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

NCT03189719 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-590173739MK-3475-590KEYNOTE-5902017-000958-19
• Study Type: interventional
• Target: 749
• Locations: 25 countries
• Sites: 186

Brief Summary

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. 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. 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.

Conditions

Esophageal Neoplasms

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)

Outcome Measures

Primary Outcomes (7)

• 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

• 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

• 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

• 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

• 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

• 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

• 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).

  Up to approximately 34 months

Secondary Outcomes (18)

• Objective Response Rate (ORR) Per RECIST 1.1 As Assessed By Investigator in All Participants

  Up to approximately 34 months

• ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

  Up to approximately 34 months

• ORR Per RECIST 1.1 As Assessed By Investigator in Participants With ESCC

  Up to approximately 34 months

• ORR Per RECIST 1.1 As Assessed By Investigator in Participants Whose Tumors Are PD-L1 Biomarker-Positive (CPS ≥10)

  Up to approximately 34 months

• Duration of Response (DOR) Per RECIST 1.1 As Assessed By Investigator in All Participants

  Up to approximately 34 months

Study Arms (2)

Pembrolizumab + SOC

EXPERIMENTAL

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; Drug: Cisplatin; Drug: 5-FU

Placebo + SOC

PLACEBO COMPARATOR

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: Placebo; Drug: Cisplatin; Drug: 5-FU

Interventions

Pembrolizumab BIOLOGICAL

200 mg administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

Also known as: MK-3475

Pembrolizumab + SOC

Placebo DRUG

Placebo to pembrolizumab (saline) administered IV Q3W on Day 1 of each 3-week cycle, up to 35 administrations.

Placebo + SOC

Cisplatin DRUG

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.

Pembrolizumab + SOC; Placebo + SOC

5-FU DRUG

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.

Pembrolizumab + SOC; Placebo + SOC

Eligibility Criteria

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

You may qualify if:

• Has histologically- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (189)

Kaiser Permanente Southern California ( Site 0003)

West Los Angeles, California, 90034, United States

Location

The University of Chicago Medical Center ( Site 0001)

Chicago, Illinois, 60637, United States

Location

University of Kansas ( Site 0029)

Westwood, Kansas, 66205, United States

Location

University of Maryland Medical Center ( Site 0013)

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Center ( Site 0009)

Boston, Massachusetts, 02215, United States

Location

Henry Ford Cancer Center ( Site 0018)

Detroit, Michigan, 48202, United States

Location

Washington University School of Medicine ( Site 0031)

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute ( Site 0004)

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College ( Site 0024)

New York, New York, 10065, United States

Location

University Hospitals Cleveland Medical Center ( Site 0002)

Cleveland, Ohio, 44106, United States

Location

UPMC Cancer Center/Hillman Cancer Center ( Site 0015)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Tennessee Medical Center Knoxville ( Site 0017)

Knoxville, Tennessee, 37920, United States

Location

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0603)

Viedma, Río Negro Province, R8500ACE, Argentina

Location

Hospital Aleman ( Site 0605)

Buenos Aires, C1118AAT, Argentina

Location

Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0602)

Buenos Aires, C1264AAA, Argentina

Location

Sanatorio Allende - Cordoba ( Site 0604)

Córdoba, X5000JHQ, Argentina

Location

Hospital Privado Centro Medico Cordoba ( Site 0601)

Córdoba, X5016KEH, Argentina

Location

Blacktown Hospital ( Site 2000)

Blacktown, New South Wales, 2148, Australia

Location

Liverpool Hospital. ( Site 2001)

Liverpool, New South Wales, 2170, Australia

Location

Princess Alexandra Hospital ( Site 2005)

Woolloongabba, Queensland, 4102, Australia

Location

Eastern Health ( Site 2002)

Box Hill, Victoria, 3128, Australia

Location

Peter MacCallum Cancer Centre ( Site 2003)

Melbourne, Victoria, 3000, Australia

Location

CETUS Hospital Dia Oncologia ( Site 0208)

Belo Horizonte, Minas Gerais, 30110-022, Brazil

Location

Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0210)

Recife, Pernambuco, 50070-550, Brazil

Location

Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0209)

Rio de Janeiro, Rio de Janeiro, 20231-050, Brazil

Location

Hospital Sao Vicente de Paulo ( Site 0204)

Passo Fundo, Rio Grande do Sul, 99010-080, Brazil

Location

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0201)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Clinica de Hematologia e Oncologia Viver Ltda ( Site 0211)

