Esophageal Squamous Cell Carcinoma (ESCC)Phase 3NCT04210115
Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)
A Phase 3 study testing pembrolizumab, cisplatin and 5-FU in people with Esophageal Squamous Cell Carcinoma (ESCC) and Gastroesophageal Junction Carcinoma (GEJC), run by Merck Sharp & Dohme LLC at 170 sites in 27 countries.
Trial summary
The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in: participants whose tumors express Programmed Death-Ligand 1… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Esophageal Squamous Cell Carcinoma (ESCC), Gastroesophageal Junction Carcinoma (GEJC), Esophageal Adenocarcinoma (EAC)
- What is being tested?
- pembrolizumab, cisplatin and 5-FU
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 703 participants
- Where
- 170 sitesin 27 countries
- Study dates
- 28 Feb 2020to 23 Jun 2026
- Phase
- Phase 3
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 histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+ M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node metastases only
- Is deemed suitable for dCRT
- Is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist.
- Is not expected to require tumor resection during the course of the study
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment
- Has adequate organ function
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- Male participants must use adequate contraception (a male condom plus partner use of an additional contraceptive method) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) and refrain from donating sperm during the study treatment period and through 90 days after the last dose of chemotherapy
- Female participants who are a Woman of Childbearing Potential (WOCBP) must use contraception that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the study treatment period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agree not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
- Female participants must not be pregnant or breastfeeding
Who cannot join
- Has direct invasion of tumor into adjacent organs such as the aorta or trachea or has radiographic evidence of >90 degree encasement or invasion of a major blood vessel, or of intratumoral cavitation
- Has had major surgery other than for insertion of a feeding tube, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipates the need for major surgery during study treatment; participants with gastric or esophageal fistulae are excluded
- Has had weight loss of >20% in the previous 3 months
- Has had prior chemotherapy or radiotherapy for esophageal cancer
- Has had a myocardial infarction within the past 6 months
- Has symptomatic congestive heart failure
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- Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
- Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed
- Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents
- Has not recovered from all adverse events (AEs) due to previous non-anticancer therapies to ≤Grade 1 or Baseline
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded from the study. Participants with localized prostate cancer that has undergone potentially curative treatment can be enrolled in the study.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their excipients
- 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 Hepatitis B or known active Hepatitis C virus infection
- Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment (180 days for participants receiving cisplatin who are breastfeeding)
