Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants With Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-585/KEYNOTE-585)
Gastric Cancer, Gastroesophageal Junction Cancer

About this trial
This is an interventional treatment trial for Gastric Cancer focused on measuring Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Eligibility Criteria
Inclusion Criteria:
- Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease.
- Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice.
- Is willing to provide tissue from a tumor lesion at baseline and at time of surgery.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment.
- Has adequate organ function.
- Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy.
- Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
- Has life expectancy of greater than 6 months.
Exclusion Criteria:
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
- Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], necrosis factor receptor superfamily member 9 [CD137]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial.
- Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy.
- 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 14 days prior the first dose of study treatment.
- Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded.
- Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients.
- Has an active autoimmune disease that has required systemic treatment in past 2 years.
- 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).
- Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater.
- Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy.
- Has had an allogenic tissue/solid organ transplant.
- Has received a live vaccine within 30 days prior to the first dose of study treatment.
Sites / Locations
- City of Hope ( Site 0005)
- Yale Cancer Center ( Site 0016)
- Georgetown University ( Site 0015)
- Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0018)
- The University of Chicago Medical Center ( Site 0004)
- Roswell Park Cancer Institute ( Site 0001)
- Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0019)
- Memorial Sloan Kettering ( Site 0024)
- Weill Cornell Medical Center ( Site 0023)
- University of Rochester ( Site 0011)
- Fox Chase Cancer Center ( Site 0006)
- Temple University Hospital ( Site 0026)
- University of Utah, Huntsman Cancer Institute ( Site 0012)
- Virginia Cancer Specialists, PC ( Site 0010)
- Institut Jules Bordet ( Site 0480)
- Hopital Erasme ULB ( Site 0484)
- UCL Saint Luc ( Site 0479)
- Grand Hopital de Charleroi ( Site 0478)
- CHU de Liege ( Site 0482)
- CHU UCL Namur Site de Godinne ( Site 0485)
- UZ Gent ( Site 0486)
- UZ Leuven ( Site 0483)
- AZ Groeninge ( Site 0481)
- Instituto do Cancer do Ceara ( Site 0311)
- Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0308)
- CEPON - Centro de Pesquisas Oncologicas ( Site 0302)
- Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0301)
- Hospital de Base de Sao Jose de Rio Preto ( Site 0304)
- Instituto Nacional Do Cancer Jose Alencar Gomes Da Silva ( Site 0307)
- Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0305)
- Hospital Israelita Albert Einstein ( Site 0309)
- Cross Cancer Institute ( Site 0033)
- Moncton Hospital - Horizon Health Network ( Site 0038)
- Sunnybrook Research Institute ( Site 0032)
- CISSS de la Monteregie-Centre ( Site 0039)
- CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0040)
- Jewish General Hospital ( Site 0034)
- CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0035)
- CHU de Quebec - Hotel-Dieu de Quebec ( Site 0042)
- Instituto Clinico del Sur. ICOS ( Site 0290)
- Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0299)
- Fundacion Arturo Lopez Perez FALP ( Site 0286)
- Pontificia Universidad Catolica de Chile ( Site 0285)
- Hospital Clinico Universidad de Chile ( Site 0287)
- Beijing Cancer Hospital ( Site 0221)
- Zhejiang Cancer Hospital ( Site 0231)
- Sir Run Run Shaw Hospital ( Site 0233)
- SA Pohja-Eesti Regionaalhaigla ( Site 0526)
- Hopital Prive Jean Mermoz ( Site 0462)
- Institut Paoli Calmettes ( Site 0472)
- CHU Reims - Hopital Robert Debre ( Site 0465)
- CHU Brest - Institut de Cancerologie et d Hematologie ( Site 0474)
- CHU Toulouse - Hopital Rangueil ( Site 0470)
- Institut du Cancer de Montpellier ( Site 0473)
- Centre Eugene Marquis ( Site 0466)
- Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0469)
- CHRU Lille - Hopital Claude Huriez ( Site 0461)
- CHU Poitiers - Pole Regional de Cancerologie ( Site 0467)
- CHU Hopital Saint Antoine ( Site 0471)
- Institut Mutualiste Montsouris ( Site 0463)
- Klinikum Esslingen GmbH ( Site 0453)
- Universitaetsklinikum Freiburg ( Site 0450)
- Klinikum der Universitaet in Muenchen ( Site 0446)
- Medizinische Hochschule Hannover ( Site 0449)
- Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 0445)
- Medizinische klinilk und Poliklinik Johannes Gutenberg Univ ( Site 0455)
- Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 0448)
- Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 0454)
- Integra Cancer Institute ( Site 0262)
- Grupo Medico Angeles ( Site 0261)
- Centro Medico Integral De Cancerología (CEMIC) ( Site 0260)
- Soroka University M.C ( Site 0385)
- Meir medical center ( Site 0386)
- Sourasky Medical Center. ( Site 0382)
- Rambam Health Care Campus ( Site 0381)
- Hadassah Medical Center. Ein Kerem ( Site 0383)
- Rabin-Medical Center ( Site 0384)
- Sheba Medical center ( Site 0387)
- IRCCS Istituto Oncologico Veneto ( Site 0431)
- Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0430)
