AzTrials
AzTrials

Head and Neck NeoplasmsPhase 3NCT03040999

Study of Pembrolizumab (MK-3475) or Placebo With Chemoradiation in Participants With Locally Advanced Head and Neck Squamous Cell Carcinoma (MK-3475-412/KEYNOTE-412)

A Phase 3 study testing Pembrolizumab, Cisplatin and Accelerated Fractionation (AFX) Radiotherapy in people with Head and Neck Neoplasms, run by Merck Sharp & Dohme LLC at 151 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine the efficacy and safety of pembrolizumab given concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Neoplasms
What is being tested?
Pembrolizumab, Cisplatin and Accelerated Fractionation (AFX) Radiotherapy
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
804 participants
Where
151 sitesin 21 countries
Study dates
5 Apr 2017to 21 Aug 2024
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has a pathologically proven new diagnosis of oropharyngeal p16 positive, oropharyngeal p16 negative, or larynx/hypopharynx/oral cavity (independent of p16) squamous cell carcinoma. Participants with oral cavity tumors need to have unresectable disease. Participants with multiple synchronous tumors are not eligible for the study.
  • Has provided tissue for Programmed Cell Death Receptor Ligand 1 (PD-L1) biomarker analysis from a core or excisional biopsy. If an excisional or incisional biopsy has been performed, participants remain eligible for the study provided the residual disease meets the staging criteria required for the trial (e.g., excisional biopsy of a lymph node with residual T4 primary). Prior surgical debulking, including tonsillectomy, for the head and neck cancer under study is not allowed.
  • Has evaluable tumor burden (measurable and/or non-measurable tumor lesions) assessed by computed tomography scan or magnetic resonance imaging, based on RECIST version 1.1
  • Is eligible for definitive CRT and not considered for primary surgery based on investigator decision
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days prior to receiving the first dose of study therapy
  • Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
  • 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

Who cannot join

  • Is currently participating or has participated in a study with an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy
  • Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-PD-L1, anti-Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in clinical studies with pembrolizumab
  • Has received a live vaccine within 30 days prior to the first dose of study therapy
  • 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
  • Has had prior systemic therapy, targeted therapy, radiotherapy treatment or radical surgery for head and neck cancer under study
  • Has not recovered from major surgery prior to starting study therapy
Show all 17Show fewer
  • Has known active Hepatitis B or C
  • Has known history of Human Immunodeficiency Virus (HIV)
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy is not considered a form of systemic treatment.
  • Has history of a diagnosed and/or treated hematologic or primary solid tumor malignancy, unless in remission for at least 5 years prior to randomization
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has had previous allogeneic tissue/solid organ transplant
  • Has active infection requiring systemic therapy
  • Has a history of severe hypersensitivity reaction to pembrolizumab, Cisplatin or radiotherapy or their analogs
  • Is pregnant or breast feeding or expecting to conceive or father children throughout the study period and for up to 180 days after the last dose of study therapy

Trial locations and contacts

151 sites in 21 countries.

151 sites in 21 countries

United States24 sites

  • University of Michigan Hospital and Health Systems ( Site 0267)

    Ann Arbor, Michigan, 48109

  • Texas Oncology-Arlington North ( Site 8005)

    Arlington, Texas, 76014

  • Texas Oncology-Austin Central ( Site 8002)

    Austin, Texas, 78731

  • Mary Bird Perkins Cancer Center at St. Tammany Parish Hospital ( Site 0281)

    Baton Rouge, Louisiana, 70809

  • St. Vincent Healthcare Frontier Cancer Center ( Site 0286)

    Billings, Montana, 59102

  • University of Virginia Health System ( Site 0261)

    Charlottesville, Virginia, 22908

  • Rush University Medical Center ( Site 0260)

    Chicago, Illinois, 60612

  • Oncology Hematology Care, Inc. ( Site 8003)

    Cincinnati, Ohio, 45242

  • Barbara Ann Karmanos Cancer Institute ( Site 0272)

