First-line Esophageal Carcinoma Study With Chemo vs. Chemo Plus Pembrolizumab (MK-3475-590/KEYNOTE-590)

A Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Pembrolizumab (MK-3475) in Combination With Cisplatin and 5-Fluorouracil Versus Placebo in Combination With Cisplatin and 5-Fluorouracil as First-Line Treatment in Subjects With Advanced/Metastatic Esophageal Carcinoma (KEYNOTE-590)

The purpose of this trial is to evaluate efficacy and safety of pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin and 5-fluorouracil (5-FU) versus placebo plus SOC chemotherapy with cisplatin and 5-FU as first-line treatment in participants with locally advanced or metastatic esophageal carcinoma.

The overall primary efficacy hypotheses are as follows:

1. In participants with esophageal squamous cell carcinoma (ESCC), participants whose tumors are programmed cell death-ligand 1 (PD-L1)-positive (defined as combined positive score [CPS] ≥10), ESCC participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, overall survival (OS) is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.
2. In participants with ESCC, participants whose tumors are PD-L1 positive (CPS ≥10), and in all participants, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator is superior with pembrolizumab plus SOC chemotherapy compared with placebo plus SOC chemotherapy.

Study Overview

• Status: Completed
• Conditions: Esophageal Neoplasms
• Intervention / Treatment: Biological: Pembrolizumab; Drug: Cisplatin; Drug: Placebo; Drug: 5-FU

• Study Type: Interventional
• Enrollment (Actual): 749
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman ( Site 0605)
  • Buenos Aires, Argentina, C1264AAA
    • Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0602)
  • Cordoba, Argentina, X5000JHQ
    • Sanatorio Allende - Cordoba ( Site 0604)
  • Cordoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico Cordoba ( Site 0601)
  • Rio Negro
    • Viedma, Rio Negro, Argentina, R8500ACE
      • Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0603)
• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital ( Site 2000)
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital. ( Site 2001)
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital ( Site 2005)
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health ( Site 2002)
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre ( Site 2003)
• Brazil
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clinicas de Porto Alegre ( Site 0200)
  • Sao Paulo, Brazil, 01246-000
    • Instituto do Cancer de Sao Paulo - ICESP ( Site 0206)
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30110-022
      • CETUS Hospital Dia Oncologia ( Site 0208)
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-550
      • Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0210)
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20231-050
      • Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0209)
  • RS
    • Passo Fundo, RS, Brazil, 99010-080
      • Hospital Sao Vicente de Paulo ( Site 0204)
    • Porto Alegre, RS, Brazil, 90610-000
      • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0201)
  • Rio Grande Do Sul
    • Santa Maria, Rio Grande Do Sul, Brazil, 97015-513
      • Clinica de Hematologia e Oncologia Viver Ltda ( Site 0211)
  • SP
    • Sao Paulo, SP, Brazil, 01323-903
      • Hospital Alemao Oswaldo Cruz ( Site 0207)
  • Sao Paulo
    • Sao Jose do Rio Preto, Sao Paulo, Brazil, 15090-000
      • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto. ( Site 0203)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre ( Site 0503)
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute ( Site 0502)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba ( Site 0500)
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Center ( Site 0508)
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - Cancer Care ( Site 0501)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0505)
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie-Centre ( Site 0504)
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0507)
• Chile
  • Concepcion, Chile, 4070038
    • Hospital Regional de Concepcion Dr. Guillermo Grant Benavente ( Site 1003)
  • Santiago, Chile, 7620002
    • Pontificia Universidad Catolica de Chile ( Site 1001)
  • Santiago, Chile, 8380456
    • Hospital Clinico Universidad de Chile ( Site 1002)
  • Temuco, Chile, 4810297
    • Clinica Alemana de Temuco ( Site 1006)
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital ( Site 0100)
  • Fuzhou, China, 350014
    • Fujian Provincial Cancer Hospital ( Site 0104)
  • Shanghai, China, 200030
    • Shanghai Chest Hospital ( Site 0111)
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center ( Site 0108)
  • Shanghai, China, 200127
    • Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital ( Site 0107)
  • Anhui
    • Hefei, Anhui, China, 230036
      • Anhui Provincial Hospital ( Site 0106)
    • Hefei, Anhui, China, 230088
      • The First Affiliated Hospital of Anhui Medical University ( Site 0112)
  • Beijing
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital ( Site 0123)
  • Fujian
    • Xiamen, Fujian, China, 361000
      • The First Affiliated Hospital of Xiamen University ( Site 0119)
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Guangdong General Hospital ( Site 0103)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Medical College Huazhong University of Science and Technology ( Site 0109)
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 0105)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University ( Site 0125)
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital ( Site 0101)
  • Shannxi
    • Xi'an, Shannxi, China, 710061
      • The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital ( Site 0116)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia, 050030
      • Rodrigo Botero SAS ( Site 2703)
  • Cordoba
    • Monteria, Cordoba, Colombia, 230018
      • Oncomedica S.A. ( Site 2701)
• Costa Rica
  • San Jose, Costa Rica, 10103
    • CIMCA Centro de Investigacion y Manejo del Cancer ( Site 2600)
  • San Jose, Costa Rica, 10103
    • Policlinico San Bosco ( Site 2602)
  • San Jose, Costa Rica, 10108
    • ICIMED - Instituto de Investigacion en Ciencias Medicas ( Site 2601)
• Denmark
  • Copenhagen, Denmark, 2100
    • Rigshospitalet ( Site 2301)
  • Odense, Denmark, 5000
    • Odense Universitetshospital ( Site 2300)
• France
  • Brest, France, 29200
    • CHU Brest - Institut de Cancerologie et d Hematologie ( Site 0305)
  • Caen, France, 14076
    • Centre Francois Baclesse ( Site 0310)
  • Lille, France, 59020
    • Centre Oscar Lambret ( Site 0304)
  • Montpellier, France, 34298
    • Institut du Cancer de Montpellier ( Site 0306)
  • Nantes Cedex 1, France, 44093
    • CHU de Nantes - Hotel Dieu ( Site 0303)
  • Paris, France, 75014
    • Institut Mutualiste Montsouris ( Site 0300)
  • Saint Etienne, France, 42055
    • CHU de Saint Etienne Hopital Nord ( Site 0309)
  • Cedex 8
    • Lyon, Cedex 8, France, 69373
      • Centre Leon Berard ( Site 0307)
• Germany
  • Dresden, Germany, 01067
    • Staedtisches Klinikum Dresden ( Site 1507)
  • Hamburg, Germany, 20249
    • Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 1502)
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig ( Site 1501)
  • Ludwigsburg, Germany, 71640
    • Klinikum Ludwigsburg ( Site 1509)
  • Mannheim, Germany, 68167
    • Universitatsklinikum Mannheim GmbH ( Site 1504)
  • Moenchengladbach, Germany, 41063
    • Klinik fuer Haematologie. Onkologie und Gastroenterologie ( Site 1508)
  • Munchen, Germany, 81675
    • III. Medizinische Klinik Klinikum rechts der Isar ( Site 1506)
• Guatemala
  • Guatemala, Guatemala, 01010
    • Centro de Investigacion Oncologica ( Site 1402)
  • Guatemala, Guatemala, 01010
    • Oncomedica ( Site 1400)
  • Guatemala, Guatemala, 01015
    • Grupo Medico Angeles ( Site 1401)
  • Guatemala, Guatemala, 01016
    • Medi-K Cayala ( Site 1404)
  • Quetzaltenango, Guatemala, 09001
    • Centro Regional de Sub Especialidades Medicas SA ( Site 1403)
• Hong Kong
  • Hong Kong, Hong Kong
    • Humanity Health Research Centre ( Site 1603)
  • Hong Kong, Hong Kong
    • Pamela Youde Nethersole Eastern Hospital ( Site 1601)
  • Hong Kong, Hong Kong
    • Princess Margaret Hospital. ( Site 1602)
  • Hong Kong, Hong Kong
    • Queen Mary Hospital ( Site 1600)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 0909)
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center ( Site 0900)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 0906)
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital ( Site 0922)
  • Gifu, Japan, 501-1194
    • Gifu University Hospital ( Site 0920)
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital ( Site 0919)
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital ( Site 0924)
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute ( Site 0923)
  • Osaka, Japan, 558-8558
    • Osaka General Medical Center ( Site 0912)
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital ( Site 0907)
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR ( Site 0904)
  • Tokyo, Japan, 160-8582
    • Keio University Hospital ( Site 0927)
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital ( Site 0902)
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East ( Site 0908)
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center ( Site 0901)
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital ( Site 0916)
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Hyogo Cancer Center ( Site 0913)
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital ( Site 0929)
  • Ibaraki
    • Kasama, Ibaraki, Japan, 309-1793
      • Ibaraki Prefectural Central Hospital ( Site 0918)
    • Tsukuba, Ibaraki, Japan, 305-8576
      • University of Tsukuba Hospital ( Site 0910)
  • Kagawa
    • Kita-gun, Kagawa, Japan, 761-0793
      • Kagawa University Hospital ( Site 0915)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St. Marianna University School of Medicine Hospital ( Site 0903)
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center ( Site 0921)
  • Oita
    • Yufu, Oita, Japan, 879-5593
      • Oita University Hospital ( Site 0930)
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital ( Site 0931)
    • Osakasayama, Osaka, Japan, 589-8511
      • Kindai University Hospital ( Site 0917)
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 0911)
    • Takatsuki, Osaka, Japan, 569-8686
      • Osaka Medical College Hospital ( Site 0925)
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center ( Site 0926)
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center Hospital and Research Institute ( Site 0914)
  • Tokyo
    • Mitaka, Tokyo, Japan, 181-8611
      • Kyorin University Hospital ( Site 0905)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Cancer Hospital ( Site 1301)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 1302)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 1303)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 1300)
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
      • National Cancer Center ( Site 1304)
  • Jeollanam Do
    • Hwasun Gun, Jeollanam Do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital ( Site 1305)
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur ( Site 1805)
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre ( Site 1802)
  • Selangor
    • Petaling Jaya, Selangor, Malaysia, 46050
      • Beacon International Specialist Centre ( Site 1803)
• Peru
  • Arequipa, Peru, 04000
    • Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 1702)
  • Lima, Peru, 15033
    • Hospital Nacional Guillermo Almenara Irigoyen ( Site 1701)
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplasicas ( Site 1705)
• Romania
  • Bucuresti, Romania, 031422
    • S.C.Gral Medical S.R.L ( Site 2406)
  • Constanta, Romania, 900591
    • Spitalul Clinic Judetean De Urgenta Constanta ( Site 2402)
  • Bihor
    • Oradea, Bihor, Romania, 410469
      • S C Pelican Impex SRL ( Site 2403)
  • Cluj
    • Comuna Floresti, Cluj, Romania, 407280
      • S.C. Radiotherapy Center Cluj S.R.L ( Site 2407)
  • Dolj
    • Craiova, Dolj, Romania, 200347
      • S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2404)
  • Sector 2
    • Bucuresti, Sector 2, Romania, 021389
      • S.C.Focus Lab Plus S.R.L ( Site 2401)
  • Timis
    • Timisoara, Timis, Romania, 300166
      • S C Oncocenter Oncologie Medicala S R L ( Site 2405)
• Russian Federation
  • Moscow, Russian Federation, 105203
    • National Medical and Surgical Center n.a. N.I.Pirogov ( Site 0402)
  • Moscow, Russian Federation, 115478
    • N.N. Blokhin NMRCO ( Site 0401)
  • Saint-Petersburg, Russian Federation, 197758
    • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0406)
  • St. Petersburg, Russian Federation, 198255
    • St Petersburg City Clinical Oncology Dispensary ( Site 0409)
