of invasive cancer will not meet criteria for an event), RDP during the neoadjuvant phase that precluded surgery, local or distant disease progression or recurrence (as assessed with imaging or biopsy as indicated), or death due to any cause. A secondary malignancy was not considered an EFS event. Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, EFS per RECIST 1.1 as assessed by BICR in participants with PD-L1 CPS ≥1 was presented.

  Up to ~66 months

Secondary Outcomes (71)

• Major Pathological Response (mPR) Rate

  Up to ~66 months

• mPR Rate in Participants With PD-L1 CPS ≥10

  Up to ~66 months

• mPR Rate in Participants With PD-L1 CPS ≥1

  Up to ~66 months

• Pathological Complete Response (pCR) Rate

  Up to ~66 months

• pCR Rate in Participants With PD-L1 CPS ≥10

  Up to ~66 months

Study Arms (2)

Pembrolizumab + Standard of Care (SOC)

EXPERIMENTAL

Neoadjuvant treatment: Participants received 200 mg pembrolizumab by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles (up to 6 weeks) prior to surgery. Adjuvant treatment: Following surgical resection, participants received 200 mg pembrolizumab, IV infusion, on Day 1 of a 21-day cycle for 15 cycles (up to 45 weeks) plus investigator's choice of SOC treatment regimen consisting of radiotherapy, with or without cisplatin 100 mg/m\^2, IV infusion, on Day 1 of a 21-day cycle for 3 cycles (up to 9 weeks).

Biological: Pembrolizumab 200 mg; Radiation: Radiotherapy 60 Gray; Radiation: Radiotherapy 66 Gray; Radiation: Radiotherapy 70 Gray; Drug: Cisplatin 100 mg/m^2

Standard of Care (SOC)

ACTIVE COMPARATOR

Adjuvant treatment: Following surgical resection, participants received investigator's choice of SOC treatment regimen consisting of radiotherapy, with or without cisplatin 100 mg/m\^2, IV infusion, on Day 1 of a 21-day cycle for 3 cycles (up to 9 weeks).

Radiation: Radiotherapy 60 Gray; Radiation: Radiotherapy 66 Gray; Radiation: Radiotherapy 70 Gray; Drug: Cisplatin 100 mg/m^2

Interventions

Pembrolizumab 200 mg BIOLOGICAL

200 mg administered IV infusion on Day 1 of each 21-day cycle

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + Standard of Care (SOC)

Radiotherapy 60 Gray RADIATION

Low risk participants administered 2 Gray in 30 fractions. Administered using intensity modulated radiation therapy.

Pembrolizumab + Standard of Care (SOC); Standard of Care (SOC)

Radiotherapy 66 Gray RADIATION

High risk participants administered 2 Gray in 33 fractions. Administered using intensity modulated radiation therapy.

Pembrolizumab + Standard of Care (SOC); Standard of Care (SOC)

Radiotherapy 70 Gray RADIATION

Participants with gross residual disease administered 2 Gray in 35 fractions. Administered using intensity modulated radiation therapy.

Pembrolizumab + Standard of Care (SOC); Standard of Care (SOC)

Cisplatin 100 mg/m^2 DRUG

100 mg/m\^2 administered by IV infusion on Day 1 of each 21-day cycle

Also known as: Platinol®, Platinol-AQ®

Pembrolizumab + Standard of Care (SOC); Standard of Care (SOC)

Eligibility Criteria

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

You may qualify if:

• 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 Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 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

You may not qualify if:

• Has Stage T4B and/or N3 locoregionally advanced head and neck squamous cell carcinoma (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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (192)

Moores Cancer Center ( Site 1885)

La Jolla, California, 92093-0698, United States

Location

University of Southern California Norris Comprehensive Cancer Center ( Site 1850)

Los Angeles, California, 90033, United States

Location

Hoag Memoriall Hospital Presbyterian ( Site 2056)

Newport Beach, California, 92688, United States

Location

UC Davis Health System ( Site 1864)

Sacramento, California, 95817, United States

Location

St. Joseph Heritage Healthcare ( Site 1806)

Santa Rosa, California, 95403, United States

Location

University of Colorado Cancer Center ( Site 1838)

Aurora, Colorado, 80045, United States

Location

MedStar Washington Hospital Center ( Site 2062)