    Detroit, Michigan, 48201

  • St. Luke's Cancer Center - Anderson ( Site 0251)

    Easton, Pennsylvania, 18045

  • Willamette Valley Cancer Institute and Research Center ( Site 8000)

    Eugene, Oregon, 97401

  • St. Francis Hospital Cancer Center ( Site 1461)

    Greenville, South Carolina, 29607

  • Indiana University ( Site 0264)

    Indianapolis, Indiana, 46202

  • Comprehensive Cancer Centers of Nevada ( Site 8004)

    Las Vegas, Nevada, 89169

  • Texas Oncology PA ( Site 8001)

    Longview, Texas, 75601

  • UCLA Medical Center ( Site 0273)

    Los Angeles, California, 90095

  • Smilow Cancer Hospital at Yale New Haven ( Site 0256)

    New Haven, Connecticut, 06510

  • University of Rochester - James P. Wilmot Cancer Center ( Site 0255)

    Rochester, New York, 14642

  • University of California San Francisco ( Site 0274)

    San Francisco, California, 94115

  • St. Joseph Heritage Healthcare ( Site 0254)

    Santa Rosa, California, 95403

  • Seattle Cancer Care Alliance/Univ of Washington Medical Center ( Site 0269)

    Seattle, Washington, 98109

  • Medical Oncology Associates (Summit Cancer Centers) ( Site 0257)

    Spokane, Washington, 99208

  • Mercy Clinic Cancer and Hematology - Chub O'Reilly Cancer Center ( Site 0290)

    Springfield, Missouri, 65804

  • University of Massachusetts Memorial Medical Center ( Site 0285)

    Worcester, Massachusetts, 01655

Other trials in United States

Japan10 sites

  • Hyogo Cancer Center ( Site 0354)

    Akashi, Hyōgo, 673-8558

  • Chiba Cancer Center ( Site 0358)

    Chiba, 260-8717

  • Hiroshima University Hospital ( Site 0352)

    Hiroshima, 734-8551

  • National Cancer Center Hospital East ( Site 0350)

    Kashiwa, Chiba, 277-8577

  • Kagawa University Hospital ( Site 0359)

    Kita-gun, Kagawa-ken, 761-0793

  • Miyagi Cancer Center ( Site 0353)

    Natori-shi, Miyagi, 981-1293

  • Osaka International Cancer Institute ( Site 0355)

    Osaka, 541-8567

  • Hokkaido University Hospital ( Site 0351)

    Sapporo, Hokkaido, 060-8648

  • Medical Hospital, Tokyo Medical And Dental University ( Site 0356)

    Tokyo, 113-8519

  • The Cancer Institute Hospital of JFCR ( Site 0357)

    Tokyo, 135-8550

Other trials in Japan

Brazil9 sites

  • Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0003)

    Barretos, São Paulo, 14784-400

  • Centro Regional Integrado de Oncologia ( Site 0002)

    Fortaleza, Ceará, 60336-045

  • Liga Norte Riograndense Contra o Cancer ( Site 0005)

    Natal, Rio Grande do Norte, 59075-740

  • Hospital de Clinicas de Porto Alegre ( Site 0011)

    Porto Alegre, Rio Grande do Sul, 90035-903

  • Hospital Nossa Senhora da Conceicao ( Site 0001)

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Hospital das Clinicas da FMUSP de Ribeirao Preto ( Site 0008)

    Ribeirão Preto, 14048-900

  • Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0010)

    Rio de Janeiro, 20230-130

  • Hospital Santa Izabel - Santa Casa de Misericordia da Bahia ( Site 0006)

    Salvador, Estado de Bahia, 40050-410

  • Instituto do Cancer de Sao Paulo - ICESP ( Site 0004)

    São Paulo, São Paulo, 01246-000

Other trials in Brazil

United Kingdom9 sites

  • Ipswich Hospital ( Site 1207)