  • Tomsk, Russian Federation, 634028
    • Tomsk Scientific Research Institute of Oncology ( Site 0403)
  • Republic Of Bashkortostan
    • Ufa, Republic Of Bashkortostan, Russian Federation, 450054
      • SBHCI RCOD of MHC RB ( Site 0407)
  • Vsevolzhsk District
    • Saint-Petersburg, Vsevolzhsk District, Russian Federation, 188663
      • Leningrad Regional Oncology Center ( Site 0405)
• South Africa
  • Alberton, South Africa, 1448
    • Clinton Oncology Centre ( Site 2505)
  • Eastern Cape
    • Port Elizabeth, Eastern Cape, South Africa, 6045
      • Cancer Care Langenhoven Drive Oncology Centre ( Site 2501)
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2196
      • The Medical Oncology Centre of Rosebank ( Site 2506)
    • Parktown, Gauteng, South Africa, 2193
      • WITS Clinical Research CMJAH Clinical Trial Site ( Site 2500)
  • Kwa-Zulu Natal
    • Durban, Kwa-Zulu Natal, South Africa, 4091
      • The Oncology Centre ( Site 2502)
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7570
      • Cape Town Oncology Trials Pty Ltd ( Site 2508)
    • George, Western Cape, South Africa, 6530
      • Outeniqua Cancercare Oncology Unit ( Site 2504)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 0702)
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina Sofia ( Site 0706)
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal ( Site 0703)
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz ( Site 0700)
  • Malaga, Spain, 29010
    • Complejo Hospitalario Virgen De La Victoria ( Site 0705)
  • Asturias
    • Oviedo, Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias ( Site 0708)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0701)
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Chang Gung Med Foundation. Kaohsiung Branch ( Site 1906)
  • New Taipei, Taiwan, 235
    • Taipei Medical University Shuang Ho Hospital ( Site 1908)
  • Taichung, Taiwan, 404
    • China Medical University Hospital ( Site 1904)
  • Taichung, Taiwan, 43303
    • Kuang Tien General Hospital ( Site 1909)
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital ( Site 1905)
  • Tainan, Taiwan, 736
    • Chi Mei Medical Center Liuying ( Site 1907)
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital ( Site 1900)
  • Taipei, Taiwan, 11259
    • Koo Foundation Sun Yat-Sen Cancer Center ( Site 1902)
  • Taoyuan, Taiwan, 333
    • Chang Gung Medical Foundation. Linkou ( Site 1903)
• Thailand
  • Bangkok, Thailand, 10110
    • Bumrungrad International Hospital ( Site 2203)
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital ( Site 2201)
  • Bangkok, Thailand, 10330
    • Ramathibodi Hospital. ( Site 2202)
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital ( Site 2205)
  • Songkla, Thailand, 90110
    • Songklanagarind Hospital ( Site 2204)
• Turkey
  • Adana, Turkey, 01370
    • Adana Sehir Hastanesi ( Site 0802)
  • Ankara, Turkey, 06800
    • Ankara Sehir Hastanesi ( Site 0808)
  • Istanbul, Turkey, 34093
    • Istanbul Medeniyet Universitesi Goztepe EAH ( Site 0807)
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0804)
  • Istanbul, Turkey, 34899
    • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0801)
  • Izmir, Turkey, 35575
    • Medical Park Izmir Hastanesi ( Site 0800)
  • Malatya, Turkey, 44280
    • Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 0803)
• United Kingdom
  • Guildford, United Kingdom, GU2 7XX
    • St Luke's Cancer Centre ( Site 1102)
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust ( Site 1100)
  • Mid Lothian
    • Edinburgh, Mid Lothian, United Kingdom, EH4 2XU
      • Lothian University Hospitals NHS Trust ( Site 1101)
• United States
  • California
    • West Los Angeles, California, United States, 90034
      • Kaiser Permanente Southern California ( Site 0003)
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center ( Site 0001)
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas ( Site 0029)
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center ( Site 0013)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Center ( Site 0009)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Center ( Site 0018)
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine ( Site 0031)
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute ( Site 0004)
    • New York, New York, United States, 10065
      • Weill Cornell Medical College ( Site 0024)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center ( Site 0002)
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center/Hillman Cancer Center ( Site 0015)
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center Knoxville ( Site 0017)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the esophagogastric junction (EGJ)
• Has measurable disease per RECIST 1.1 as determined by the local site investigator/radiology assessment
• Eastern Cooperative Group (ECOG) performance status of 0 to 1
• Can provide either a newly obtained or archival tissue sample for PD-L1 by immunohistochemistry analysis
• Female participants of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to randomization and be willing to use an adequate method of contraception (e.g. abstinence, intrauterine device, diaphragm with spermicide, etc.) for the course of the study through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin
• Male participants of childbearing potential must agree to use an adequate method of contraception (e.g. abstinence, vasectomy, male condom, etc.) starting with the first dose of study treatment through 120 days after the last dose of study treatment and up to 180 days after last dose of cisplatin, and refrain from donating sperm during this period
• Has adequate organ function