Santa Maria, Rio Grande do Sul, 97015-513, Brazil

Location

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto. ( Site 0203)

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

Location

Hospital Alemao Oswaldo Cruz ( Site 0207)

São Paulo, São Paulo, 01323-903, Brazil

Location

Hospital de Clinicas de Porto Alegre ( Site 0200)

Porto Alegre, 90035-903, Brazil

Location

Instituto do Cancer de Sao Paulo - ICESP ( Site 0206)

São Paulo, 01246-000, Brazil

Location

Tom Baker Cancer Centre ( Site 0503)

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute ( Site 0502)

Edmonton, Alberta, T6G 1Z2, Canada

Location

CancerCare Manitoba ( Site 0500)

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Juravinski Cancer Center ( Site 0508)

Hamilton, Ontario, L8V 5C2, Canada

Location

The Ottawa Hospital - Cancer Care ( Site 0501)

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre ( Site 0505)

Toronto, Ontario, M5G 2M9, Canada

Location

CISSS de la Monteregie-Centre ( Site 0504)

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Jewish General Hospital ( Site 0507)

Montreal, Quebec, H3T 1E2, Canada

Location

Hospital Regional de Concepcion Dr. Guillermo Grant Benavente ( Site 1003)

Concepción, 4070038, Chile

Location

Pontificia Universidad Catolica de Chile ( Site 1001)

Santiago, 7620002, Chile

Location

Hospital Clinico Universidad de Chile ( Site 1002)

Santiago, 8380456, Chile

Location

Clinica Alemana de Temuco ( Site 1006)

Temuco, 4810297, Chile

Location

Anhui Provincial Hospital ( Site 0106)

Hefei, Anhui, 230036, China

Location

The First Affiliated Hospital of Anhui Medical University ( Site 0112)

Hefei, Anhui, 230088, China

Location

Peking Union Medical College Hospital ( Site 0123)

Beijing, Beijing Municipality, 100032, China

Location

The First Affiliated Hospital of Xiamen University ( Site 0119)

Xiamen, Fujian, 361000, China

Location

Guangdong General Hospital ( Site 0103)

Guangzhou, Guangdong, 510120, China

Location

The Affiliated Tumour Hospital of Harbin Medical University ( Site 0102)

Harbin, Heilongjiang, 150081, China

Location

Tongji Medical College Huazhong University of Science and Technology ( Site 0109)

Wuhan, Hubei, 430030, China

Location

Hunan Cancer Hospital ( Site 0105)

Changsha, Hunan, 410013, China

Location

PLA Cancer Centre of Nanjing Bayi Hospital ( Site 0110)

Nanjing, Jiangsu, 210002, China

Location

Zhongda Hospital Southeast University ( Site 0125)

Nanjing, Jiangsu, 210009, China

Location

Jilin Cancer Hospital ( Site 0101)

Changchun, Jilin, 130012, China

Location

The First Affiliated Hospital of Xi an Jiaotong University ( Site 0120)

Xi'an, Shannxi, 710061, China

Location

Zhejiang Cancer Hospital ( Site 0116)

Hangzhou, Zhejiang, 310022, China

Location

Beijing Cancer Hospital ( Site 0100)

Beijing, 100142, China

Location

Fujian Provincial Cancer Hospital ( Site 0104)

Fuzhou, 350014, China

Location

Shanghai Chest Hospital ( Site 0111)

Shanghai, 200030, China

Location

Fudan University Shanghai Cancer Center ( Site 0108)

Shanghai, 200032, China

Location

Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0114)

Shanghai, 200127, China

Location

Henan Cancer Hospital ( Site 0107)

Zhengzhou, 450008, China

Location

Rodrigo Botero SAS ( Site 2703)

Medellín, Antioquia, 050030, Colombia

Location

Oncomedica S.A. ( Site 2701)

Montería, Departamento de Córdoba, 230018, Colombia

Location

CIMCA Centro de Investigacion y Manejo del Cancer ( Site 2600)

San José, 10103, Costa Rica

Location

Policlinico San Bosco ( Site 2602)

San José, 10103, Costa Rica

Location

ICIMED - Instituto de Investigacion en Ciencias Medicas ( Site 2601)

San José, 10108, Costa Rica

Location

Rigshospitalet ( Site 2301)

Copenhagen, 2100, Denmark

Location

Odense Universitetshospital ( Site 2300)

Odense, 5000, Denmark

Location

Centre Leon Berard ( Site 0307)