- Has had an allogeneic tissue/solid organ transplant
Trial locations and contacts
170 sites in 27 countries.
170 sites in 27 countries
United States19 sites
Greater Baltimore Medical Center ( Site 0031)
Baltimore, Maryland, 21204
Dana Farber Cancer Center ( Site 0034)
Boston, Massachusetts, 02215
University of Missouri ( Site 0688)
Columbia, Missouri, 65212
Columbus Regional Research Institute ( Site 0047)
Columbus, Georgia, 31904
Henry Ford Hospital ( Site 0685)
Detroit, Michigan, 48202
Thompson Cancer Survival Center ( Site 0696)
Knoxville, Tennessee, 37916
MemorialCare Health System - Long Beach Medical Center-Oncology ( Site 0691)
Long Beach, California, 90806
University of Wisconsin Hospital and Clinics ( Site 0033)
Madison, Wisconsin, 53792
Rutgers Cancer Institute of New Jersey ( Site 0695)
New Brunswick, New Jersey, 08903
University Medical Center ( Site 0035)
New Orleans, Louisiana, 70112
Weill Cornell Medical College ( Site 0053)
New York, New York, 10065
Stephenson Cancer Center ( Site 0044)
Oklahoma City, Oklahoma, 73104
Allegheny Health Network ( Site 0042)
Pittsburgh, Pennsylvania, 15212
Oregon Health & Science University Center for Health & Healing 2- CHH2 ( Site 0060)
Portland, Oregon, 97239
Renown Regional Medical Center ( Site 0706)
Reno, Nevada, 89502
Utah Cancer Specialists ( Site 0697)
Salt Lake City, Utah, 84106
Cancer Care Northwest - Spokane Valley ( Site 0036)
Spokane Valley, Washington, 99216
University of Kansas Cancer Center ( Site 0023)
Westwood, Kansas, 66205
Cancer Center of Kansas ( Site 0058)
Wichita, Kansas, 67214
China18 sites
Hunan Cancer Hospital ( Site 0515)
Changsha, Hunan, 410006
Sichuan Cancer Hospital ( Site 0527)
Chengdu, Sichuan, 610041
The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si
Fuzhou, Fujian, 350025
Hangzhou First People's Hospital ( Site 0530)
Hangzhou, Zhejiang, 310002
Sir Run Run Shaw Hospital ( Site 0523)
Hangzhou, Zhejiang, 310018
Zhejiang Cancer Hospital ( Site 0529)
Hangzhou, Zhejiang, 310022
Anhui Provincial Hospital-Oncology Radiotherapy Department ( Site 0531)
Hefei, Anhui, 230071
Huai an First People s Hospital ( Site 0526)
Huai'an, Jiangsu, 223001
Jiangxi Cancer Hospital ( Site 0512)
Nanchang, Jiangxi, 330029
Jiangsu Cancer Hospital ( Site 0519)
Nanjing, Jiangsu, 210000
Shanghai Chest Hospital ( Site 0501)
Shanghai, Shanghai Municipality, 200030
Shanghai Chest Hospital ( Site 0503)
Shanghai, Shanghai Municipality, 200030
Zhongshan Hospital Fudan University ( Site 0502)
Shanghai, Shanghai Municipality, 200032
Tianjin Medical University Cancer Institute & Hospital ( Site 0505)
Tianjin, Tianjin Municipality, 300060
Hubei Cancer Hospital ( Site 0514)
Wuhan, Hubei, 430079
The First Affiliated Hospital of Xiamen University ( Site 0538)
Xiamen, Fujian, 361003
The Affiliated Hospital of Xuzhou Medical University ( Site 0522)
Xuzhou, Jiangsu, 221002
Affiliated Hospital of Jiangsu University ( Site 0524)
Zhenjiang, Jiangsu, 212000
France10 sites
CHU Amiens Picardie Site Sud Amiens ( Site 0235)
Amiens, Somme, 80054
Institut Sainte Catherine ( Site 0228)
Avignon, Provence-Alpes-Côte d'Azur Region, 84918
Centre Francois Baclesse ( Site 0236)
Caen, Calvados, 14075
Centre Georges Francois Leclerc ( Site 0223)
Dijon, Cote-d Or, 21079
CHD Vendee ( Site 0227)
La Roche-sur-Yon, Vendee, 85925
CHU Limoges Hopital Dupuytren ( Site 0225)
Limoges, Haute-Vienne, 87042
CHU Hotel Dieu Nantes ( Site 0230)
Nantes, Pays de la Loire Region, 44093