Exclusion Criteria:

• Has locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy (as determined by local investigator)
• Has had previous therapy for advanced/metastatic adenocarcinoma or squamous cell cancer of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the EGJ
• Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ breast cancer that has undergone potentially curative therapy, and in situ or intramucosal pharyngeal cancer
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment, or has a history of organ transplant, including allogeneic stem cell transplant
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis, or has an active infection requiring systemic therapy
• 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 medication and up to 180 days after last dose of cisplatin
• Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor or has previously participated in a pembrolizumab (MK-3475) clinical trial
• Has severe hypersensitivity (≥ Grade 3) to any study treatment (pembrolizumab, cisplatin, or 5-FU) and/or any of its excipients
• Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis) or human immunodeficiency virus (HIV) infection
• Has known history of or is positive for hepatitis B or hepatitis C
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has had radiotherapy within 14 days of randomization. Participants who received radiotherapy >14 days prior to randomization must have completely recovered from any radiotherapy-related AEs/toxicities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + SOC; Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) plus standard of care (SOC) chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.	Biological: Pembrolizumab; 200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.; Other Names: MK-3475; Drug: Cisplatin; 80 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.; Drug: 5-FU; 800 mg/m^2/day (4000 mg/m^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration, up to 35 administrations.
Placebo Comparator: Placebo + SOC; Participants receive placebo to pembrolizumab (saline) IV Q3W plus SOC chemotherapy with cisplatin 80 mg/m^2 IV Q3W and 5-FU 800 mg/m^2/day continuous IV infusion on Days 1 to 5 (120 hours) Q3W. All treatments will be administered on an outpatient basis beginning on Day 1 of each 3-week dosing cycle.	Drug: Cisplatin; 80 mg/m^2 administered IV Q3W on Day 1 of each 3-week cycle. Duration of cisplatin treatment will be capped at 6 doses.; Drug: Placebo; Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.; Drug: 5-FU; 800 mg/m^2/day (4000 mg/m^2 total per cycle) administered as continuous IV infusion on Days 1 to 5 (120 hours) of each 3-week cycle, or per local standard for 5-FU administration, up to 35 administrations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) in Participants With Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Are Programmed Cell Death-Ligand 1 (PD-L1) Biomarker-Positive (Combined Positive Score [CPS] ≥10)	Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the Intent-To-Treat (ITT) population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
OS in Participants With ESCC	Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who had ESCC.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
OS in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
OS in All Participants	Overall survival was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS is reported here for all participants of the ITT population (all randomized).	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) As Assessed By Investigator in Participants With ESCC	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who had ESCC.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
PFS Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
PFS Per RECIST 1.1 As Assessed By Investigator in All Participants	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 as assessed by the investigator, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS is reported here for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized).	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC and who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who had ESCC.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by the investigator. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for all participants of the ITT population (all randomized) who were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC and were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
DOR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and who had ESCC.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
DOR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by the investigator, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR is reported here for all participants of the ITT population (all randomized) who had CR or PR, and were PD-L1 CPS ≥10.	Up to approximately 34 months (through Primary Analysis cut-off date of 02-Jul-2020)
Number of Participants With an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm.	Up to approximately 28 months
Number of Participants Discontinuing Study Treatment Due to an AE	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm.	Up to approximately 27 months
Change From Baseline To Week 18 in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Global Health Status/Quality of Life (GHS/QoL) Combined Score in All Participants	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants.	Baseline, Week 18
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC and who were PD-L1 CPS ≥10.	Baseline, Week 18
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants With ESCC	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who had ESCC.	Baseline, Week 18
Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question "How would you rate your overall health during the past week?" (Item 29) and the Quality of Life (QoL) question "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was reported by treatment arm as a pre-specified secondary analysis for all participants who were PD-L1 CPS ≥10.	Baseline, Week 18
Change From Baseline in the EORTC Quality Of Life Questionnaire Oesophageal Module (QLQ-OES18) Subscale Scores in All Participants	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores represent a higher ("worse") level of symptoms. Per protocol, change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for all participants in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.	Baseline, Week 18
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.	Baseline, Week 18
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants With ESCC	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants with ESCC in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.	Baseline, Week 18
Change From Baseline in the EORTC QLQ-OES18 Subscale Scores in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)	The EORTC QLQ-OES18 is a disease-specific questionnaire developed and validated to address measurements specific to esophageal cancer and contains 18 items assessing symptoms of dysphagia, pain, reflux symptoms, eating restrictions, anxiety, dry mouth, taste, body image, and hair loss. For the purposes of this study, the Dysphagia subscale (three items), Pain subscale (three items), and Reflux subscale (two items) were evaluated. All subscale items were scored using a four-point Likert scale with the following response choices: 1=not at all, 2=a little, 3=quite a bit, 4=very much. Raw scores for the subscales were standardized into a range of 0 to 100 by linear transformation, with higher symptom scores representing a higher ("worse") level of symptoms. Change from baseline to Week 18 in the Dysphagia, Pain, and Reflux subscales was reported for participants who were PD-L1 CPS≥10 in each treatment arm. Negative changes from baseline indicate a decrease in symptom severity.	Baseline, Week 18