Lyon, Cedex 8, 69373, France

Location

CHU Brest - Institut de Cancerologie et d Hematologie ( Site 0305)

Brest, 29200, France

Location

Centre Francois Baclesse ( Site 0310)

Caen, 14076, France

Location

Centre Oscar Lambret ( Site 0304)

Lille, 59020, France

Location

Institut du Cancer de Montpellier ( Site 0306)

Montpellier, 34298, France

Location

CHU de Nantes - Hotel Dieu ( Site 0303)

Nantes, 44093, France

Location

Institut Mutualiste Montsouris ( Site 0300)

Paris, 75014, France

Location

CHU de Saint Etienne Hopital Nord ( Site 0309)

Saint-Etienne, 42055, France

Location

Staedtisches Klinikum Dresden ( Site 1507)

Dresden, 01067, Germany

Location

Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 1502)

Hamburg, 20249, Germany

Location

Universitaetsklinikum Leipzig ( Site 1501)

Leipzig, 04103, Germany

Location

Klinikum Ludwigsburg ( Site 1509)

Ludwigsburg, 71640, Germany

Location

Universitatsklinikum Mannheim GmbH ( Site 1504)

Mannheim, 68167, Germany

Location

Klinik fuer Haematologie. Onkologie und Gastroenterologie ( Site 1508)

Mönchengladbach, 41063, Germany

Location

III. Medizinische Klinik Klinikum rechts der Isar ( Site 1506)

München, 81675, Germany

Location

Centro de Investigacion Oncologica ( Site 1402)

Guatemala City, 01010, Guatemala

Location

Oncomedica ( Site 1400)

Guatemala City, 01010, Guatemala

Location

Grupo Medico Angeles ( Site 1401)

Guatemala City, 01015, Guatemala

Location

Medi-K Cayala ( Site 1404)

Guatemala City, 01016, Guatemala

Location

Centro Regional de Sub Especialidades Medicas SA ( Site 1403)

Quetzaltenango, 09001, Guatemala

Location

Humanity Health Research Centre ( Site 1603)

Hong Kong, Hong Kong

Location

Pamela Youde Nethersole Eastern Hospital ( Site 1601)

Hong Kong, Hong Kong

Location

Princess Margaret Hospital. ( Site 1602)

Hong Kong, Hong Kong

Location

Queen Mary Hospital ( Site 1600)

Hong Kong, Hong Kong

Location

Aichi Cancer Center Hospital ( Site 0902)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 0908)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 0901)

Matsuyama, Ehime, 791-0280, Japan

Location

Hokkaido University Hospital ( Site 0916)

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center ( Site 0913)

Akashi, Hyōgo, 673-8558, Japan

Location

Kobe City Medical Center General Hospital ( Site 0929)

Kobe, Hyōgo, 650-0047, Japan

Location

Ibaraki Prefectural Central Hospital ( Site 0918)

Kasama, Ibaraki, 309-1793, Japan

Location

University of Tsukuba Hospital ( Site 0910)

Tsukuba, Ibaraki, 305-8576, Japan

Location

Kagawa University Hospital ( Site 0915)

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

Location

St. Marianna University School of Medicine Hospital ( Site 0903)

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kanagawa Cancer Center ( Site 0921)

Yokohama, Kanagawa, 241-8515, Japan

Location

Oita University Hospital ( Site 0930)

Yufu, Oita Prefecture, 879-5593, Japan

Location

Kansai Medical University Hospital ( Site 0931)

Hirakata, Osaka, 573-1191, Japan

Location

Kindai University Hospital ( Site 0917)

Sayama, Osaka, 589-8511, Japan

Location

Osaka University Hospital ( Site 0911)

Suita, Osaka, 565-0871, Japan

Location

Osaka Medical College Hospital ( Site 0925)

Takatsuki, Osaka, 569-8686, Japan

Location

Saitama Cancer Center ( Site 0926)

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute ( Site 0914)

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Kyorin University Hospital ( Site 0905)

Mitaka, Tokyo, 181-8611, Japan

Location

Chiba University Hospital ( Site 0909)

Chiba, 260-8677, Japan

Location

Chiba Cancer Center ( Site 0900)

Chiba, 260-8717, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 0906)

Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital ( Site 0922)

Fukuoka, 812-8582, Japan

Location

Gifu University Hospital ( Site 0920)

Gifu, 501-1194, Japan

Location

Kumamoto University Hospital ( Site 0919)