Washington D.C., District of Columbia, 20010, United States

Location

George Washington University Medical Faculty Associates ( Site 2035)

Washington D.C., District of Columbia, 20037, United States

Location

University of Florida ( Site 1832)

Gainesville, Florida, 32608, United States

Location

University of Miami, Sylvester Comprehensive Cancer Center ( Site 2008)

Miami, Florida, 33136, United States

Location

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 2054)

Orlando, Florida, 32804, United States

Location

Orlando Health Cancer Institute ( Site 2061)

Orlando, Florida, 32806, United States

Location

Saint Alphonsus Regional Medical Center ( Site 2021)

Boise, Idaho, 83706, United States

Location

Beacon Cancer Care ( Site 2052)

Post Falls, Idaho, 83854, United States

Location

Rush University Medical Center ( Site 1823)

Chicago, Illinois, 60607, United States

Location

NorthShore University HealthSystem ( Site 1812)

Evanston, Illinois, 60201, United States

Location

Loyola University Medical Center [Maywood, IL] ( Site 1817)

Maywood, Illinois, 60153, United States

Location

University of Kansas Cancer Center ( Site 2004)

Westwood, Kansas, 66205, United States

Location

University of Kentucky Chandler Medical Center-Medical Oncology ( Site 2069)

Lexington, Kentucky, 40536, United States

Location

Ochsner Cancer Institute ( Site 2045)

New Orleans, Louisiana, 70121, United States

Location

University of Maryland ( Site 2031)

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Center ( Site 1873)

Boston, Massachusetts, 02215, United States

Location

University of Massachusetts Memorial Medical Center ( Site 1875)

Worcester, Massachusetts, 01655, United States

Location

Karmanos Cancer Institute ( Site 1870)

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System ( Site 1803)

Detroit, Michigan, 48202, United States

Location

Southdale Cancer Care, University of Minnesota Medical Center- Edina ( Site 2016)

Edina, Minnesota, 55435, United States

Location

University of Missouri Hospital-Otolaryngology - Head and Neck Surgery ( Site 2058)

Columbia, Missouri, 65212, United States

Location

Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 1897)

Springfield, Missouri, 65804, United States

Location

Washington University School of Medicine ( Site 1800)

St Louis, Missouri, 63110, United States

Location

St. Vincent Healthcare Frontier Cancer Center ( Site 1818)

Billings, Montana, 59102, United States

Location

Memorial Sloan Kettering Cancer Center Basking Ridge ( Site 2036)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Cancer Center- Monmouth ( Site 2039)

Middletown, New Jersey, 07748, United States

Location

MSKCC-Bergen ( Site 2037)

Montvale, New Jersey, 07645, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 2071)

New Brunswick, New Jersey, 08901, United States

Location

Rutgers New Jersey Medical School-department of Hematology oncology ( Site 2053)

Newark, New Jersey, 07103, United States

Location

The University of New Mexico Comprehensive Cancer Center ( Site 1882)

Albuquerque, New Mexico, 87131-0001, United States

Location

Erie County Medical Center ( Site 2047)

Buffalo, New York, 14215, United States

Location

Memorial Sloan-Kettering Cancer Center at Commack ( Site 2038)

Commack, New York, 11725, United States

Location

Memorial Sloan-Kettering Cancer Center at West Harrison ( Site 2041)

Harrison, New York, 10604, United States

Location

Monter Cancer Center ( Site 2060)

Lake Success, New York, 11042, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 2014)

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center ( Site 1857)

New York, New York, 10065, United States

Location

Weill Cornell Medical College ( Site 2050)

New York, New York, 10065, United States

Location

Northwell Health Cancer Institute ( Site 2030)

New York, New York, 10075, United States

Location

Stony Brook University ( Site 2063)

Stony Brook, New York, 11794, United States

Location

Montefiore Einstein Center ( Site 2028)

The Bronx, New York, 10467, United States

Location

Memorial Sloan Kettering Cancer Center - Nassau ( Site 2040)

Uniondale, New York, 11553, United States

Location

Levine Cancer Institute ( Site 2003)

Charlotte, North Carolina, 28204, United States

Location

Wake Forest Compenhensive Cancer Center ( Site 2029)

