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)

NCT03221426 | Completed Phase 3 Results DMC FDA Drug

• 7 other identifiers: 3475-585MK-3475-585173786KEYNOTE-585PHRR200226-0025342023-509595-42-002023-509595-42
• Study Type: interventional
• Target: 1,007
• Locations: 24 countries
• Sites: 171

Brief Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that:

• Neoadjuvant and adjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab is superior to neoadjuvant and adjuvant placebo plus chemotherapy, followed by adjuvant placebo in terms of Event-free Survival (EFS) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), and
• Neoadjuvant pembrolizumab plus chemotherapy is superior to neoadjuvant placebo plus chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery. With Amendment 10, upon study completion, participants will be discontinued and may be enrolled in an extension study.

Conditions

Gastric Cancer; Gastroesophageal Junction Cancer

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (5)

• Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  EFS was based on RECIST 1.1 as assessed by the investigator and was defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who were disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who were confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), were not considered EFS events.

  Up to approximately 75 months

• Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  PathCR rate was defined as the percentage of participants having a pathCR based on central review. pathCR was defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes. The percentage of participants having pathCR was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.

  Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18)

• Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  OS was defined as the time from randomization to death due to any cause. OS was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.

  Up to approximately 75 months

• Number of Participants Who Experienced One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE was presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.

  Up to approximately 70 months

• Number of Participants Who Discontinued Study Treatment Due to an AE - Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE was presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.

  Up to approximately 17 months

Secondary Outcomes (5)

• Number of Participants Who Experienced One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 89 months

• Number of Participants Who Discontinued Study Treatment Due to an AE - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 17 months

• Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms

  Up to approximately 75 months

• Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 75 months

• Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts

  Up to approximately 75 months

Study Arms (4)

Pembrolizumab + XP/FP

EXPERIMENTAL

XP=cisplatin+capecitabine and FP=cisplatin+5-fluorouracil. 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 IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2 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 IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 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 IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by pembrolizumab monotherapy 200 mg IV infusion on Day 1 Q3W for up to 11 additional cycles.

Biological: Pembrolizumab; Drug: Cisplatin; Drug: Capecitabine; Drug: 5-fluorouracil

Placebo + XP/FP

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: Cisplatin; Drug: Capecitabine; Drug: 5-fluorouracil

Pembrolizumab+FLOT Cohort

EXPERIMENTAL

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.

Biological: Pembrolizumab; Drug: 5-fluorouracil; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Leucovorin

Placebo+FLOT Cohort

PLACEBO COMPARATOR

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.

Drug: Placebo; Drug: 5-fluorouracil; Drug: Docetaxel; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + XP/FP; Pembrolizumab+FLOT Cohort

Placebo DRUG

IV infusion

Also known as: Normal saline solution

Placebo + XP/FP; Placebo+FLOT Cohort

Cisplatin DRUG

IV infusion

Also known as: PLATINOL®

Pembrolizumab + XP/FP; Placebo + XP/FP

Docetaxel DRUG

IV infusion

Also known as: TAXOTERE®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

Capecitabine DRUG

Oral tablets

Also known as: XELODA®

Pembrolizumab + XP/FP; Placebo + XP/FP

5-fluorouracil DRUG

IV infusion

Also known as: ADRUCIL®, 5FU

Pembrolizumab + XP/FP; Pembrolizumab+FLOT Cohort; Placebo + XP/FP; Placebo+FLOT Cohort

Oxaliplatin DRUG

IV infusion

Also known as: ELOXATIN®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

Leucovorin DRUG

IV infusion

Also known as: WELLCOVORIN®

Pembrolizumab+FLOT Cohort; Placebo+FLOT Cohort

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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 MSD pembrolizumab (MK-3475) clinical study.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (171)

City of Hope ( Site 0005)

Duarte, California, 91010, United States

Location

Yale Cancer Center ( Site 0016)

New Haven, Connecticut, 06520, United States

Location

Georgetown University ( Site 0015)

Washington D.C., District of Columbia, 20007, United States

Location

Northwestern University - Robert H. Lurie Comprehensive Cancer Center ( Site 0018)

Chicago, Illinois, 60611, United States

Location

The University of Chicago Medical Center ( Site 0004)

Chicago, Illinois, 60637, United States

Location

Roswell Park Cancer Institute ( Site 0001)

Buffalo, New York, 14263, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0019)

New York, New York, 10016, United States

Location

Memorial Sloan Kettering ( Site 0024)

New York, New York, 10065, United States

Location

Weill Cornell Medical Center ( Site 0023)

New York, New York, 10065, United States

Location

University of Rochester ( Site 0011)

Rochester, New York, 14642, United States

Location

Fox Chase Cancer Center ( Site 0006)

Philadelphia, Pennsylvania, 19111, United States

Location

Temple University Hospital ( Site 0026)

Philadelphia, Pennsylvania, 19140, United States

Location

University of Utah, Huntsman Cancer Institute ( Site 0012)

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists, PC ( Site 0010)

Fairfax, Virginia, 22031, United States

Location

Institut Jules Bordet ( Site 0480)

Brussels, Bruxelles-Capitale, Region de, 1000, Belgium

Location

Hopital Erasme ULB ( Site 0484)

Brussels, Bruxelles-Capitale, Region de, 1070, Belgium

Location

UCL Saint Luc ( Site 0479)

Brussels, Bruxelles-Capitale, Region de, 1200, Belgium

Location

Grand Hopital de Charleroi ( Site 0478)

Charleroi, Hainaut, 6000, Belgium

Location

CHU de Liege ( Site 0482)

Liège, Liege, 4000, Belgium

Location

CHU UCL Namur Site de Godinne ( Site 0485)

Yvoir, Namur, 5530, Belgium

Location

UZ Gent ( Site 0486)

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

UZ Leuven ( Site 0483)

Leuven, Vlaams-Brabant, 3000, Belgium

Location

AZ Groeninge ( Site 0481)

Kortrijk, West-Vlaanderen, 8500, Belgium

Location

Instituto do Cancer do Ceara ( Site 0311)

Fortaleza, Ceará, 60430-230, Brazil

Location

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0308)

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

Location

CEPON - Centro de Pesquisas Oncologicas ( Site 0302)

Florianópolis, Santa Catarina, 88034-000, Brazil

Location

Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0301)

Barretos, São Paulo, 14784-400, Brazil

Location

Hospital de Base de Sao Jose de Rio Preto ( Site 0304)

Sao Jose Rio Preto, São Paulo, 15090-000, Brazil

Location

Instituto Nacional Do Cancer Jose Alencar Gomes Da Silva ( Site 0307)

Rio de Janeiro, 20230-130, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0305)

São Paulo, 01246-000, Brazil

Location

Hospital Israelita Albert Einstein ( Site 0309)

São Paulo, 05652-900, Brazil

Location

Cross Cancer Institute ( Site 0033)

Edmonton, Alberta, T6G 1Z2, Canada

Location

Moncton Hospital - Horizon Health Network ( Site 0038)

Moncton, New Brunswick, E1C 6Z8, Canada

Location

Sunnybrook Research Institute ( Site 0032)

Toronto, Ontario, M4N 3M5, Canada

Location

CISSS de la Monteregie-Centre ( Site 0039)

Greenfield Park, Quebec, J4V 2H1, Canada

Location

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0040)

Montreal, Quebec, H1T 2M4, Canada

Location

Jewish General Hospital ( Site 0034)

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Quebec - Hotel-Dieu de Quebec ( Site 0042)

Québec, Quebec, G1R 2J6, Canada

Location

CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0035)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0299)

Rancagua, Lbtdr Gen Bernardo O Higgins, 2820000, Chile

Location

Fundacion Arturo Lopez Perez FALP ( Site 0286)

Santiago, Region M. de Santiago, 7500921, Chile

Location

Pontificia Universidad Catolica de Chile ( Site 0285)

Santiago, Region M. de Santiago, 8330032, Chile

Location

Hospital Clinico Universidad de Chile ( Site 0287)

Santiago, Region M. de Santiago, 8380456, Chile

Location

Instituto Clinico del Sur. ICOS ( Site 0290)

Temuco, Región de la Araucanía, 4810469, Chile

Location

Beijing Cancer Hospital ( Site 0221)