    Ipswich, Suffolk, IP4 5PD

  • St Bartholomew s Hospital ( Site 1205)

    London, EC1A 7BE

  • The Royal Marsden Foundation Trust ( Site 1200)

    London, SW3 6JJ

  • Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 1204)

    London, W6 8RF

  • Norfolk & Norwich University Hospital NHS Foundation Trust ( Site 1206)

    Norwich, Norfolk, NR4 7UY

  • Lancashire Teaching Hospitals NHS Foundation Trust ( Site 1208)

    Preston, PR2 9HT

  • University Hospital Southampton NHS Foundation Trust ( Site 1203)

    Southampton, SO16 6YD

  • University Hospital of North Staffordshire ( Site 1202)

    Stoke-on-Trent, Staffordshire, ST4 6QG

  • Royal Marsden NHS Foundation Trust ( Site 1201)

    Sutton, SM2 5PT

Other trials in United Kingdom

Canada8 sites

  • Tom Baker Cancer Centre ( Site 0063)

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute ( Site 0064)

    Edmonton, Alberta, T6G 1Z2

  • Juravinski Cancer Centre ( Site 0062)

    Hamilton, Ontario, L8V 5C2

  • London Health Sciences Centre ( Site 0055)

    London, Ontario, N6A 4L6

  • McGill University Health Centre ( Site 0061)

    Montreal, Quebec, H4A 3J1

  • The Ottawa Hospital - Cancer Care ( Site 0052)

    Ottawa, Ontario, K1H 8L6

  • CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0057)

    Sherbrooke, Quebec, J1H 5N4

  • Princess Margaret Cancer Centre ( Site 0051)

    Toronto, Ontario, M5G 1X5

Other trials in Canada

Italy8 sites

  • Azienda Ospedaliero Universitaria Careggi ( Site 0955)

    Florence, 50134

  • Istituto Nazionale Tumori ( Site 0950)

    Milan, 20133

  • Istituto Europeo di Oncologia ( Site 0953)

    Milan, 20141

  • Azienda Ospedaliera San Paolo ( Site 0952)

    Milan, 20142

  • Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0954)

    Modena, MO, 41124

  • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 0951)

    Naples, 80121

  • Istituto Oncologico Veneto ( Site 0957)

    Padova, 35128

  • Fondazione IRCCS - Policlinico San Matteo ( Site 0960)

    Pavia, 27100

Other trials in Italy

Poland8 sites

  • Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1005)

    Bielsko-Biala, 43-300

  • Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1007)

    Gdynia, 81-519

  • Centrum Onkologii. Instytut im. Marii Sklodowskiej-Curie ( Site 1010)

    Gliwice, 44-101

  • Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie ( Site 1008)

    Krakow, 31-826

  • Zachodniopomorskie Centrum Onkologii ( Site 1013)

    Szczecin, 71-730

  • Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie ( Site 1000)

    Warsaw, 02-781

  • Mazowiecki Szpital Onkologiczny ( Site 1015)

    Wieliszew, Masovian Voivodeship, 05-135

  • Dolnoslaskie Centrum Onkologii. ( Site 1001)

    Wroclaw, Lower Silesian Voivodeship, 53-413

Other trials in Poland

Turkey (Türkiye)8 sites

  • Basken Adana Dr.Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 1103)

    Adana, 01250

  • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1102)

    Ankara, 06100

  • Ankara Sehir Hastanesi ( Site 1108)

    Ankara, 06800

  • Istanbul Universitesi Istanbul Tip Fakultesi ( Site 1100)

    Istanbul, 34093

  • Medipol Universite Hastanesi ( Site 1104)

    Istanbul, 34214

  • Medical Park Izmir Hastanesi ( Site 1109)

    Izmir, 35520

  • Kocaeli Universitesi Tip Fakultesi ( Site 1106)

    Kocaeli, 41380

  • Inonu Universitesi Tip Fakultesi ( Site 1101)