Institut Jean Godinot ( Site 0238)
Reims, Marne, 51726 CEDEX
Institut Curie - Centre Rene Huguenin ( Site 0237)
Saint-Cloud, Hauts-de-Seine, 92210
Institut De Cancerologie De Lorraine ( Site 0222)
Vandœuvre-lès-Nancy, Ain, 54519
United Kingdom10 sites
Aberdeen Royal Infirmary ( Site 0474)
Aberdeen, Aberdeen City, AB25 2ZN
Cambridge University Hospitals NHS Trust ( Site 0477)
Cambridge, Cambridgeshire, CB2 0QQ
Royal Free Hospital ( Site 0702)
London, England, NW32QG
ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0283)
London, London, City of, SW3 6JJ
Hammersmith Hospital-Medical Oncology ( Site 0471)
London, London, City of, W12 OHS
University College Hospital NHS Foundation Trust ( Site 0701)
London, Worcestershire, NW1 2PG
The Christie NHS Foundation Trust ( Site 0282)
Manchester, M20 4BX
Mount Vernon Hospital ( Site 0478)
Northwood, HA6 2RN
Nottingham University Hospitals NHS Trust ( Site 0476)
Nottingham, Nottinghamshire, NG5 1PB
Royal Marsden Hospital (Sutton) ( Site 0281)
Sutton, Surrey, SM2 5PT
Italy9 sites
ASST Papa Giovanni XXIII ( Site 0296)
Bergamo, 24127
Azienda Socio Sanitaria Territoriale di Cremona ( Site 0299)
Cremona, 26100
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0292)
Milan, 20133
Istituto Nazionale Tumori IRCCS Fondazione Pascale-SC Oncologia Clinica Sperimentale Addome ( Site 0
Naples, 80131
IRCCS Istituto Oncologico Veneto ( Site 0298)
Padova, 35128
Fondazione IRCCS Policlinico San Matteo-Oncology ( Site 0300)
Pavia, Lombardy, 27100
Azienda Ospedaliero Universitaria Pisana - Presidio Santa Chiara ( Site 0294)
Pisa, Tuscany, 56126
Policlinico Universitario A. Gemelli ( Site 0297)
Roma, 00168
IRCCS Policlinico San Donato ( Site 0295)
San Donato Milanese, Milano, 20097
Russia9 sites
Kaluga Regional Clinical Oncology Center ( Site 0424)
Kaluga, Kaluzskaja Oblast, 248007
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0412)
Kazan', Tatarstan, Respublika, 420029
Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0421)
Moscow, Moscow, 105229
FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0429)
Moscow, Moscow, 125367
Pavlov First Saint Petersburg State Medical University ( Site 0426)
Saint Petersburg, Sankt-Peterburg, 197022
Medical institute named after Berezin Sergey ( Site 0417)
Saint Petersburg, Sankt-Peterburg, 197758
SBHI Samara Regional Clinical Oncology Dispensary ( Site 0420)
Samara, Samara Oblast, 443031
GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0430)
Ufa, Baskortostan, Respublika, 450054
Sverdlovsk Regional Oncology Hospital ( Site 0411)
Yekaterinburg, Sverdlovsk Oblast, 620036
Romania7 sites
MedEuropa Bucuresti - Centru de Radioterapie-Oncology ( Site 0400)
Bucharest, Bucharest, 022343
S.C.Focus Lab Plus S.R.L ( Site 0395)
Bucharest, 022548
Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0392)
Cluj-Napoca, Cluj, 400015
S.C. Radiotherapy Center Cluj S.R.L ( Site 0391)
Cluj-Napoca, Cluj, 407280
S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0394)
Craiova, Dolj, 200542
Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 0393)
Ovidiu, Constanța County, 905900
Centrul Medical Topmed ( Site 0398)
Târgu Mureş, Mureș County, 540156
Taiwan7 sites
Chang Gung Med Foundation. Kaohsiung Branch ( Site 0643)
Kaohsiung City, 833
China Medical University Hospital ( Site 0646)
Taichung, 40447
Taichung Veterans General Hospital-Radiation Oncology ( Site 0647)
Taichung, 407
National Cheng Kung University Hospital ( Site 0645)
Tainan, 70457
National Taiwan University Hospital ( Site 0641)