- Istituto Clinico Humanitas Research Hospital ( Site 0432)
- IRCCS Policlinico San Donato ( Site 0433)
- Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0429)
- Seconda Universita Napoli ( Site 0436)
- A.O.U. Santa Maria della Misericordia di Udine ( Site 0434)
- Aichi Cancer Center Hospital ( Site 0165)
- National Cancer Center Hospital East ( Site 0178)
- National Hospital Organization Shikoku Cancer Center ( Site 0186)
- Hokkaido University Hospital ( Site 0160)
- Hyogo Cancer Center ( Site 0182)
- Kobe University Hospital ( Site 0188)
- Kobe City Medical Center General Hospital ( Site 0181)
- Ibaraki Prefectural Central Hospital ( Site 0177)
- Iwate Medical University Hospital ( Site 0184)
- St. Marianna University School of Medicine Hospital ( Site 0187)
- Kanagawa Cancer Center ( Site 0167)
- Kansai Medical University Hospital ( Site 0190)
- Osaka University Hospital ( Site 0162)
- Osaka Medical College Hospital ( Site 0168)
- Saitama Cancer Center ( Site 0170)
- Shizuoka Cancer Center Hospital and Research Institute ( Site 0176)
- Chiba Cancer Center ( Site 0180)
- National Hospital Organization Kyushu Cancer Center ( Site 0172)
- Kyushu University Hospital ( Site 0173)
- Gifu University Hospital ( Site 0166)
- Hiroshima City Hiroshima Citizens Hospital ( Site 0171)
- Kochi Health Sciences Center ( Site 0189)
- Kumamoto University Hospital ( Site 0164)
- Niigata Cancer Center Hospital ( Site 0169)
- Osaka International Cancer Institute ( Site 0161)
- Osaka General Medical Center ( Site 0159)
- National Cancer Center Hospital ( Site 0179)
- Tokyo Metropolitan Komagome Hospital ( Site 0183)
- The Cancer Institute Hospital of JFCR ( Site 0185)
- Toyama Prefectural Central Hospital ( Site 0163)
- Chonnam National University Hwasun Hospital ( Site 0083)
- Seoul National University Bundang Hospital ( Site 0085)
- Kyungpook National University Chilgok Hospital ( Site 0089)
- Gachon University Gil Medical Center ( Site 0087)
- Korea University Anam Hospital ( Site 0084)
- Seoul National University Hospital -SNUH- ( Site 0080)
- Severance Hospital Yonsei University Health System ( Site 0081)
- Asan Medical Center ( Site 0082)
- Gangnam Severance Hospital ( Site 0088)
- SMG-SNU BORAMAE Medical Center ( Site 0086)
- Riga East Clinical University Hospital ( Site 0550)
- LSMUL Kauno Klinikos ( Site 0570)
- Nacionalinis Vezio Institutas ( Site 0569)
- Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 0568)
- Hospital Kuala Lumpur ( Site 0146)
- University Malaya Medical Centre ( Site 0143)
- St. Luke s Medical Center ( Site 0622)
- Wojewodzki Szpital Specjalistyczny we Wroclawiu ( Site 0358)
- Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 0351)
- Szpital Uniwersytecki w Krakowie ( Site 0352)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0349)
- Mazowiecki Szpital Onkologiczny ( Site 0363)
- Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 0353)
- Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0354)
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0361)
- SPZOZ WSS nr 3 w Rybniku ( Site 0357)
- Kaluga Regional Clinical Oncology Center ( Site 0345)
- SBHI Leningrad Regional Clinical Hospital ( Site 0496)
- National Medical and Surgical Center n.a. N.I.Pirogov ( Site 0338)
- Blokhin National Medical Oncology ( Site 0494)
- Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0344)
- Leningrad Regional Oncology Center ( Site 0335)
- City clinical oncological dispensary ( Site 0336)
- Tomsk Scientific Research Institute of Oncology ( Site 0337)
- National University Hospital ( Site 0095)
- National Cancer Centre Singapore ( Site 0097)
- Oncocare Cancer Centre ( Site 0096)
- Taipei Medical University Shuang Ho Hospital ( Site 0068)
- National Cheng Kung University Hospital ( Site 0067)
- National Taiwan University Hospital ( Site 0063)
- Mackay Memorial Hospital ( Site 0065)
- Koo Foundation Sun Yat-Sen Cancer Center ( Site 0066)
- Chang Gung Medical Foundation. Linkou ( Site 0064)
- City Clinical Hosp.4 of DCC ( Site 0325)
- MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 0589)
- Ivano-Frankivsk Regional Oncology Clinical Dispensary ( Site 0321)
- Communal non profit enterprise Regional Clinical Oncology Center ( Site 0591)
- National Cancer Institute of the MoH of Ukraine ( Site 0319)
- Kyiv City Clinical Oncology Center ( Site 0590)
- University Hospitals Bristol NHS Foundation Trust ( Site 0407)
- Ninewells Hospital and Medical School ( Site 0406)
- Royal Free London NHS Foundation Trust ( Site 0403)
- The Royal Marsden Foundation Trust ( Site 0405)
- Imperial College Healthcare NHS Trust ( Site 0402)
- Royal Marsden NHS Foundation Trust ( Site 0400)
- The Christie NHS Foundation Trust ( Site 0397)
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Pembrolizumab+Chemotherapy
Placebo+Chemotherapy
Pembrolizumab+FLOT Cohort
Placebo+FLOT Cohort
Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles.
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle. Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.
FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion Day 1 Q3W PLUS docetaxel 50 mg/m^2, oxaliplatin 85 mg/m^2, 5FU 2600 mg/m^2, and leucovorin 200 mg/m^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles.
Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations). Adjuvant: 4 to 10 weeks postsurgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m^2 via IV infusion, oxaliplatin 85 mg/m^2 via IV infusion, 5FU 2600 mg/m^2 via IV infusion, and leucovorin 200 mg/m^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles.