Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)

Stomach Neoplasms Clinical Trial

Official title:

A Phase 3, Randomized, Double-blind Clinical Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-line Treatment in Participants With HER2 Negative, Previously Untreated, Unresectable or Metastatic Gastric Orgastroesophageal Junction Adenocarcinoma (KEYNOTE-859)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03675737
• Other study ID #: 3475-859
• Secondary ID: MK-3475-859KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 8, 2018
• Est. completion date: March 1, 2025

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil [FP regimen] or oxaliplatin combined with capecitabine [CAPOX regimen]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult participants.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1579
• Est. completion date: March 1, 2025
• Est. primary completion date: October 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria

• Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status

• Has human epidermal growth factor receptor 2 (HER2) negative cancer

• Male participants must agree to use contraception during the treatment period and through 95 days after the last dose of chemotherapy, refrain from donating sperm, and be abstinent from heterosexual intercourse, as their preferred and usual lifestyle, and agree to remain abstinent or must agree to use contraception per study protocol unless confirmed to be azoospermic during this period

• Female participants who are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) OR is a WOCBP who agrees to use contraception or be abstinent from heterosexual intercourse, as their preferred and usual lifestyle, during the treatment period and through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last, and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period

• Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator assessment

• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated

• Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis

• Has provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the start of study intervention

• Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Exclusion Criteria

• Has squamous cell or undifferentiated gastric cancer

• Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of the need for major surgery during the course of study intervention, or has not recovered adequately from the toxicity and/or complications from previous surgery

• Has preexisting peripheral neuropathy >Grade 1

• Is a WOCBP who has a positive urine pregnancy test within 24 hours for urine or within 72 hours for serum prior to randomization or treatment allocation

• Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed =6 months prior to randomization

• Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1 or anti-programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX- 40, CD137)

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all adverse events (AEs) due to any previous therapies to =Grade 1 or baseline

• Has received prior radiotherapy within 2 weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease

• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment

• Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy

• Has known active CNS metastases and/or carcinomatous meningitis

• Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients

• Has an active autoimmune disease that has required systemic treatment in past 2 years

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus [HCV] ribonucleic acid [RNA] detected qualitatively) infection

• Has a known history of active tuberculosis

• Has hypokalemia (serum potassium less than the lower limit of normal)

• Has hypomagnesemia (serum magnesium less than the lower limit of normal)

• Has hypocalcemia (serum calcium less than the lower limit of normal)

• Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator

• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last

• Has had an allogenic tissue/solid organ transplant

• Has a known severe hypersensitivity (= Grade 3) to any of the study chemotherapy agents (including, but not limited to, infusional 5-fluorouracil or oral capecitabine) and/or to any of their excipients

• For participants taking cisplatin: has Grade =2 audiometric hearing loss

Related Conditions & MeSH terms

• Adenocarcinoma
• Stomach Neoplasms

Intervention

Biological:
• Pembrolizumab
Administered as an IV infusion on Day 1 Q3W

Drug:
• Cisplatin
Administered as an IV infusion on Day 1 Q3W
• 5-fluorouracil
Administered as a continuous IV infusion on Days 1-5 Q3W
• oxaliplatin
Administered as an IV infusion on Day 1 Q3W
• capecitabine
Administered orally BID on Days 1 to 14 Q3W
• Placebo for Pembrolizumab
Administered as an IV infusion on Day 1 Q3W