Beijing, Beijing Municipality, 100142, China

Location

Zhejiang Cancer Hospital ( Site 0231)

Hangzhou, Zhejiang, 310022, China

Location

Sir Run Run Shaw Hospital ( Site 0233)

Hangzhou, Zhejiang, 430030, China

Location

SA Pohja-Eesti Regionaalhaigla ( Site 0526)

Tallinn, Harju, 13419, Estonia

Location

Hopital Prive Jean Mermoz ( Site 0462)

Lyon, Auvergne, 69008, France

Location

Institut Paoli Calmettes ( Site 0472)

Marseille, Bouches-du-Rhone, 13009, France

Location

CHU Reims - Hopital Robert Debre ( Site 0465)

Reims, Champagne-Ardenne, 51092, France

Location

CHU Brest - Institut de Cancerologie et d Hematologie ( Site 0474)

Brest, Finistere, 29200, France

Location

CHU Toulouse - Hopital Rangueil ( Site 0470)

Toulouse, Haute-Garonne, 31059, France

Location

Institut du Cancer de Montpellier ( Site 0473)

Montpellier, Herault, 34298, France

Location

Centre Eugene Marquis ( Site 0466)

Rennes, Ille-et-Vilaine, 35042, France

Location

Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0469)

Saint-Herblain, Loire-Atlantique, 44805, France

Location

CHRU Lille - Hopital Claude Huriez ( Site 0461)

Lille, Nord, 59037, France

Location

CHU Poitiers - Pole Regional de Cancerologie ( Site 0467)

Poitiers, Vienne, 86021, France

Location

CHU Hopital Saint Antoine ( Site 0471)

Paris, 75012, France

Location

Institut Mutualiste Montsouris ( Site 0463)

Paris, 75014, France

Location

Klinikum Esslingen GmbH ( Site 0453)

Esslingen am Neckar, Baden-Wurttemberg, 73730, Germany

Location

Universitaetsklinikum Freiburg ( Site 0450)

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Klinikum der Universitaet in Muenchen ( Site 0446)

Munich, Bavaria, 81377, Germany

Location

Medizinische Hochschule Hannover ( Site 0449)

Hanover, Lower Saxony, 30625, Germany

Location

Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 0445)

Essen, North Rhine-Westphalia, 45136, Germany

Location

Medizinische klinilk und Poliklinik Johannes Gutenberg Univ ( Site 0455)

Mainz, Rhineland-Palatinate, 55131, Germany

Location

Universitaetsklinikum Carl Gustav Carus der TU Dresden ( Site 0448)

Dresden, Saxony, 01307, Germany

Location

Haematologisch-Onkologische Praxis Eppendorf Facharztzentrum Eppendorf - Hope ( Site 0454)

Hamburg, 20249, Germany

Location

Integra Cancer Institute ( Site 0262)

Guatemala City, 01010, Guatemala

Location

Grupo Medico Angeles ( Site 0261)

Guatemala City, 01015, Guatemala

Location

Centro Medico Integral De Cancerología (CEMIC) ( Site 0260)

Quetzaltenango, 09002, Guatemala

Location

Meir medical center ( Site 0386)

Kfar Saba, Central District, 4428164, Israel

Location

Soroka University M.C ( Site 0385)

Beersheba, Southern District, 8410101, Israel

Location

Sourasky Medical Center. ( Site 0382)

Tel Aviv, Tell Abib, 6423906, Israel

Location

Rambam Health Care Campus ( Site 0381)

Haifa, 31096, Israel

Location

Hadassah Medical Center. Ein Kerem ( Site 0383)

Jerusalem, 9112001, Israel

Location

Rabin-Medical Center ( Site 0384)

Petah Tikva, 4941492, Israel

Location

Sheba Medical center ( Site 0387)

Ramat Gan, 5265601, Israel

Location

IRCCS Istituto Oncologico Veneto ( Site 0431)

Padova, Abruzzo, 35128, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0430)

Milan, Lombardy, 20133, Italy

Location

Istituto Clinico Humanitas Research Hospital ( Site 0432)

Rozzano, Milano, 20089, Italy

Location

IRCCS Policlinico San Donato ( Site 0433)