Winston-Salem, North Carolina, 27357, United States

Location

Sanford Health Roger Maris Cancer Center ( Site 2034)

Fargo, North Dakota, 58122, United States

Location

University Hospitals ( Site 2032)

Cleveland, Ohio, 44106, United States

Location

The Ohio State University ( Site 2012)

Columbus, Ohio, 43210, United States

Location

Providence Portland Medical Center ( Site 1843)

Portland, Oregon, 97220, United States

Location

Kaiser Permanente Center for Health Research-Kaiser Permanente Medical Center ( Site 2022)

Portland, Oregon, 97227, United States

Location

Oregon Health Science University ( Site 1871)

Portland, Oregon, 97239, United States

Location

St. Luke's University Health Network ( Site 1801)

Bethlehem, Pennsylvania, 18015, United States

Location

Sidney Kimmel Cancer Center - Jefferson Health ( Site 2059)

Philadelphia, Pennsylvania, 19107, United States

Location

Allegheny General Hospital ( Site 1833)

Pittsburgh, Pennsylvania, 15212, United States

Location

Sanford Cancer Center Oncology Clinic ( Site 1859)

Sioux Falls, South Dakota, 57104, United States

Location

Avera Cancer Institute- Research ( Site 2070)

Sioux Falls, South Dakota, 57105, United States

Location

Henry Joyce Cancer Clinic ( Site 1827)

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center ( Site 1841)

Dallas, Texas, 75390, United States

Location

USA Clinical Trials ( Site 2068)

San Antonio, Texas, 78229, United States

Location

University of Utah, Huntsman Cancer Institute ( Site 1855)

Salt Lake City, Utah, 84112-5550, United States

Location

University of Vermont Medical Center ( Site 2009)

Burlington, Vermont, 05401, United States

Location

UVA Health System - Emily Couric Cancer Center ( Site 1826)

Charlottesville, Virginia, 22908, United States

Location

Inova Schar Cancer Institute ( Site 2026)

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 1865)

Seattle, Washington, 98109, United States

Location

Hospital Universitario Austral ( Site 0009)

Pilar, Buenos Aires, B1629AHJ, Argentina

Location

Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0019)

Buenos Aires, Buenos Aires F.D., C1431FWO, Argentina

Location

Hospital Britanico de Buenos Aires ( Site 0012)

Ciudad de Buenos Aires, Buenos Aires F.D., C1280AEB, Argentina

Location

Fundacion Estudios Clinicos-Oncology ( Site 0017)

Rosario, Santa Fe Province, 2000, Argentina

Location

Sanatorio Britanico ( Site 0013)

Rosario, Santa Fe Province, S2000CVB, Argentina

Location

Instituto de Oncologia de Rosario ( Site 0002)

Rosario, Santa Fe Province, S2000KZE, Argentina

Location

Hospital Provincial del Centenario ( Site 0008)

Rosario, Santa Fe Province, S2002KDS, Argentina

Location

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0016)

Buenos Aires, 1012, Argentina

Location

Hospital Aleman Buenos Aires Argentina ( Site 0004)

Buenos Aires, C1118AAT, Argentina

Location

Instituto de Oncología Angel Roffo ( Site 0003)

Buenos Aires, C1417DTB, Argentina

Location

CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0010)

San Juan, J5402DIL, Argentina

Location

The Crown Princess Mary Cancer Centre - Westmead Hospital ( Site 0051)

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane and Women s Hospital ( Site 0050)

Herston, Queensland, 4029, Australia

Location

Landeskrankenhaus - Universitatsklinikum Graz ( Site 1902)

Graz, Styria, 8036, Austria

Location

Ordensklinikum Linz Gmbh - Barmherzige Schwestern ( Site 1901)

Linz, Upper Austria, 4010, Austria

Location

Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 1900)

Salzburg, 5020, Austria

Location

Medizinische Universität Wien ( Site 1903)

Vienna, 1090, Austria

Location

Hopital de Jolimont ( Site 0103)

Haine-Saint-Paul, Hainaut, 7100, Belgium

Location

UZ Gent ( Site 0101)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

AZ Nikolaas ( Site 0104)

Sint-Niklaas, Oost-Vlaanderen, 9100, Belgium

Location

Centro Regional Integrado de Oncologia ( Site 0160)

Fortaleza, Ceará, 60336-232, Brazil

Location

Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0155)