Locations

Country	Name	City	State
Argentina	Fundacion Favaloro - Hospital Universitario ( Site 0302)	Buenos Aires
Argentina	Instituto de Investigaciones Metabolicas ( Site 0312)	Buenos Aires
Argentina	Instituto Medico Alexander Fleming ( Site 0307)	Buenos Aires	Caba
Argentina	Centro Oncologico Riojano Integral ( Site 0313)	La Rioja
Argentina	Instituto San Marcos ( Site 0311)	San Juan
Australia	Box Hill Hospital ( Site 2300)	Box Hill	Victoria
Australia	Liverpool Hospital ( Site 2301)	Liverpool	New South Wales
Australia	Southern Medical Day Care Centre ( Site 2303)	Wollongong	New South Wales
Brazil	CIONC - Centro Integrado de Oncologia de Curitiba ( Site 0405)	Curitiba	Parana
Brazil	CEPON - Centro de Pesquisas Oncologicas ( Site 0400)	Florianopolis	Santa Catarina
Brazil	Instituto do Cancer do Ceara ( Site 0407)	Fortaleza	Ceara
Brazil	Hospital de Caridade de Ijui ( Site 0402)	Ijui	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceicao ( Site 0403)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional do Cancer Jose Alencar Gomes da Silva INCA ( Site 0401)	Rio de Janeiro
Brazil	IBCC - Instituto Brasileiro de Controle do Cancer ( Site 0404)	Sao Paulo
Canada	BC Cancer - Abbotsford ( Site 0206)	Abbotsford	British Columbia
Canada	McGill University Health Centre ( Site 0208)	Montreal	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0203)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0202)	Toronto	Ontario
Chile	Fundacion Arturo Lopez Perez FALP ( Site 0501)	Santiago	Region M. De Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 0502)	Santiago	Region M. De Santiago
Chile	Sociedad Oncovida S.A. ( Site 0508)	Santiago	Region M. De Santiago
Chile	Instituto Clinico Oncologico del Sur ( Site 0500)	Temuco	Araucania
China	Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 2425)	Beijing	Beijing
China	The First Hospital of Jilin University ( Site 2416)	Chang chun	Jilin
China	Hunan Cancer Hospital ( Site 2439)	Changsha	Hunan
China	Xiangya Hospital Central-South University ( Site 2419)	Changsha	Hunan
China	Changzhou Cancer Hospital-Changzhou Fourth Peoples Hospital ( Site 2441)	Changzhou	Jiangsu
China	900 Hospital of the Joint ( Site 2418)	Fuzhou	Fujian
China	Fujian Medical University Union Hospital ( Site 2410)	Fuzhou	Fujian
China	Fujian Provincial Cancer Hospital ( Site 2414)	Fuzhou	Fujian
China	Guangdong General Hospital ( Site 2431)	Guangzhou	Guangdong
China	Sir Run Run Show Hospital ( Site 2427)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 2417)	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital ( Site 2446)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 2401)	Harbin	Heilongjiang
China	The First Affiliated Hospital of Nanchang University ( Site 2440)	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital ( Site 2432)	Nanjing	Jiangsu
China	The 81st Hospital of PLA ( Site 2413)	Nanjing	Jiangsu
China	The Affiliated Hospital of Qingdao University ( Site 2405)	Qingdao	Shandong
China	Shanghai East Hospital ( Site 2403)	Shanghai	Shanghai
China	Zhongshan Hospital affiliated to Fudan University ( Site 2407)	Shanghai	Shanghai
China	Peking University Shenzhen Hospital ( Site 2442)	Shenzhen	Guangdong
China	Fourth Hospital Of Hebei Medical University ( Site 2436)	Shijiazhuang	Hebei
China	Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)	Urumqi	Xinjiang
China	Hubei Cancer Hospital ( Site 2434)	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University ( Site 2430)	Xiamen	Fujian
China	Zhongshan Hospital Xiamen University ( Site 2447)	Xiamen	Fujian
China	1st Affil hosp of Med College of Xi'an Jiaotong University ( Site 2428)	XiAn	Shanxi
China	Yancheng First People s Hospital ( Site 2426)	Yancheng	Jiangsu
China	Henan Cancer Hospital ( Site 2415)	Zhengzhou	Henan
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 0605)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 0604)	Cali	Valle Del Cauca