    Malatya, 44280

Other trials in Turkey (Türkiye)

Germany7 sites

  • Universitätsklinikum Erlangen ( Site 0801)

    Erlangen, 91054

  • SRH Waldklinikum Gera GmbH ( Site 0802)

    Gera, 07548

  • Universitares Cancer Center Hamburg - UCCH ( Site 0811)

    Hamburg, 20246

  • Medizinische Hochschule Hannover ( Site 0807)

    Hanover, 30325

  • Universitaetsklinikum Schleswig-Holstein-Campus Luebeck ( Site 0803)

    Lübeck, 23538

  • Klinikum der Universitaet Munchen ( Site 0810)

    München, 81377

  • Universitaetsklinik Ulm ( Site 0804)

    Ulm, 89075

Other trials in Germany

Spain7 sites

  • H.U. Vall de Hebron ( Site 1052)

    Barcelona, 08035

  • Hospital Duran i Reynals ( Site 1053)

    L'Hospitalet de Llobregat, 08907

  • Hospital Doce de Octubre ( Site 1054)

    Madrid, 28024

  • Hospital Universitario Ramon y Cajal ( Site 1055)

    Madrid, 28034

  • Hospital Clinico San Carlos ( Site 1051)

    Madrid, 28040

  • Hospital Universitario Virgen de la Victoria ( Site 1056)

    Málaga, 29010

  • Hospital Gral Universitario de Valencia ( Site 1050)

    Valencia, 46014

Other trials in Spain

Taiwan7 sites

  • Chang Gung Medical Foundation - Kaohsiung ( Site 0501)

    Kaohsiung City, 83301

  • Taichung Veterans General Hospital ( Site 0506)

    Taichung, 407

  • National Cheng Kung University Hospital ( Site 0503)

    Tainan, 70403

  • National Taiwan University Hospital ( Site 0500)

    Taipei, 10048

  • MacKay Memorial Hospital ( Site 0505)

    Taipei, 105

  • Taipei Veterans General Hospital ( Site 0504)

    Taipei, 112

  • Linkou Chang Gung Memorial Hospital ( Site 0502)

    Taoyuan, 333

Other trials in Taiwan

Australia6 sites

  • Royal Adelaide Hospital ( Site 0303)

    Adelaide, South Australia, 5000

  • Blacktown Hospital Western Sydney Local Health District ( Site 0304)

    Blacktown, New South Wales, 2148

  • Princess Alexandra Hospital ( Site 0305)

    Brisbane, Queensland, 4102

  • Royal Brisbane and Women s Hospital ( Site 0302)

    Herston, Queensland, 4029

  • Liverpool Hospital ( Site 0301)

    Liverpool, New South Wales (Australia), 2170

  • Peter MacCallum Cancer Centre ( Site 0300)

    Melbourne, Victoria, 3000

Other trials in Australia

Czechia6 sites

  • FN Brno. ( Site 0703)

    Brno, 625 00

  • Fakultni Nemocnice Hradec Kralove ( Site 0705)

    Hradec Králové, 500 05

  • Fakultni nemocnice Olomouc ( Site 0701)

    Olomouc, 775 20

  • Fakultni nemocnice Ostrava ( Site 0702)

    Ostrava, 708 52

  • 2. LF UK a FN Motol ( Site 0704)

    Prague, 150 06

  • Nemocnice Na Bulovce ( Site 0700)

    Prague, 180 81

Other trials in Czechia

Belgium5 sites

  • Cliniques Universitaires Saint Luc - Bruxelles ( Site 0651)

    Brussels, 1200

  • UZ Gent ( Site 0650)

    Ghent, 9000

  • UZ Leuven Campus Gasthuisberg ( Site 0652)

    Leuven, 3000

  • C.H.U. Sart Tilman-Service d'Oncologie Medicale ( Site 0654)

    Liège, 4000

  • Clinique et Maternite Sainte-Elisabeth ( Site 0653)