Salvador, Estado de Bahia, 40050-410, Brazil

Location

Hospital Marcio Cunha-Unidade de Pesquisa Clínica ( Site 0177)

Ipatinga, Minas Gerais, 35162-189, Brazil

Location

Liga Norte Riograndense Contra o Cancer ( Site 0171)

Natal, Rio Grande do Norte, 59075-740, Brazil

Location

Hospital Nossa Senhora da Conceicao ( Site 0165)

Porto Alegre, Rio Grande do Sul, 91359-200, Brazil

Location

Hospital de Base de Sao Jose de Rio Preto ( Site 0153)

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0169)

Rio de Janeiro, 20231-050, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0167)

São Paulo, 01246-000, Brazil

Location

BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0175)

São Paulo, 01321-001, Brazil

Location

Cross Cancer Institute ( Site 0201)

Edmonton, Alberta, T6G 1Z2, Canada

Location

Sunnybrook Research Institute ( Site 0211)

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Cancer Centre ( Site 0202)

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University Health Centre ( Site 0210)

Montreal, Quebec, H4A 3J1, Canada

Location

CIUSSS de l'Estrie-CHUS ( Site 0209)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Fundacion Arturo Lopez Perez FALP ( Site 0251)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Clinica de la Costa S.A.S. ( Site 0307)

Barranquilla, Atlántico, 080020, Colombia

Location

Centro de Investigacion Clinica del Country ( Site 0304)

Bogotá, Bogota D.C., 110221, Colombia

Location

Oncologos del Occidente S.A. ( Site 0310)

Pereira, Risaralda Department, 661002, Colombia

Location

Centro Medico Imbanaco de Cali S.A ( Site 0300)

Cali, Valle del Cauca Department, 760042, Colombia

Location

Centre Antoine Lacassagne ( Site 0351)

Nice, Alpes-Maritimes, 06189, France

Location

Hopital de la Timone ( Site 0356)

Marseille, Bouches-du-Rhone, 13385, France

Location

Institut Claudius Regaud IUCT Oncopole ( Site 0355)

Toulouse, Haute-Garonne, 31059, France

Location

Institut Gustave Roussy ( Site 0353)

Villejuif, Val-de-Marne, 94800, France

Location

Institut Sainte Catherine ( Site 0352)

Avignon, Vaucluse, 84918, France

Location

Hopital Europeen Georges Pompidou ( Site 0358)

Paris, 75015, France

Location

Institut Curie ( Site 0350)

Paris, 75248, France

Location

Universitaetsklinikum Tuebingen - Medizinische Klinik ( Site 0401)

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Universitaetsklinikum Ulm ( Site 0402)

Ulm, Baden-Wurttemberg, 89075, Germany

Location

Universitaetsklinikum Erlangen-Strahlenklinik ( Site 0412)

Erlangen, Bavaria, 91054, Germany

Location

Klinikum rechts der Isar der Technischen Universitaet ( Site 0409)

Munich, Bavaria, 81675, Germany

Location

Klinikum rechts der Isar der Technischen Universität München-HNO Klinik ( Site 0405)

München, Bavaria, 81675, Germany

Location

Universitaetsklinikum Frankfurt ( Site 0403)

Frankfurt am Main, Hesse, 60590, Germany

Location

Klinikum Kassel GmbH ( Site 0404)

Kassel, Hesse, 34125, Germany

Location

Universitaetsklinikum Koeln ( Site 0413)

Cologne, North Rhine-Westphalia, 50937, Germany

Location

Universitätsklinikum Schleswig-Holstein ( Site 0411)

Lübeck, Schleswig-Holstein, 23538, Germany

Location

SRH Wald-Klinikum Gera GmbH ( Site 0406)

Gera, Thuringia, 07548, Germany

Location

Charite Universitätsmedizin Berlin Campus Benjamin Franklin ( Site 0414)

Berlin, 12203, Germany

Location

Universitaetsklinikum Hamburg Eppendorf ( Site 0407)

Hamburg, 20246, Germany

Location

Pecsi Tudomanyegyetem Onkoterapias Intezet ( Site 0452)

Pécs, Baranya, 7621, Hungary

Location

Jász-Nagykun-Szolnok Vármegyei Hetényi Géza Kórház ( Site 0450)