Kumamoto, 860-8556, Japan

Location

Niigata Cancer Center Hospital ( Site 0924)

Niigata, 951-8566, Japan

Location

Osaka International Cancer Institute ( Site 0923)

Osaka, 541-8567, Japan

Location

Osaka General Medical Center ( Site 0912)

Osaka, 558-8558, Japan

Location

National Cancer Center Hospital ( Site 0907)

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 0904)

Tokyo, 135-8550, Japan

Location

Keio University Hospital ( Site 0927)

Tokyo, 160-8582, Japan

Location

Beacon International Specialist Centre ( Site 1803)

Petaling Jaya, Selangor, 46050, Malaysia

Location

Hospital Kuala Lumpur ( Site 1805)

Kuala Lumpur, 50586, Malaysia

Location

University Malaya Medical Centre ( Site 1802)

Kuala Lumpur, 59100, Malaysia

Location

Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 1702)

Arequipa, 04000, Peru

Location

Hospital Nacional Guillermo Almenara Irigoyen ( Site 1701)

Lima, 15033, Peru

Location

Instituto Nacional de Enfermedades Neoplasicas ( Site 1705)

Lima, 15038, Peru

Location

S C Pelican Impex SRL ( Site 2403)

Oradea, Bihor County, 410469, Romania

Location

S.C. Radiotherapy Center Cluj S.R.L ( Site 2407)

Comuna Floresti, Cluj, 407280, Romania

Location

S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 2404)

Craiova, Dolj, 200347, Romania

Location

S.C.Focus Lab Plus S.R.L ( Site 2401)

Bucharest, Sector 2, 021389, Romania

Location

S C Oncocenter Oncologie Medicala S R L ( Site 2405)

Timișoara, Timiș County, 300166, Romania

Location

S.C.Gral Medical S.R.L ( Site 2406)

Bucharest, 031422, Romania

Location

Spitalul Clinic Judetean De Urgenta Constanta ( Site 2402)

Constanța, 900591, Romania

Location

SBHCI RCOD of MHC RB ( Site 0407)

Ufa, Bashkortostan Republic, 450054, Russia

Location

Leningrad Regional Oncology Center ( Site 0405)

Saint Petersburg, Vsevolzhsk District, 188663, Russia

Location

National Medical and Surgical Center n.a. N.I.Pirogov ( Site 0402)

Moscow, 105203, Russia

Location

N.N. Blokhin NMRCO ( Site 0401)

Moscow, 115478, Russia

Location

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0406)

Saint Petersburg, 197758, Russia

Location

St Petersburg City Clinical Oncology Dispensary ( Site 0409)

Saint Petersburg, 198255, Russia

Location

Tomsk Scientific Research Institute of Oncology ( Site 0403)

Tomsk, 634028, Russia

Location

Cancer Care Langenhoven Drive Oncology Centre ( Site 2501)

Port Elizabeth, Eastern Cape, 6045, South Africa

Location

The Medical Oncology Centre of Rosebank ( Site 2506)

Johannesburg, Gauteng, 2196, South Africa

Location

WITS Clinical Research CMJAH Clinical Trial Site ( Site 2500)

Parktown, Gauteng, 2193, South Africa

Location

The Oncology Centre ( Site 2502)

Durban, KwaZulu-Natal, 4091, South Africa

Location

Cape Town Oncology Trials Pty Ltd ( Site 2508)

Cape Town, Western Cape, 7570, South Africa

Location

Outeniqua Cancercare Oncology Unit ( Site 2504)

George, Western Cape, 6530, South Africa

Location

Clinton Oncology Centre ( Site 2505)

Alberton, 1448, South Africa

Location

National Cancer Center ( Site 1304)

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

Location

Chonnam National University Hwasun Hospital ( Site 1305)

Hwasun Gun, Jeollanam-do, 58128, South Korea

Location

Seoul National University Cancer Hospital ( Site 1301)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 1302)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 1303)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 1300)

Seoul, 06351, South Korea

Location

Hosp. Gral. Universitari Germans Trias i Pujol ( Site 0701)

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Central de Asturias ( Site 0708)

Oviedo, Principality of Asturias, 33011, Spain

Location

Hospital Universitari Vall d Hebron ( Site 0702)

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia ( Site 0706)

Córdoba, 14004, Spain

Location

Hospital Ramon y Cajal ( Site 0703)

Madrid, 28034, Spain

Location

Hospital Universitario La Paz ( Site 0700)