    Namur, 5000

Other trials in Belgium

France5 sites

  • Centre Jean Bernard Laboratoire Mahe Meziani ( Site 0760)

    Le Mans, 72000

  • Clinique Francois Chenieux ( Site 0757)

    Limoges, 87039

  • Institut Claudius Regaud ( Site 0754)

    Toulouse, 31059

  • Institut De Cancerologie De Lorraine ( Site 0758)

    Vandœuvre-lès-Nancy, 54500

  • Institut Gustave Roussy ( Site 0759)

    Villejuif, 94805

Other trials in France

Israel5 sites

  • Rambam MC ( Site 0903)

    Haifa, 3109601

  • Hadassah Ein Karem Jerusalem ( Site 0902)

    Jerusalem, 9112001

  • Rabin Medical Center ( Site 0904)

    Petah Tikva, 4941492

  • Sheba MC ( Site 0901)

    Ramat Gan, 5265601

  • Tel Aviv Sourasky Medical Center ( Site 0900)

    Tel Aviv, 6423906

Other trials in Israel

Netherlands5 sites

  • Noordwest Ziekenhuisgroep NWZ ( Site 1350)

    Alkmaar, 1815 JD

  • VU Medisch Centrum ( Site 1352)

    Amsterdam, 1081 HV

  • UMCG ( Site 1351)

    Groningen, 9713 GZ

  • UMC St. Radboud ( Site 1356)

    Nijmegen, 6525 GA

  • Erasmus University Medical Center ( Site 1354)

    Rotterdam, 3015 GD

Other trials in Netherlands

South Korea5 sites

  • Chungbuk National University Hospital ( Site 0454)

    Cheongju-si, North Chungcheong, 28644

  • Chungnam National University Hospital ( Site 0455)

    Daejeon, 35015

  • Seoul National University Bundang Hospital ( Site 0453)

    Seongnam-si, Gyeonggi-do, 13620

  • Severance Hospital Yonsei University Health System ( Site 0452)

    Seoul, 03722

  • Samsung Medical Center ( Site 0450)

    Seoul, 06351

Other trials in South Korea

Austria4 sites

  • Landeskrankenhaus - Universitatsklinikum Graz ( Site 0601)

    Graz, 8036

  • Krankenhaus der Barmherzigen Schwestern Linz ( Site 0603)

    Linz, 4010

  • Landeskrankenhaus Salzburg ( Site 0600)

    Salzburg, 5020

  • Allgemeines Krankenhaus der Stadt Wien ( Site 0602)

    Vienna/Wien, 1090

Other trials in Austria

Colombia4 sites

  • Centro de Investigacion Clinica del Country ( Site 0155)

    Bogotá, 110221

  • Fundacion Valle del Lili ( Site 0150)

    Cali, Valle del Cauca Department, 760032

  • Centro Medico Imbanaco de Cali S.A ( Site 0156)

    Cali, Valle del Cauca Department, 760042

  • Hospital Pablo Tobon Uribe ( Site 0151)

    Medellín, Antioquia, 050034

Other trials in Colombia

New Zealand1 site

  • Capital & Coast District Health Board - Wellington Hospital ( Site 0400)

    Wellington, Newtown, 6021

Other trials in New Zealand

About this study

Official title: A Randomized Phase III Study of Pembrolizumab Given Concomitantly With Chemoradiation and as Maintenance Therapy Versus Chemoradiation Alone in Subjects With Locally Advanced Head and Neck Squamous Cell Carcinoma (KEYNOTE-412)

The purpose of this study is to determine the efficacy and safety of pembrolizumab given concomitantly with chemoradiation (CRT) and as maintenance therapy versus placebo plus CRT in participants with locally advanced head and neck squamous cell carcinoma (LA HNSCC). The primary hypothesis is that pembrolizumab in combination with CRT is superior to placebo in combination with CRT with respect to event-free survival (EFS).