Szolnok, Jász-Nagykun-Szolnok, 5000, Hungary

Location

Eszak-Pesti Centrumkorhaz-Honvedkorhaz ( Site 0453)

Budapest, 1062, Hungary

Location

Orszagos Onkologiai Intezet ( Site 0454)

Budapest, 1122, Hungary

Location

St. James s Hospital ( Site 0500)

Dublin, Dublin 8, Ireland

Location

Rambam Health Care Campus-Oncology Division ( Site 0550)

Haifa, 3109601, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 0554)

Jerusalem, 9112001, Israel

Location

Rabin Medical Center ( Site 0552)

Petah Tikva, 4963211, Israel

Location

Chaim Sheba Medical Center. ( Site 0553)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 0551)

Tel Aviv, 6423906, Israel

Location

Aichi Cancer Center Hospital ( Site 0658)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 0661)

Kashiwa, Chiba, 277-8577, Japan

Location

Hyogo Cancer Center ( Site 0656)

Akashi, Hyōgo, 673-8558, Japan

Location

Kagawa University Hospital ( Site 0651)

Kita-gun, Kagawa-ken, 761-0793, Japan

Location

Yokohama City University Hospital ( Site 0657)

Yokohama, Kanagawa, 236-0004, Japan

Location

Chiba Cancer Center ( Site 0652)

Chiba, 260-8717, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 0660)

Fukuoka, 811-1395, Japan

Location

Hiroshima University Hospital ( Site 0655)

Hiroshima, 734-8551, Japan

Location

National Cancer Center Hospital ( Site 0650)

Tokyo, 104-0045, Japan

Location

Tokyo Medical and Dental University Hospital ( Site 0654)

Tokyo, 113-8519, Japan

Location

Tokyo Medical University Hospital ( Site 0659)

Tokyo, 160-0023, Japan

Location

Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 0905)

Krakow, Lesser Poland Voivodeship, 31-826, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (

Warsaw, Masovian Voivodeship, 02-781, Poland

Location

Szpitale Pomorskie Sp. z o.o. ( Site 0935)

Gdynia, Pomeranian Voivodeship, 81-159, Poland

Location

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0901)

Gliwice, Silesian Voivodeship, 44101, Poland

Location

Wojewodzki Szpital Specjalistyczny im. M. Kopernika w Lodzi ( Site 0920)

Lodz, Łódź Voivodeship, 93-513, Poland

Location

Hospital de Braga ( Site 0951)

Braga, 4710-243, Portugal

Location

CHLN Hospital Santa Maria ( Site 0952)

Lisbon, 1649-035, Portugal

Location

Hospital CUF Descobertas ( Site 0953)

Lisbon, 1998-018, Portugal

Location

Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0950)

Porto, 4200-072, Portugal

Location

N.N. Blokhin NMRCO ( Site 1005)

Moscow, Moscow, 115522, Russia

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1000)

Kazan', Tatarstan, Respublika, 420029, Russia

Location

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 1001)

Yaroslavl, Yaroslavl Oblast, 150054, Russia

Location

Chonnam National University Hwasun Hospital ( Site 0705)

Hwasun Gun, Jeonranamdo, 58128, South Korea

Location

National Cancer Center ( Site 0702)

Goyang-si, Kyonggi-do, 10408, South Korea

Location

The Catholic University of Korea St. Vincent s Hospital ( Site 0704)

Gyeonggi-do, Kyonggi-do, 16247, South Korea

Location

Seoul National University Bundang Hospital ( Site 0703)

Seongnam-si, Kyonggi-do, 13620, South Korea

Location

Severance Hospital, Yonsei University Health System ( Site 0701)

Seoul, 03722, South Korea

Location

Hospital Germans Trias i Pujol. ICO de Badalona ( Site 1204)

Badalona, Barcelona, 08916, Spain

Location

ICO L Hospitalet ( Site 1208)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Clinico Universitario de Santiago ( Site 1207)

Santiago de Compostela, La Coruna, 15706, Spain

Location

Hospital Vall D Hebron ( Site 1200)

Barcelona, 08035, Spain

Location

Hospital Universitario La Paz ( Site 1201)

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio ( Site 1206)

Seville, 41013, Spain

Location

Universitaetsspital Zurich ( Site 1923)