Madrid, 28046, Spain

Location

Complejo Hospitalario Virgen De La Victoria ( Site 0705)

Málaga, 29010, Spain

Location

Chang Gung Med Foundation. Kaohsiung Branch ( Site 1906)

Kaohsiung City, 833, Taiwan

Location

Taipei Medical University Shuang Ho Hospital ( Site 1908)

New Taipei City, 235, Taiwan

Location

China Medical University Hospital ( Site 1904)

Taichung, 404, Taiwan

Location

Kuang Tien General Hospital ( Site 1909)

Taichung, 43303, Taiwan

Location

National Cheng Kung University Hospital ( Site 1905)

Tainan, 704, Taiwan

Location

Chi Mei Medical Center Liuying ( Site 1907)

Tainan, 736, Taiwan

Location

National Taiwan University Hospital ( Site 1900)

Taipei, 10002, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center ( Site 1902)

Taipei, 11259, Taiwan

Location

Chang Gung Medical Foundation. Linkou ( Site 1903)

Taoyuan District, 333, Taiwan

Location

Bumrungrad International Hospital ( Site 2203)

Bangkok, 10110, Thailand

Location

Chulalongkorn Hospital ( Site 2201)

Bangkok, 10330, Thailand

Location

Ramathibodi Hospital. ( Site 2202)

Bangkok, 10330, Thailand

Location

Phramongkutklao Hospital ( Site 2205)

Bangkok, 10400, Thailand

Location

Songklanagarind Hospital ( Site 2204)

Songkhla, 90110, Thailand

Location

Adana Sehir Hastanesi ( Site 0802)

Adana, 01370, Turkey (Türkiye)

Location

Ankara Sehir Hastanesi ( Site 0808)

Ankara, 06800, Turkey (Türkiye)

Location

Istanbul Medeniyet Universitesi Goztepe EAH ( Site 0807)

Istanbul, 34093, Turkey (Türkiye)

Location

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0804)

Istanbul, 34098, Turkey (Türkiye)

Location

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 0801)

Istanbul, 34899, Turkey (Türkiye)

Location

Medical Park Izmir Hastanesi ( Site 0800)

Izmir, 35575, Turkey (Türkiye)

Location

Inonu Universitesi Turgut Ozal Tip Merkezi ( Site 0803)

Malatya, 44280, Turkey (Türkiye)

Location

Lothian University Hospitals NHS Trust ( Site 1101)

Edinburgh, Mid Lothian, EH4 2XU, United Kingdom

Location

St Luke's Cancer Centre ( Site 1102)

Guildford, GU2 7XX, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 1100)

Manchester, M20 4BX, United Kingdom

Location

Related Publications (7)

• Mansoor W, Joo S, Norquist JM, Kato K, Sun JM, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Sunpaweravong P, Alsina M, Goekkurt E, Suryawanshi S, Shah S, Shen L. Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer. Oncologist. 2024 Oct 3;29(10):e1324-e1335. doi: 10.1093/oncolo/oyae087.

  PMID: 38815152 DERIVED

• Kato K, Kojima T, Hara H, Tsuji A, Yasui H, Muro K, Satoh T, Ogata T, Ishihara R, Goto M, Baba H, Nishina T, Han S, Iwakami K, Yatsuzuka N, Doi T. First-line pembrolizumab plus chemotherapy for advanced/metastatic esophageal cancer: 1-year extended follow-up in the Japanese subgroup of the phase 3 KEYNOTE-590 study. Esophagus. 2024 Jul;21(3):306-318. doi: 10.1007/s10388-024-01053-z. Epub 2024 Apr 12.

  PMID: 38607538 DERIVED

• Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.

  PMID: 37139963 DERIVED

• 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.

  PMID: 35668304 DERIVED

• 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.

  PMID: 35394255 DERIVED

• 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.

  PMID: 34454674 DERIVED

• 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.

  PMID: 30735435 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Esophageal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Cisplatin; Fluorouracil

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

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

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: June 16, 2017
• Study Start: July 25, 2017
• Primary Completion: July 2, 2020
• Study Completion: July 10, 2023
• Last Updated: October 15, 2024
• Results First Posted: July 6, 2021

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

CO (2); ZA (7); GB (3); KR (6); HK (4); CA (8); RU (7); RO (7); ES (7); TH (5); PE (3); TU (7); US (12); CL (4); CN (19); DE (7); AR (5); FR (8); MY (3); JP (31); TW (9); AU (5); BR (10); GU (5); DK (2)