Being tested
Pembrolizumab, Placebo, Cisplatin, Accelerated Fractionation (AFX) Radiotherapy, Standard Fractionation (SFX) Radiotherapy
Keywords
Head and Neck Squamous Cell Carcinoma, Programmed Cell Death Receptor 1 (PD-1), Programmed Cell Death Receptor Ligand 1 (PD-L1), Programmed Cell Death Receptor Ligand 2 (PD-L2), PD1, PD-1, PDL1, PD-L1, PDL2
Medical subject headings
Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called KEYTRUDA®

    Administered as an intravenous (IV) infusion every 3 weeks (Q3W)

  • PlaceboDrug

    Normal saline or dextrose solution administered as an IV infusion Q3W

  • CisplatinDrug

    Also called Platinol®, Platinol®-AQ

    100 mg/m^2 administered as an IV infusion Q3W

  • Accelerated Fractionation (AFX) RadiotherapyRadiation

    70 Gray (Gy) given in 35 fractions over 6 weeks

  • Standard Fractionation (SFX) RadiotherapyRadiation

    70 Gy given in 35 fractions over 7 weeks

Study groups in NCT03040999
Study groupRoleWhat they receive
Pembrolizumab + Cisplatin + CRTExperimentalParticipants receive a priming dose of pembrolizumab before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of pembrolizumab and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of pembrolizumab alone as maintenance therapy for a total of 17 cycles of pembrolizumab. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with pembrolizumab.
Receives: Biological: Pembrolizumab; Drug: Cisplatin; Radiation: Accelerated Fractionation (AFX) Radiotherapy; Radiation: Standard Fractionation (SFX) Radiotherapy
Placebo + Cisplatin + CRTPlacebo comparatorParticipants receive placebo before initiation of CRT (either accelerated or standard fractionation radiotherapy regimen). During CRT, participants receive 2 doses of placebo and up to 3 cycles of Cisplatin (2 cycles during accelerated and 3 cycles during standard fractionation radiotherapy). Participants also receive up to an additional 14 cycles of placebo alone for a total of 17 cycles of placebo. If cisplatin and/or radiation therapy is discontinued, the participant may continue on treatment with placebo.
Receives: Drug: Placebo; Drug: Cisplatin; Radiation: Accelerated Fractionation (AFX) Radiotherapy; Radiation: Standard Fractionation (SFX) Radiotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Event-free Survival (EFS)

    EFS was defined as the time from date of randomization to the date of first record of any of the following events: death due to any cause; progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) or biopsy as indicated for locoregional progression or recurrence or distant metastasis. As well as the first record of the following types of surgery: salvage surgery for persistent or residual disease at the primary tumor site requiring surgical removal when invasive cancer is present on final pathology; neck dissection or surgery (performed for clinical or radiological disease progression per RECIST 1.1) ≤ 20 weeks from end of CRT when invasive cancer is present; or neck dissection or surgery >20 weeks from end of CRT when invasive cancer is present. The non-parametric Kaplan-Meier method was used to estimate the EFS curve in each treatment group.

    Measured: Up to approximately 62 months

Secondary outcomes (8)

  1. Overall Survival (OS)

    OS was defined as the time from the date of randomization to the date of death due to any cause. Participants without documented death at the time of analysis were censored at the date the participant was last known to be alive. The non-parametric Kaplan-Meier method was used to estimate the survival curve in each treatment group.

    Measured: Up to approximately 62 months

  2. Number of Participants Who Experienced an Adverse Event (AE)

    An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who experienced an AE is presented.

    Measured: Up to approximately 88 months

  3. Number of Participants Who Discontinued Study Drug Due to an AE

    An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. An AE is any sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study therapy. The number of participants who discontinued study drug due to an AE is presented.