Colombia	Oncomedica S.A. ( Site 0606)	Monteria	Cordoba
Colombia	Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 0608)	Valledupar	Cesar
Costa Rica	CIMCA Centro de Investigacion y Manejo del Cancer ( Site 3001)	San Jose
Costa Rica	ICIMED - Instituto de Investigacion en Ciencias Medicas ( Site 3000)	San Jose
Costa Rica	Policlinico San Bosco ( Site 3002)	San Jose
Czechia	Masarykuv onkologicky ustav ( Site 3103)	Brno	Jihomoravsky Kraj
Czechia	Nemocnice AGEL Novy Jicin a.s. ( Site 3104)	Novy Jicin
Czechia	Fakultni nemocnice Olomouc ( Site 3100)	Olomouc
Czechia	FN Ostrava ( Site 3105)	Ostrava	Moravskoslezsky Kraj
Czechia	Fakultni nemocnice Plzen ( Site 3102)	Plzen	Plzensky Kraj
Czechia	Fakultni Thomayerova nemocnice ( Site 3101)	Praha 4
Denmark	Aalborg University Hospital ( Site 3204)	Aalborg	Nordjylland
Denmark	Rigshospitalet ( Site 3202)	Copenhagen	Hovedstaden
Denmark	Odense Universitets Hospital ( Site 3201)	Odense	Syddanmark
France	CHU-Jean Minjoz ( Site 1002)	Besancon	Doubs
France	C.H.R.U. de Brest - Hopital Morvan ( Site 1007)	Brest	Finistere
France	Centre Oscar Lambret ( Site 1003)	Lille	Nord
France	CHU Hopital Saint Antoine ( Site 1001)	Paris
France	CHU de Rouen ( Site 1006)	Rouen	Ain
France	Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 1004)	Saint-Herblain	Val-de-Marne
France	Institut Gustave Roussy ( Site 1000)	Villejuif	Val-de-Marne
Germany	Charite Universitaetsmedizin Berlin ( Site 1101)	Berlin
Germany	Asklepios Klinik Altona ( Site 1100)	Hamburg
Germany	Facharztzentrum Eppendorf ( Site 1121)	Hamburg
Germany	SLK-Kliniken Heilbronn ( Site 1104)	Heilbronn	Baden-Wurttemberg
Germany	Universitaetsklinikum Leipzig ( Site 1114)	Leipzig	Sachsen
Guatemala	Celan SA ( Site 0705)	Guatemala
Guatemala	Grupo Angeles SA ( Site 0701)	Guatemala
Guatemala	MEDI-K CAYALA ( Site 0704)	Guatemala
Guatemala	Oncomedica ( Site 0702)	Guatemala
Guatemala	Centro Regional de Sub Especialidades Medicas SA ( Site 0703)	Quetzaltenango
Hong Kong	Prince of Wales Hospital ( Site 2503)	Hong Kong
Hong Kong	Princess Margaret Hospital. ( Site 2502)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 2501)	Hong Kong
Hungary	Orszagos Onkologiai Intezet ( Site 3303)	Budapest
Hungary	Semmelweis Egyetem.. ( Site 3305)	Budapest
Hungary	University of Debrecen Medical Center Clinic of Oncology ( Site 3300)	Debrecen
Hungary	Bacs-Kiskun Megyei Korhaz ( Site 3306)	Kecskemet	Bacs-Kiskun
Hungary	Jasz-Nagykun-Szolnok Megyei Hetenyi Gyula Korhaz-Rendelointezet ( Site 3302)	Szolnok	Jasz-Nagykun-Szolnok
Ireland	Beaumont Hospital ( Site 2101)	Dublin
Ireland	St. James s Hospital ( Site 1200)	Dublin
Ireland	Tallaght University Hospital ( Site 1202)	Dublin
Israel	Soroka University Medical Center ( Site 1305)	Beer Sheva
Israel	Rambam Medical Center ( Site 1303)	Haifa
Israel	Edith Wolfson Medical Center ( Site 1307)	Holon	Tell Abib
Israel	Hadassah Ein Karem Jerusalem ( Site 1301)	Jerusalem	Yerushalayim
Israel	Meir Medical Center ( Site 1308)	Kfar Saba
Israel	Rabin Medical Center ( Site 1302)	Petah Tikva
Israel	Chaim Sheba Medical Center ( Site 1304)	Ramat Gan	Tel Aviv
Israel	Sourasky Medical Center ( Site 1306)	Tel Aviv	Tell Abib
Italy	Istituto Europeo di Oncologia ( Site 1411)	Milano	Lombardia
Italy	Istituto Nazionale dei Tumori Fondazione IRCSS ( Site 1402)	Milano
Italy	Istituto Oncologico Veneto ( Site 1412)	Padova
Italy	Azienda Ospedaliera San Camillo Forlanini ( Site 1413)	Roma
Japan	Hyogo Cancer Center ( Site 2604)	Akashi	Hyogo
Japan	National Hospital Organization Kyushu Cancer Center ( Site 2612)	Fukuoka
Japan	Kansai Medical University Hospital ( Site 2608)	Hirakata	Osaka
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 2611)	Hiroshima
Japan	Ibaraki Prefectural Central Hospital ( Site 2610)	Kasama	Ibaraki
Japan	National Cancer Center Hospital East ( Site 2617)	Kashiwa	Chiba
Japan	Kagawa University Hospital ( Site 2615)	Kita-gun	Kagawa
Japan	Saitama Cancer Center ( Site 2601)	Kitaadachi-gun	Saitama