San Donato Milanese, Milano, 20097, Italy

Location

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 0429)

Modena, 41125, Italy

Location

Seconda Universita Napoli ( Site 0436)

Naples, 80131, Italy

Location

A.O.U. Santa Maria della Misericordia di Udine ( Site 0434)

Udine, 33100, Italy

Location

Aichi Cancer Center Hospital ( Site 0165)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 0178)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center ( Site 0186)

Matsuyama, Ehime, 791-0280, Japan

Location

Hokkaido University Hospital ( Site 0160)

Sapporo, Hokkaido, 060-8648, Japan

Location

Hyogo Cancer Center ( Site 0182)

Akashi, Hyōgo, 673-8558, Japan

Location

Kobe University Hospital ( Site 0188)

Kobe, Hyōgo, 650-0017, Japan

Location

Kobe City Medical Center General Hospital ( Site 0181)

Kobe, Hyōgo, 650-0047, Japan

Location

Ibaraki Prefectural Central Hospital ( Site 0177)

Kasama, Ibaraki, 309-1793, Japan

Location

Iwate Medical University Hospital ( Site 0184)

Shiwa-gun, Iwate, 028-3695, Japan

Location

St. Marianna University School of Medicine Hospital ( Site 0187)

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kanagawa Cancer Center ( Site 0167)

Yokohama, Kanagawa, 241-8515, Japan

Location

Kansai Medical University Hospital ( Site 0190)

Hirakata, Osaka, 573-1191, Japan

Location

Osaka University Hospital ( Site 0162)

Suita, Osaka, 565-0871, Japan

Location

Osaka Medical College Hospital ( Site 0168)

Takatsuki, Osaka, 569-8686, Japan

Location

Saitama Cancer Center ( Site 0170)

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute ( Site 0176)

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Chiba Cancer Center ( Site 0180)

Chiba, 260-8717, Japan

Location

National Hospital Organization Kyushu Cancer Center ( Site 0172)

Fukuoka, 811-1395, Japan

Location

Kyushu University Hospital ( Site 0173)

Fukuoka, 812-8582, Japan

Location

Gifu University Hospital ( Site 0166)

Gifu, 501-1194, Japan

Location

Hiroshima City Hiroshima Citizens Hospital ( Site 0171)

Hiroshima, 730-8518, Japan

Location

Kochi Health Sciences Center ( Site 0189)

Kochi, 781-8555, Japan

Location

Kumamoto University Hospital ( Site 0164)

Kumamoto, 860-8556, Japan

Location

Niigata Cancer Center Hospital ( Site 0169)

Niigata, 951-8566, Japan

Location

Osaka International Cancer Institute ( Site 0161)

Osaka, 541-8567, Japan

Location

Osaka General Medical Center ( Site 0159)

Osaka, 558-8558, Japan

Location

National Cancer Center Hospital ( Site 0179)

Tokyo, 104-0045, Japan

Location

Tokyo Metropolitan Komagome Hospital ( Site 0183)

Tokyo, 113-8677, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 0185)

Tokyo, 135-8550, Japan

Location

Toyama Prefectural Central Hospital ( Site 0163)

Toyama, 930-8550, Japan

Location

Riga East Clinical University Hospital ( Site 0550)

Riga, 1079, Latvia

Location

LSMUL Kauno Klinikos ( Site 0570)

Kaunas, 50161, Lithuania

Location

Nacionalinis Vezio Institutas ( Site 0569)

Vilnius, 08406, Lithuania

Location

Vilniaus Universiteto Ligonine Santaros Klinikos ( Site 0568)

Vilnius, 08460, Lithuania

Location

Hospital Kuala Lumpur ( Site 0146)

Kuala Lumpur, 50586, Malaysia

Location

University Malaya Medical Centre ( Site 0143)

Kuala Lumpur, 59100, Malaysia

Location

St. Luke s Medical Center ( Site 0622)

Quezon City, National Capital Region, 1102, Philippines

Location

Szpital Uniwersytecki w Krakowie ( Site 0352)

Krakow, Lesser Poland Voivodeship, 31-501, Poland

Location

Wojewodzki Szpital Specjalistyczny we Wroclawiu ( Site 0358)