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Ogata T, Ishihara R, Goto M, Baba H, Nishina T, Han S, Sakata T, Yatsuzuka N, Doi T, Kato K. First-line pembrolizumab + chemotherapy in Japanese patients with advanced/metastatic esophageal cancer from KEYNOTE-590. Esophagus. 2022 Oct;19(4):683-692. doi: 10.1007/s10388-022-00920-x. Epub 2022 Jun 7.
• Zhu Y, Liu K, Ding D, Zhou Y, Peng L. Pembrolizumab Plus Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A Cost-Effectiveness Analysis. Adv Ther. 2022 Jun;39(6):2614-2629. doi: 10.1007/s12325-022-02101-9. Epub 2022 Apr 8.
• Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. doi: 10.1016/S0140-6736(21)01234-4. Erratum In: Lancet. 2021 Nov 20;398(10314):1874.
• Kato K, Shah MA, Enzinger P, Bennouna J, Shen L, Adenis A, Sun JM, Cho BC, Ozguroglu M, Kojima T, Kostorov V, Hierro C, Zhu Y, McLean LA, Shah S, Doi T. KEYNOTE-590: Phase III study of first-line chemotherapy with or without pembrolizumab for advanced esophageal cancer. Future Oncol. 2019 Apr;15(10):1057-1066. doi: 10.2217/fon-2018-0609. Epub 2019 Feb 8.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2017
• Primary Completion (Actual): July 2, 2020
• Study Completion (Actual): July 10, 2023

Study Registration Dates

• First Submitted: June 14, 2017
• First Submitted That Met QC Criteria: June 15, 2017
• First Posted (Actual): June 16, 2017

Study Record Updates

• Last Update Posted (Actual): July 27, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Programmed Cell Death-1 (PD1, PD-1),; Programmed Cell Death Receptor Ligand 1 (PDL1, PD-L1); Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 3475-590; 2017-000958-19 (EudraCT Number); 173739 (Registry Identifier: JAPIC-CTI); MK-3475-590 (Other Identifier: Merck); KEYNOTE-590 (Other Identifier: Merck)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No