Japan	Kobe City Medical Center General Hospital ( Site 2603)	Kobe	Hyogo
Japan	Kumamoto University Hospital ( Site 2602)	Kumamoto
Japan	Aichi Cancer Center Hospital ( Site 2619)	Nagoya	Aichi
Japan	Niigata Cancer Center Hospital ( Site 2613)	Niigata
Japan	Osaka International Cancer Institute ( Site 2607)	Osaka
Japan	Kindai University Hospital ( Site 2616)	Osakasayama	Osaka
Japan	Kitasato University Hospital ( Site 2618)	Sagamihara	Kanagawa
Japan	Osaka University Hospital ( Site 2600)	Suita	Osaka
Japan	National Cancer Center Hospital ( Site 2606)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 2609)	Tokyo
Japan	Tokyo Metropolitan Komagome Hospital ( Site 2605)	Tokyo
Japan	Kanagawa Cancer Center ( Site 2614)	Yokohama	Kanagawa
Korea, Republic of	Asan Medical Center ( Site 2802)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 2801)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2803)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2800)	Seoul
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran ( Site 0806)	Ciudad de Mexico
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0808)	Guadalajara	Jalisco
Mexico	Medical Care and Research S.A. de C.V. ( Site 0809)	Merida
Mexico	Instituto Nacional de Cancerologia. ( Site 0804)	Mexico City
Mexico	Christus Muguerza Clinica Vidriera ( Site 0802)	Monterrey	Nuevo Leon
New Zealand	Auckland City Hospital ( Site 2700)	Auckland	Northland
Peru	Clinica Ricardo Palma Instituto de Oncologia y Radioterapia ( Site 0908)	Lima
Peru	Clinica San Gabriel ( Site 0907)	Lima
Peru	Hospital Nacional Arzobispo Loayza ( Site 0902)	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 0901)	Lima
Poland	Regionalny Szpital Specjalistyczny im Wl. Bieganskiego w Grudziadzu ( Site 1505)	Grudziadz
Poland	Przychodnia Lekarska Komed ( Site 1514)	Konin	Wielkopolskie
Poland	Szpital Uniwersytecki w Krakowie ( Site 1503)	Krakow	Malopolskie
Poland	Magodent Szpital Elblaska ( Site 1509)	Warszawa	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii we Wroclawiu ( Site 1504)	Wroclaw	Dolnoslaskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego ( Site 1506)	Wroclaw	Dolnoslaskie
Russian Federation	Chelyabinsk Regional Clinical Oncology Dispensary-Chemotherapy ( Site 1608)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Blokhin National Medical Oncology ( Site 1604)	Moscow	Moskva
Russian Federation	Central Clinical Hospital with Polyclinic ( Site 1614)	Moscow	Moskva
Russian Federation	City Clinical Oncology Center ( Site 1603)	Saint Petersburg	Sankt-Peterburg
Russian Federation	SBHI Leningrad Regional Clinical Hospital ( Site 1616)	Saint Petersburg	Leningradskaya Oblast
Russian Federation	SBHI Samara Regional Clinical Oncology Dispensary ( Site 1609)	Samara	Samarskaya Oblast
South Africa	Universitas Annex National Hospital ( Site 1701)	Bloemfontein	Free State
South Africa	Cancercare Rondebosch Oncology ( Site 1709)	Cape Town	Western Cape
South Africa	Groote Schuur Hospital ( Site 1706)	Cape Town	Western Cape
South Africa	The Oncology Centre Overport and Umhlanga ( Site 1705)	Durban	Kwazulu-Natal
South Africa	Outeniqua Cancercare Oncology Unit ( Site 1704)	George	Western Cape
South Africa	Sandton Oncology Medical Group PTY LTD ( Site 1700)	Johannesburg	Gauteng
South Africa	Cape Town Oncology Trials Pty Ltd ( Site 1703)	Kraaifontein	Western Cape
South Africa	Wits Clinical Research ( Site 1707)	Parktown-Johannesburg	Gauteng
South Africa	Cancer Care Langenhoven Drive Oncology Centre ( Site 1708)	Port Elizabeth	Eastern Cape
South Africa	Tshwane District Hospital ( Site 1702)	Pretoria	Gauteng
Spain	Institut Catala d Oncologia Hospital Germans Trias i Pujol ( Site 1806)	Badalona	Barcelona
Spain	Hospital General Universitari Vall d Hebron ( Site 1801)	Barcelona
Spain	Hospital General Universitario de Elche ( Site 1803)	Elche	Alicante
Spain	Hospital Universitario General de Asturias ( Site 1802)	Oviedo	Asturias
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1805)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Marques de Valdecilla ( Site 1804)	Santander	Cantabria
Switzerland	Universitaetsspital Basel ( Site 1900)	Basel	Basel-Stadt
Switzerland	Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1905)	Bellinzona	Ticino
Switzerland	Kantonsspital Graubuenden ( Site 1903)	Chur	Grisons
Switzerland	Hopitaux Universitaires de Geneve HUG ( Site 1907)	Geneva	Geneve
Switzerland	Luzern Kantonsspital ( Site 1904)	Luzern
Switzerland	Kantonsspital St. Gallen ( Site 1901)	St. Gallen	Sankt Gallen
Switzerland	Universitaetsspital Zuerich ( Site 1902)	Zuerich	Zurich
Taiwan	Chang Gung Medical Foundation. Kaohsiung Branch ( Site 2902)	Kaohsiung
Taiwan	National Cheng Kung University Hospital ( Site 2901)	Tainan
Taiwan	Mackay Memorial Hospital ( Site 2903)	Taipei
Taiwan	National Taiwan University Hospital ( Site 2900)	Taipei
Turkey	Adana Sehir Hastanesi ( Site 2002)	Adana
Turkey	Abdurrahman Yurtaslan Onkoloji Egitim ve Arastirma Hastanesi ( Site 2006)	Ankara
Turkey	Hacettepe University Medical Faculty ( Site 2017)	Ankara
Turkey	Trakya Universitesi Tip Fakultesi ( Site 2015)	Edirne
Turkey	Ataturk Universitesi Tip Fakultesi Hastanesi ( Site 2000)	Erzurum
Turkey	Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 2001)	Istanbul
Turkey	Dokuz Eylul Universitesi Tip Fakultesi Hastanesi ( Site 2011)	Izmir
Turkey	Malatya Inonu Universitesi Tip Fakultesi Hastanesi ( Site 2009)	Malatya
Turkey	Sakarya Universitesi Egitim ve Arastirma Hastanesi ( Site 2012)	Sakarya
Ukraine	City Clinical Hosp.4 of DCC ( Site 2201)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 2204)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 2208)	Kharkiv	Kharkivska Oblast
Ukraine	MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2200)	Kryviy Rih	Dnipropetrovska Oblast
Ukraine	Clinic of National Cancer Institute ( Site 2203)	Kyiv	Kyivska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 2213)	Kyiv
Ukraine	Medical and Diagnostic Centre LLC Dobryi Prognoz ( Site 2205)	Kyiv	Kyivska Oblast
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2210)	Lviv	Lvivska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 2212)	Odesa	Odeska Oblast
Ukraine	Medical Centre LLC Oncolife ( Site 2202)	Zaporizhzhya	Zaporizka Oblast
United Kingdom	Castle Hill Hospital ( Site 1201)	Cottingham	East Riding Of Yorkshire
United Kingdom	St. Georges University Hospital NHS Foundation Trust ( Site 1204)	London	London, City Of
United Kingdom	University College London Hospital ( Site 1211)	London	London, City Of
United Kingdom	South Devon Healthcare Foundation Trust. Torbay Hospital ( Site 1205)	Torquay	Devon
United States	Greater Baltimore Medical Center ( Site 0102)	Baltimore	Maryland
United States	UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0124)	Los Angeles	California
United States	University of Miami, Sylvester Comprehensive Cancer Center ( Site 0113)	Miami	Florida
United States	Minnesota Oncology Hematology, PA ( Site 8000)	Minneapolis	Minnesota
United States	UC Irvine Health/Division of Hematology Oncology, Dept of Medicine ( Site 0128)	Orange	California
United States	Cancer Treatment Centers of America - Philadelphia ( Site 0112)	Philadelphia	Pennsylvania
United States	Allegheny General Hospital ( Site 0118)	Pittsburgh	Pennsylvania
United States	Oncology & Hematology Assoc. SW Virginia, Inc., DBA Blue Ridge Cancer Care ( Site 8001)	Roanoke	Virginia
United States	University of Rochester ( Site 0122)	Rochester	New York
United States	Wenatchee Valley Clinic [Wenatchee, WA] ( Site 0116)	Wenatchee	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  China,  Colombia,  Costa Rica,  Czechia,  Denmark,  France,  Germany,  Guatemala,  Hong Kong,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  New Zealand,  Peru,  Poland,  Russian Federation,  South Africa,  Spain,  Switzerland,  Taiwan,  Turkey,  Ukraine,  United Kingdom, 