Wroclaw, Lower Silesian Voivodeship, 51-124, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie ( Site 0351)

Lublin, Lublin Voivodeship, 20-080, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0349)

Warsaw, Masovian Voivodeship, 02-034, Poland

Location

Mazowiecki Szpital Onkologiczny ( Site 0363)

Wieliszew, Masovian Voivodeship, 05-135, Poland

Location

Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 0353)

Kościerzyna, Pomeranian Voivodeship, 83-400, Poland

Location

Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 0354)

Bielsko-Biala, Silesian Voivodeship, 43-300, Poland

Location

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 0361)

Gliwice, Silesian Voivodeship, 44-101, Poland

Location

SPZOZ WSS nr 3 w Rybniku ( Site 0357)

Rybnik, Silesian Voivodeship, 44-200, Poland

Location

Kaluga Regional Clinical Oncology Center ( Site 0345)

Kaluga, Kaluzskaja Oblast, 248007, Russia

Location

SBHI Leningrad Regional Clinical Hospital ( Site 0496)

Saint Petersburg, Leningradskaya Oblast', 194291, Russia

Location

National Medical and Surgical Center n.a. N.I.Pirogov ( Site 0338)

Moscow, Moscow, 105203, Russia

Location

Blokhin National Medical Oncology ( Site 0494)

Moscow, Moscow, 115478, Russia

Location

Leningrad Regional Oncology Center ( Site 0335)

Saint Petersburg, Sankt-Peterburg, 188663, Russia

Location

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 0344)

Saint Petersburg, Sankt-Peterburg, 197758, Russia

Location

City clinical oncological dispensary ( Site 0336)

Saint Petersburg, Sankt-Peterburg, 198255, Russia

Location

Tomsk Scientific Research Institute of Oncology ( Site 0337)

Tomsk, Tomsk Oblast, 634028, Russia

Location

National University Hospital ( Site 0095)

Singapore, Central Singapore, 119074, Singapore

Location

National Cancer Centre Singapore ( Site 0097)

Singapore, Central Singapore, 169610, Singapore

Location

Oncocare Cancer Centre ( Site 0096)

Singapore, Central Singapore, 258499, Singapore

Location

Chonnam National University Hwasun Hospital ( Site 0083)

Hwasun Gun, Jeonranamdo, 58128, South Korea

Location

Seoul National University Bundang Hospital ( Site 0085)

Seongnam-si, Kyonggi-do, 13620, South Korea

Location

Kyungpook National University Chilgok Hospital ( Site 0089)

Daegu, Taegu-Kwangyokshi, 41404, South Korea

Location

Gachon University Gil Medical Center ( Site 0087)

Incheon, 21565, South Korea

Location

Korea University Anam Hospital ( Site 0084)

Seoul, 02841, South Korea

Location

Seoul National University Hospital -SNUH- ( Site 0080)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 0081)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 0082)

Seoul, 05505, South Korea

Location

Gangnam Severance Hospital ( Site 0088)

Seoul, 06273, South Korea

Location

SMG-SNU BORAMAE Medical Center ( Site 0086)

Seoul, 07061, South Korea

Location

Taipei Medical University Shuang Ho Hospital ( Site 0068)

New Taipei City, 235, Taiwan

Location

National Cheng Kung University Hospital ( Site 0067)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 0063)

Taipei, 10002, Taiwan

Location

Mackay Memorial Hospital ( Site 0065)

Taipei, 104, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center ( Site 0066)

Taipei, 11259, Taiwan

Location

Chang Gung Medical Foundation. Linkou ( Site 0064)

Taoyuan District, 333, Taiwan

Location

City Clinical Hosp.4 of DCC ( Site 0325)

Dnipro, Dnipropetrovsk Oblast, 49102, Ukraine

Location

MI Kryvyi Rih Oncology Dispensary of Dnipropetrovsk Regional Council ( Site 0589)

Kryviy Rih, Dnipropetrovsk Oblast, 50048, Ukraine

Location

Ivano-Frankivsk Regional Oncology Clinical Dispensary ( Site 0321)

Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018, Ukraine

Location

Communal non profit enterprise Regional Clinical Oncology Center ( Site 0591)

Kharkiv, Kharkivs’ka Oblast’, 61070, Ukraine

Location

National Cancer Institute of the MoH of Ukraine ( Site 0319)

Kyiv, Kyivska Oblast, 03022, Ukraine

Location

Kyiv City Clinical Oncology Center ( Site 0590)

Kyiv, Kyivska Oblast, 03115, Ukraine

Location

University Hospitals Bristol NHS Foundation Trust ( Site 0407)

Bristol, Bristol, City of, BS2 8ED, United Kingdom

Location

Ninewells Hospital and Medical School ( Site 0406)

Dundee, Dundee City, DD1 9SY, United Kingdom

Location

Royal Free London NHS Foundation Trust ( Site 0403)

London, London, City of, NW3 2QG, United Kingdom

Location

The Royal Marsden Foundation Trust ( Site 0405)

London, London, City of, SW3 6JJ, United Kingdom

Location

Imperial College Healthcare NHS Trust ( Site 0402)

London, London, City of, W2 1NY, United Kingdom

Location

Royal Marsden NHS Foundation Trust ( Site 0400)

Sutton, Surrey, SM2 5PT, United Kingdom

Location

The Christie NHS Foundation Trust ( Site 0397)

Manchester, M20 4BX, United Kingdom

Location

Related Publications (4)

• Shitara K, Rha SY, Wyrwicz LS, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Dib Bartolomeo M, Lonardi S, Tabernero J, Van Cutsem E, Janjigian YY, Oh DY, Xu J, Fang X, Shih CS, Bhagia P, Bang YJ; KEYNOTE-585 investigators. Neoadjuvant and adjuvant pembrolizumab plus chemotherapy in locally advanced gastric or gastro-oesophageal cancer (KEYNOTE-585): an interim analysis of the multicentre, double-blind, randomised phase 3 study. Lancet Oncol. 2024 Feb;25(2):212-224. doi: 10.1016/S1470-2045(23)00541-7. Epub 2023 Dec 19.

  PMID: 38134948 RESULT

• Shitara K, Rha SY, Wyrwicz L, Oshima T, Karaseva N, Osipov M, Yasui H, Yabusaki H, Afanasyev S, Park YK, Al-Batran SE, Yoshikawa T, Yanez P, Pietrantonio F, Lonardi S, Fang X, Guan Y, Valderrama A, Leconte P, Bhagia P, Bang YJ; KEYNOTE-585 Investigators. Pembrolizumab Plus Chemotherapy Versus Chemotherapy as Perioperative Therapy in Locally Advanced Gastric and Gastroesophageal Junction Cancer: Final Analysis of the Randomized, Phase III KEYNOTE-585 Study. J Clin Oncol. 2025 Oct 10;43(29):3152-3159. doi: 10.1200/JCO-25-00486. Epub 2025 Aug 19.

  PMID: 40829093 DERIVED

• Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022 May 27;101(21):e29304. doi: 10.1097/MD.0000000000029304.

  PMID: 35623069 DERIVED

• Bang YJ, Van Cutsem E, Fuchs CS, Ohtsu A, Tabernero J, Ilson DH, Hyung WJ, Strong VE, Goetze TO, Yoshikawa T, Tang LH, Hwang PMT, Webb N, Adelberg D, Shitara K. KEYNOTE-585: Phase III study of perioperative chemotherapy with or without pembrolizumab for gastric cancer. Future Oncol. 2019 Mar;15(9):943-952. doi: 10.2217/fon-2018-0581. Epub 2019 Feb 19.

  PMID: 30777447 DERIVED

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Saline Solution; Cisplatin; Capecitabine; Fluorouracil; Docetaxel; Oxaliplatin; Leucovorin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2017
• First Posted: July 18, 2017
• Study Start: October 9, 2017
• Primary Completion: February 16, 2024
• Study Completion: April 23, 2025
• Last Updated: March 9, 2026
• Results First Posted: February 20, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

CA (8); IL (7); LA (1); UA (6); CL (5); US (14); GU (3); IT (7); FR (12); MY (2); ES (1); LI (3); SG (3); PL (9); JP (30); DE (8); GB (7); BR (8); BE (9); RU (8); CN (3); TW (6); KR (10); PH (1)