Zuerich, Canton of Aargau, 8091, Switzerland

Location

Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1921)

Bellinzona, Canton Ticino, 6500, Switzerland

Location

Hopitaux Universitaires de Geneve HUG ( Site 1920)

Geneva, 1211, Switzerland

Location

Chang Gung Medical Foundation. Kaohsiung Branch ( Site 1303)

Kaohsiung City, 833, Taiwan

Location

Taichung Veterans General Hospital ( Site 1301)

Taichung, 40705, Taiwan

Location

National Cheng Kung University Hospital ( Site 1302)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 1300)

Taipei, 10002, Taiwan

Location

Clinical oncology dispensary of Dnipro ( Site 1706)

Dnipro, Dnipropetrovsk Oblast, 49055, Ukraine

Location

Municipal Non-Profit Enterprise City Clinical Hospital 4 of Dnipro City Council ( Site 1705)

Dnipro, Dnipropetrovsk Oblast, 49102, Ukraine

Location

Dnipropetrovsk Regional Hospital n.a. I.I. Mechnikov ( Site 1709)

Dnipropetrovsk, Dnipropetrovsk Oblast, 49005, Ukraine

Location

Ukrainian Center of Tomotherapy ( Site 1708)

Kropyvnitskiy, Kirovohrad Oblast, 25011, Ukraine

Location

PP PPC Acinus Medical and Diagnostic Centre ( Site 1704)

Kropyvnytskyi, Kirovohrad Oblast, 25006, Ukraine

Location

LISOD. Hospital ( Site 1707)

Pliuty, Kyiv Oblast, 08720, Ukraine

Location

Medical Center of Yuriy Spizhenko LLC.-Clinical Trial ( Site 1703)

Kapitanivka Village, Kyivska Oblast, 08111, Ukraine

Location

National Cancer Institute of the MoH of Ukraine ( Site 1702)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

Kyiv City Clinical Oncology Centre ( Site 1701)

Kyiv, 03115, Ukraine

Location

Addenbrooke's Hospital ( Site 1610)

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

Castle Hill Hospital ( Site 1601)

Cottingham-Hull, Kingston Upon Hull, HU16 5JQ, United Kingdom

Location

Guy s & St Thomas NHS Foundation Trust ( Site 1604)

London, London, City of, SE1 9RT, United Kingdom

Location

Royal Marsden Hospital - Fulham Road London ( Site 1609)

London, London, City of, SW3 6JJ, United Kingdom

Location

Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1603)

London, London, City of, W6 8RF, United Kingdom

Location

Weston Park Hospital ( Site 1607)

Sheffield, S10 2SJ, United Kingdom

Location

Related Publications (1)

• Uppaluri R, Haddad RI, Tao Y, Le Tourneau C, Lee NY, Westra W, Chernock R, Tahara M, Harrington KJ, Klochikhin AL, Brana I, Vasconcelos Alves G, Hughes BGM, Oliva M, Pinto Figueiredo Lima I, Ueda T, Rutkowski T, Schroeder U, Mauz PS, Fuereder T, Laban S, Oridate N, Popovtzer A, Mach N, Korobko Y, Costa DA, Hooda-Nehra A, Rodriguez CP, Bell RB, Manschot C, Benjamin K, Gumuscu B, Adkins D; KEYNOTE-689 Investigators. Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer. N Engl J Med. 2025 Jul 3;393(1):37-50. doi: 10.1056/NEJMoa2415434. Epub 2025 Jun 18.

  PMID: 40532178 DERIVED

Related Links

• Merck Clinical Trial Information
• Plain Language Summary

MeSH Terms

Conditions

Head and Neck Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Cisplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Results Point of Contact

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

ClinicalTrialsDisclosure@msd.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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2018
• First Posted: December 5, 2018
• Study Start: December 17, 2018
• Primary Completion: July 25, 2024
• Study Completion (Estimated): September 10, 2026
• Last Updated: August 20, 2025
• Results First Posted: August 20, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

IL (5); CO (4); IE (1); AR (11); CL (1); AU (2); PL (5); PT (4); US (68); BR (9); RU (3); KR (5); BE (3); UA (9); JP (11); ES (6); HU (4); GB (6); CH (3); CA (5); FR (7); DE (12); TW (4)