Taipei, 10002
Koo Foundation Sun Yat-Sen Cancer Center ( Site 0644)
Taipei, 11259
Chang Gung Medical Foundation. Linkou ( Site 0642)
Taoyuan, 33305
Canada6 sites
Cross Cancer Institute ( Site 0010)
Edmonton, Alberta, T6G 1Z2
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0005)
Montreal, Quebec, H2X 0A9
The Ottawa Hospital - Cancer Care ( Site 0008)
Ottawa, Ontario, K1H 8L6
Sunnybrook Research Institute ( Site 0012)
Toronto, Ontario, M4N 3M5
Princess Margaret Cancer Centre ( Site 0011)
Toronto, Ontario, M5G 2M9
CancerCare Manitoba ( Site 0002)
Winnipeg, Manitoba, R3E 0V9
Germany6 sites
Charite Campus Virchow Klinikum ( Site 0250)
Berlin, 13353
Universitaetsklinikum Koeln ( Site 0251)
Cologne, North Rhine-Westphalia, 50937
Facharztzentrum Eppendorf ( Site 0242)
Hamburg, 20249
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 0247)
Mainz, Rhineland-Palatinate, 55131
Universitaetsklinikum Muenster ( Site 0248)
Münster, North Rhine-Westphalia, 48149
Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0253)
Stuttgart, Baden-Wurttemberg, 70199
Guatemala6 sites
Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0122)
Guatemala City, 01010
Gastrosoluciones ( Site 0126)
Guatemala City, 01010
Oncomedica ( Site 0125)
Guatemala City, 01010
Grupo Medico Angeles ( Site 0121)
Guatemala City, 01015
Medi-K Cayala ( Site 0124)
Guatemala City, 01016
Centro Medico Integral De Cancerología (CEMIC) ( Site 0123)
Quetzaltenango, 09002
Japan6 sites
National Cancer Center Hospital East ( Site 0562)
Kashiwa, Chiba, 2778577
Saitama Cancer Center ( Site 0564)
Kitaadachi-gun, Saitama, 362-0806
Aichi Cancer Center Hospital ( Site 0563)
Nagoya, Aichi-ken, 464-8681
Shizuoka Cancer Center Hospital and Research Institute ( Site 0566)
Sunto-gun, Shizuoka, 411-8777
National Cancer Center Hospital ( Site 0561)
Tokyo, 104-0045
Kanagawa Cancer Center ( Site 0565)
Yokohama, Kanagawa, 241-8515
South Korea6 sites
National Cancer Center ( Site 0626)
Goyang-si, Kyonggi-do, 10408
Chonnam National University Hwasun Hospital ( Site 0625)
Hwasun Gun, Jeonranamdo, 58128
Severance Hospital Yonsei University Health System ( Site 0624)
Seoul, 03722
Samsung Medical Center ( Site 0622)
Seoul, 06351
Korea University Guro Hospital ( Site 0621)
Seoul, 08308
Asan Medical Center ( Site 0623)
Songpagu, Seoul, 05505
Portugal5 sites
Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0372)
Lisbon, 1099-023
Hospital da Luz ( Site 0373)
Lisbon, 1500 650
CHLN Hospital Santa Maria ( Site 0376)
Lisbon, 1649-035
Hospital Beatriz Angelo ( Site 0374)
Loures, Lisbon District, 2674-514
Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0371)
Porto, 4200-072
Turkey (Türkiye)5 sites
Memorial Ankara Hastanesi ( Site 0461)
Ankara, 06520
Istanbul University Cerrahpasa Medical Faculty ( Site 0452)
Istanbul, Istanbul, 34098
Göztepe Prof. Dr. Süleyman Yalçın Şehir Hastanesi-oncology ( Site 0451)
Istanbul, 34722
Ege Universitesi Tip Fakultesi ( Site 0457)
Izmir, 35040
Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 0458)
Izmir, 35360
Argentina4 sites
Instituto Medico Alexander Fleming ( Site 0063)
Buenos Aires, Buenos Aires F.D., C1426ANZ
Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0066)
Buenos Aires, C1264AAA
CEMIC ( Site 0064)
Buenos Aires, C1431FWO
Fundacion Favaloro ( Site 0061)
Ciudad de Buenos Aires, Buenos Aires F.D., C1093AAS
Belgium4 sites
UCL Saint Luc ( Site 0162)
Brussels, Bruxelles-Capitale, Region de, 1200
UZ Gent ( Site 0163)
Ghent, Oost-Vlaanderen, 9000