    Measured: Up to approximately 15 months

  4. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) Score

    The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. For Global Health Status (GHS) (Item 29), participants are asked "How would you rate your overall health during the past week?" Individual items are scored on a 7-point (1=very poor to 7=excellent). Raw scores for each scale are standardized into a range of 0 to 100 by linear transformation, with a higher score indicating a better level of function and better overall GHS. A change from baseline of 10 points on the 100-point EORTC QLQ-C30 scale is considered as clinically relevant. Analysis based on a constrained longitudinal data analysis (cLDA) model with the patient reported outcomes (PRO) scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of human papilloma virus (HPV) status and overall cancer stage.

    Measured: Baseline and up to week 45

  5. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Swallowing Score

    EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in swallowing was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

    Measured: Baseline and up to Week 45

  6. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Speech Score

    EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and neck cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the speech scale (Items 30-32) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in speech was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

    Measured: Baseline and up to Week 45

  7. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck Questionnaire (EORTC QLQ-H&N35) Pain Symptom Score

    EORTC QLQ Head and Neck Questionnaire (H\&N35) measures QoL in head and Neck Cancer (HNC) patients. It consists of 7 multi-item scales (pain in the mouth, problems with swallowing, senses, speech, social eating, social contact, and sexuality). Participant responses to the pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Change from baseline in pain symptoms was measured. A change from baseline of 10 points on the 100-point EORTC QLQ-H\&N35 is considered as clinically relevant. Analysis based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

    Measured: Baseline and up to Week 45

  8. Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning Score

    The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life (QoL) of cancer patients. Participant responded to 5 questions from the EORTC QLQ-C30 about their physical functioning scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100, where a higher score indicates a better physical functioning. A change from baseline of 10 points on the 100-point scale is considered as clinically relevant. Analysis was based on a cLDA model with the PRO scores as the response variable with covariates for treatment, time, treatment by time interaction, and stratification factors of HPV status and overall cancer stage.

    Measured: Baseline and up to Week 45

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2017 (estimated)
  2. Study start5 Apr 2017
  3. Primary completion31 May 2022
  4. Study completion21 Aug 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
804 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03040999
Sponsor's protocol ID
3475-412
Other IDs
MK-3475-412, 173640, KEYNOTE-412, 2016-003934-25, 2016
Status last verified
Dec 2025
First submitted
1 Feb 2017
Last updated
4 Feb 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • Machiels JP, Tao Y, Licitra L, Burtness B, Tahara M, Rischin D, Alves G, Lima IPF, Hughes BGM, Pointreau Y, Aksoy S, Laban S, Greil R, Burian M, Hetnal M, Delord JP, Mesia R, Taberna M, Waldron JN, Simon C, Gregoire V, Harrington KJ, Swaby RF, Zhang Y, Gumuscu B, Bidadi B, Siu LL; KEYNOTE-412 Investigators. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2024 May;25(5):572-587. doi: 10.1016/S1470-2045(24)00100-1. Epub 2024 Mar 29.

    PubMed 38561010

  • Machiels JP, Tao Y, Burtness B, Tahara M, Licitra L, Rischin D, Waldron J, Simon C, Gregoire V, Harrington K, Alves GV, Figueiredo Lima IP, Pointreau Y, M Hughes BG, Aksoy S, Hetnal M, Ge JY, Brown H, Cheng J, Bidadi B, Siu LL. Pembrolizumab given concomitantly with chemoradiation and as maintenance therapy for locally advanced head and neck squamous cell carcinoma: KEYNOTE-412. Future Oncol. 2020 Jun;16(18):1235-1243. doi: 10.2217/fon-2020-0184. Epub 2020 Jun 3.

    PubMed 32490686

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pembrolizumab, Cisplatin and Accelerated Fractionation (AFX) Radiotherapy in people with Head and Neck Neoplasms, run by Merck Sharp & Dohme LLC at 151 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 151 sites in United States, Japan, Brazil, United Kingdom, Canada and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jun 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free Survival (EFS) (time frame: Up to approximately 62 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03040999, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.

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