References & Publications (1)

Rha SY, Oh DY, Yanez P, Bai Y, Ryu MH, Lee J, Rivera F, Alves GV, Garrido M, Shiu KK, Fernandez MG, Li J, Lowery MA, Cil T, Cruz FM, Qin S, Luo S, Pan H, Wainberg ZA, Yin L, Bordia S, Bhagia P, Wyrwicz LS; KEYNOTE-859 investigators. Pembrolizumab plus che — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS) in All Participants	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. OS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 45.9 months
Primary	Overall Survival (OS) In Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. OS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 45.9 months
Primary	Overall Survival (OS) In Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =10	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. OS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 45.9 months
Secondary	Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in All Participants	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1 as assessed by BICR, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. PFS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1 as assessed by BICR, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. PFS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =10	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1 as assessed by BICR, PD was defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. PFS was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in All Participants	ORR was defined as the percentage of the participants who had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 as assessed by BICR.	Up to 49.5 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1	ORR was defined as the percentage of the participants who had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 as assessed by BICR.	Up to 49.5 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =10	ORR was defined as the percentage of the participants who had a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD) according to RECIST 1.1 as assessed by BICR.	Up to 49.5 months
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in All Participants	DOR was defined as the time from first documented evidence of a confirmed Complete Response (CR) or Partial Response (PR) until progressive disease (PD) or death, whichever occurred first. Per RECIST 1.1 as assessed by BICR, CR was the disappearance of all target lesions and PR was =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. PD was defined as =20% increase in the SOD of target lesions according to RECIST 1.1. In addition to the relative increase of 20%, the SOD must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. DOR for participants who had not progressed or died at the time of analysis was censored at the date of the last tumor assessment. DOR was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =1	DOR was defined as the time from first documented evidence of a confirmed Complete Response (CR) or Partial Response (PR) until progressive disease (PD) or death, whichever occurred first. Per RECIST 1.1 as assessed by BICR, CR was the disappearance of all target lesions and PR was =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. PD was defined as =20% increase in the SOD of target lesions according to RECIST 1.1. In addition to the relative increase of 20%, the SOD must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. DOR for participants who had not progressed or died at the time of analysis was censored at the date of the last tumor assessment. DOR was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Blinded Independent Central Review (BICR) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) =10	DOR was defined as the time from first documented evidence of a confirmed Complete Response (CR) or Partial Response (PR) until progressive disease (PD) or death, whichever occurred first. Per RECIST 1.1 as assessed by BICR, CR was the disappearance of all target lesions and PR was =30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. PD was defined as =20% increase in the SOD of target lesions according to RECIST 1.1. In addition to the relative increase of 20%, the SOD must also have demonstrated an absolute increase of =5 mm. The appearance of =1 new lesions was also considered PD. DOR for participants who had not progressed or died at the time of analysis was censored at the date of the last tumor assessment. DOR was estimated using the product-limit (Kaplan-Meier) method for censored data.	Up to 49.5 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE was defined as any untoward medical occurrence, in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE is presented.	Up to 36.7 months
Secondary	Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE is presented.	Up to 33.7 months

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