UZ Leuven ( Site 0161)
Leuven, Vlaams-Brabant, 3000
AZ Delta ( Site 0165)
Roeselare, West-Vlaanderen, 8800
Brazil4 sites
Clinica de Oncologia Reichow ( Site 0085)
Blumenau, Santa Catarina, 89010-340
ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0088)
Ijuí, Rio Grande do Sul, 98700-000
Hospital Nossa Senhora da Conceicao ( Site 0087)
Porto Alegre, Rio Grande do Sul, 91350-200
Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0081)
São Paulo, 01246-000
Chile4 sites
Hospital Regional de Concepcion ( Site 0105)
Concepción, Biobio, 4070038
Centro de Cancer Nuestra Senora de la Esperanza ( Site 0104)
Santiago, Region M. de Santiago, 8330024
Centro Investigación del Cáncer James Lind ( Site 0106)
Temuco, Araucania, 4800827
Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0103)
Temuco, Araucania, 4810218
Czechia4 sites
Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0721)
Brno, Brno-mesto, 656 53
Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 0720)
Olomouc, Olomouc Region, 779 00
Fakultni nemocnice Ostrava-Klinika onkologicka ( Site 0719)
Ostrava, Moravian-Silesian Region, 708 52
Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0718)
Prague, Praha 5, 150 06
Hungary4 sites
Orszagos Onkologiai Intezet ( Site 0263)
Budapest, 1122
Debreceni Egyetem Klinikai Kozpont ( Site 0261)
Debrecen, 4032
Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0262)
Gyula, Bekes County, 5700
Pecsi Tudomanyegyetem AOK ( Site 0265)
Pécs, Baranya, 7624
Peru4 sites
Instituto Nacional de Enfermedades Neoplasicas ( Site 0141)
Lima, Muni Metro de Lima, Lima 34
Hospital Nacional Arzobispo Loayza ( Site 0143)
Lima, 15082
Clinica San Gabriel ( Site 0142)
Lima, 15087
Detecta Clínica ( Site 0146)
Surquillo, Muni Metro de Lima, 15038
Philippines4 sites
Baguio General Hospital and Medical Center ( Site 0603)
Baguio City, Benguet, 2600
Cebu Doctors University Hospital ( Site 0604)
Cebu City, Cebu, 6000
The Medical City-Iloilo ( Site 0602)
Iloilo City, Iloilo, 5000
St. Luke s Medical Center ( Site 0601)
Quezon City, National Capital Region, 1102
Hong Kong3 sites
Pamela Youde Nethersole Eastern Hospital ( Site 0543)
Hong Kong
Princess Margaret Hospital. ( Site 0542)
Hong Kong
Queen Mary Hospital ( Site 0541)
Pokfulam
Denmark2 sites
Rigshospitalet ( Site 0199)
Copenhagen, Capital Region, 2100
Odense Universitetshospital ( Site 0200)
Odense, Region Syddanmark, 5000
Estonia2 sites
SA Pohja-Eesti Regionaalhaigla ( Site 0201)
Tallinn, Harju, 13419
SA Tartu Ulikooli Kliinikum ( Site 0202)
Tartu, Tartu, 50406
Mexico2 sites
Cryptex Investigación Clínica S.A. de C.V. ( Site 0729)
Cuauhtémoc, Ciudad de México, Mexico City, 06100
CENTRO HEMATO ONCOLOGICO PRIVADO-CHOP ( Site 0728)
Toluca, 50120
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)
The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:
- participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10
- participants whose tumors express PD-L1 CPS ≥1
- all participants
Read more
The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:
- EFS in participants whose tumors express PD-L1 CPS ≥10
- EFS in participants whose tumors express PD-L1 CPS ≥1
- EFS in all participants
- OS in participants whose tumors express PD-L1 CPS ≥10
- OS in participants whose tumors express PD-L1 CPS ≥1
- OS in all participants
Read the detailed description
Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:
- FP (5-fluorouracil [5-FU] + cisplatin) or
- FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).
- Conditions
- Esophageal Squamous Cell Carcinoma (ESCC), Gastroesophageal Junction Carcinoma (GEJC), Esophageal Adenocarcinoma (EAC)
- Being tested
- pembrolizumab, placebo, cisplatin, 5-FU, radiotherapy
- Keywords
- Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Death-Ligand 2 (PDL2, PD-L2)
- Medical subject headings
- Esophageal Squamous Cell Carcinoma, Adenocarcinoma Of Esophagus, 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 MK-3475, KEYTRUDA®
IV infusion
placeboDrug
Also called Normal saline solution
IV infusion
cisplatinDrug
Also called PLATINOL®
IV infusion
5-FUDrug
Also called ADRUCIL®
IV infusion
radiotherapyRadiation
external radiation
leucovorinDrug
Also called calcium folinate, folinic acid
IV infusion
levoleucovorinDrug
Also called FUSILEV®, calcium levofolinate, levofolinic acid
IV infusion
oxaliplatinDrug
Also called ELOXATIN®
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab+FP or FOLFOX Therapy+Radiotherapy | Experimental | Participants receive pembrolizumab 200 mg on Day 1 of each 3-week cycle for 8 cycles followed by pembrolizumab 400 mg on Day 1 of each 6-week cycle for 5 cycles PLUS either:
* FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-fluorouracil (5-FU)] 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gray [Gy] in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR
* FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle.
All treatments except radiotherapy are given by intravenous (IV) infusion. Total treatment duration is approximately 1 year. Receives: Biological: pembrolizumab; Drug: cisplatin; Drug: 5-FU; Radiation: radiotherapy; Drug: leucovorin; Drug: levoleucovorin; Drug: oxaliplatin |
| Placebo+FP or FOLFOX Therapy+Radiotherapy | Placebo comparator | Participants receive placebo on Day 1 of each 3-week cycle for 8 cycles followed by placebo on Day 1 of each 6-week cycle for 5 cycles PLUS either:
* FP therapy: cisplatin 75 mg/m^2 on Day 1 of Weeks 1, 5, 8 and 11 PLUS 5-FU 1000 mg/m^2 per day on Days 1-4 of Weeks 1, 5, 8 and 11 OR 800 mg/m^2/day on each of Days 1-5 at Weeks 1, 5, 8, and 11 PLUS radiotherapy (either 50 Gy in 25 fractions OR 60 Gy in 30 fractions) on Days 1-5 of each 3-week cycle OR
* FOLFOX therapy: oxaliplatin 85 mg/m^2 AND either leucovorin 400 mg/m^2 OR levoleucovorin 200 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 PLUS either 5-FU 400 mg/m^2 on Day 1 of Weeks 1, 3, 5, 7, 9 and 11 OR 5-FU 800 mg/m^2 per day on Days 1 and 2 of Weeks 1, 3, 5, 7, 9 and 11 PLUS radiotherapy (50 Gy in 25 fractions) on Days 1-5 of each 3-week cycle.
All treatments except radiotherapy are given by IV infusion. Total treatment duration is approximately 1 year. Receives: Drug: placebo; Drug: cisplatin; Drug: 5-FU; Radiation: radiotherapy; Drug: leucovorin; Drug: levoleucovorin; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival (EFS)
EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occurs first.
Measured: Up to ~60 months
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Measured: Up to ~72 months
Secondary outcomes (2)
Number of participants with an adverse event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measured: Up to ~15 months
Number of participants discontinuing study treatment due to an adverse event (AE)
An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Measured: Up to ~12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2019
- Study start28 Feb 2020
- Primary completion21 Jan 2026
- Study completion23 Jun 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Esophageal Squamous Cell Carcinoma (ESCC)Studies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 703 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04210115
- Sponsor's protocol ID
- 3475-975
- Other IDs
- MK-3475-975, KEYNOTE-975, PHRR200210-002490, 205261, 2022-501531-16-00, U1111-1281-0822, 2019-002006-51, 2019
- Status last verified
- Jul 2026
- First submitted
- 20 Dec 2019
- Last updated
- 22 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Shah MA, Bennouna J, Doi T, Shen L, Kato K, Adenis A, Mamon HJ, Moehler M, Fu X, Cho BC, Bordia S, Bhagia P, Shih CS, Desai A, Enzinger P. KEYNOTE-975 study design: a Phase III study of definitive chemoradiotherapy plus pembrolizumab in patients with esophageal carcinoma. Future Oncol. 2021 Apr;17(10):1143-1153. doi: 10.2217/fon-2020-0969. Epub 2021 Feb 3.
PubMed 33533655