Study of Pembrolizumab Given With Ipilimumab or Placebo in Participants With Untreated Metastatic Non-Small Cell Lung Cancer (NSCLC) (MK-3475-598/KEYNOTE-598)

A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Plus Ipilimumab vs Pembrolizumab Plus Placebo in Previously Untreated, Stage IV, Metastatic Non-small Cell Lung Cancer Subjects Whose Tumors Are PD-L1 Positive (TPS ≥ 50%) (KEYNOTE-598)

The purpose of this study is to determine the efficacy of pembrolizumab given in combination with either ipilimumab or placebo as first-line treatment in participants with metastatic non-small cell lung cancer (NSCLC). The primary hypothesis of this study is that overall survival (OS) and/or progression-free survival (PFS) is prolonged in participants who receive pembrolizumab and ipilimumab compared to those who receive pembrolizumab and placebo.

With Amendment 6 (effective date: 11-Dec-2020), active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue ipilimumab and placebo and participants who remain on treatment will receive open-label pembrolizumab only.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Biological: Pembrolizumab; Biological: Ipilimumab; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 568
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1118AAT
    • Hospital Aleman ( Site 0208)
  • Cordoba, Argentina, X5016KEH
    • Hospital Privado Centro Medico Cordoba ( Site 0206)
  • La Rioja, Argentina, F5300COE
    • Centro Oncologico Riojano Integral ( Site 0203)
  • Rosario, Argentina, S2000CVB
    • Sanatorio Britanico ( Site 0205)
  • Rosario, Argentina, S2000KZE
    • Instituto de Oncologia de Rosario ( Site 0200)
  • Tucuman, Argentina, T4000IAK
    • Centro Medico San Roque ( Site 0207)
  • Rio Negro
    • Viedma, Rio Negro, Argentina, R8500ACE
      • Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0202)
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DSV
      • Sanatorio Parque ( Site 0201)
• Australia
  • Camperdown, Australia, 2050
    • Chris OBrien Lifehouse ( Site 2100)
  • Douglas, Australia, 4814
    • The Townsville Hospital ( Site 2103)
  • Fitzroy, Australia, 3065
    • St Vincents Hospital Melbourne ( Site 2101)
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Cancer Care Centre ( Site 2102)
  • Western Australia
    • Perth, Western Australia, Australia, 6150
      • Fiona Stanley Hospital ( Site 2105)
• Brazil
  • Barretos, Brazil, 14784-400
    • Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0312)
  • Florianopolis, Brazil, 88034-000
    • CEPON Centro de Pesquisa Oncológicas ( Site 0307)
  • Sao Paulo, Brazil, 04039-004
    • Hospital do Servidor Publico do Estado ( Site 0308)
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50070-550
      • Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0302)
  • RS
    • Porto Alegre, RS, Brazil, 91350-200
      • Hospital Nossa Senhora da Conceicao ( Site 0306)
  • Rio Grande Do Sul
    • Santa Maria, Rio Grande Do Sul, Brazil, 97015-513
      • Clinica de Hematologia e Oncologia Viver Ltda ( Site 0305)
  • SP
    • Sao Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer de Sao Paulo - ICESP ( Site 0300)
    • Sao Paulo, SP, Brazil, 01323-020
      • Hospital Alemao Oswaldo Cruz ( Site 0311)
    • Sao Paulo, SP, Brazil, 04024-002
      • Escola Paulista de Medicina - UNIFESP ( Site 0304)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre ( Site 0119)
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba ( Site 0106)
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 5H6
      • CIUSSS du Saguenay-Lac-St-Jean ( Site 0115)
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • CISSS de la Monteregie-Centre ( Site 0100)
    • Levis, Quebec, Canada, G6V 3Z1
      • CISSS-CA Hotel-Dieu de Levis ( Site 0108)
    • Montreal, Quebec, Canada, H3T 1M5
      • CIUSSS Ouest de l'Ile - St-Mary's Hospital ( Site 0107)
    • St-Jerome, Quebec, Canada, J7Z 5T3
      • St-Jerome Medical Research Inc ( Site 0113)
• Chile
  • Santiago, Chile, 7500006
    • Soc. Prosalud Montes y Orlandi Ltda (Orlandi Oncologia) ( Site 0401)
  • Santiago, Chile, 8330032
    • Pontificia Universidad Catolica de Chile ( Site 0404)
  • Santiago, Chile, 8380455
    • Instituto Nacional del Cancer ( Site 0406)
  • Vina del Mar, Chile, 2520000
    • Hospital Clinico Vina del Mar ( Site 0400)
  • El Maule
    • Talca, El Maule, Chile, 3465584
      • Clinica Universidad Catolica del Maule ( Site 0413)
• Colombia
  • Bogota, Colombia, 110221
    • Centro de Investigacion Clinica del Country ( Site 0500)
  • Bogota, Colombia, 110311
    • Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0506)
  • Monteria, Colombia, 230002
    • Oncomedica S.A. ( Site 0502)
  • Pasto, Colombia, 520001
    • Instituto Cancerologico de Narino Ltda ( Site 0504)
  • Antioquia
    • Medellin, Antioquia, Colombia, 050034
      • Hospital Pablo Tobon Uribe ( Site 0505)
• France
  • Bordeaux, France, 33076
    • Institut Bergonie ( Site 0803)
  • Brest, France, 29200
    • CHU de Brest. Hopital Morvan ( Site 0800)
  • Creteil, France, 94010
    • Centre Hopitalier Intercommunal Creteil ( Site 0802)
  • Le Mans, France, 72037
    • Centre Hospitalier Le Mans ( Site 0804)
  • Lille, France, 59037
    • C.H.R.U de Lille - Hopital Calmette ( Site 0805)
  • Paris, France, 75020
    • Hopital Tenon ( Site 0810)
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil ( Site 0809)
  • Toulouse, France, 31059
    • CHU de Toulouse - Hopital Larrey ( Site 0801)
  • Cedex 20
    • Marseille, Cedex 20, France, 13015
      • Hopital Nord du Marseille ( Site 0808)
• Germany
  • Berlin, Germany, 13125
    • Evangelische Lungenklinik Berlin ( Site 0903)
  • Berlin, Germany, 13585
    • Vivantes Klinikum Spandau ( Site 0910)
  • Berlin, Germany, 14165
    • HELIOS Klinikum Emil von Behring ( Site 0905)
  • Gera, Germany, 07548
    • SRH Waldklinikum Gera GmbH ( Site 0907)
  • Grosshansdorf, Germany, 22927
    • LungenClinic Grosshansdorf GmbH ( Site 0908)
  • Heidelberg, Germany, 69126
    • Universitaetsklinikum Heidelberg ( Site 0900)
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig ( Site 0919)
  • Luebeck, Germany, 23538
    • Universitaetsklinikum Schleswig Holstein. ( Site 0918)
• Hungary
  • Budapest, Hungary, 1121
    • Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1502)
  • Budapest, Hungary, 1122
    • Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1506)
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet ( Site 1509)
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont ( Site 1511)
  • Farkasgyepu, Hungary, 8582
    • Veszprem Megyei Tudogyogyintezet ( Site 1503)
  • Gyor, Hungary, 9024
    • Petz Aladar Megyei Oktato Korhaz ( Site 1505)
  • Gyula, Hungary, 5700
    • Bekes Megyei Pandy Kalman Korhaz. ( Site 1507)
  • Szekesfehervar, Hungary, 8000
    • Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 1504)
  • Szolnok, Hungary, 5000
    • Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1501)
• Ireland
  • Dublin, Ireland, Dublin 8
    • St James Hospital ( Site 1401)
  • Dublin, Ireland, D09 V2N0
    • Beaumont Hospital ( Site 1312)
  • Limerick, Ireland, V94 F858
    • University Hospital Limerick ( Site 1403)
• Italy
  • Brescia, Italy, 25123
    • ASST Spedali Civili ( Site 1001)
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia ( Site 1007)
  • Monza, Italy, 20900
    • Ospedale San Gerardo ASST Monza ( Site 1002)
  • Napoli, Italy, 80131
    • AORN dei Colli Plesso Monaldi ( Site 1003)
  • Perugia, Italy, 06132
    • Ospedale Santa Maria della Misericordia ( Site 1008)
  • Foggia
    • San Giovanni Rotondo (FG), Foggia, Italy, 71013
      • IRCCS Casa Sollievo della Sofferenza ( Site 1009)
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Humanitas Research Hospital ( Site 1004)
  • Verona
    • Legnago, Verona, Italy, 37045
      • Ospedale Mater Salutis ( Site 1005)
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital ( Site 2303)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System ( Site 2300)
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 2302)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center ( Site 2301)
• Latvia
  • Riga, Latvia, 1002
    • Pauls Stradins Clinical University Hospital ( Site 1100)
  • Riga, Latvia, 1079
    • Riga East Clinical University Hospital ( Site 1111)
• Mexico
  • Ciudad de Mexico, Mexico, 03310
    • Grupo Medico Camino SC ( Site 0607)
  • Mexico City, Mexico, 14050
    • Medica Sur S.A.B de C.V. ( Site 0608)
  • Puebla, Mexico, 72530
    • Oncologica de Puebla SA de CV ( Site 0606)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44200
      • Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0603)
  • N.l.
    • Monterrey, N.l., Mexico, 64710
      • Avix Investigacion Clinica S.C. ( Site 0600)
  • Yucatan
    • Merida, Yucatan, Mexico, 97070
      • Medical Care and Research S.A. de C.V. ( Site 0602)
• Peru
  • Arequipa, Peru, 04000
    • Centro Especializado de Enfermedades Neoplasicas SRL-CEEN SRL ( Site 0710)
  • Arequipa, Peru, 04000
    • Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 0704)
  • Lima, Peru, 15036
    • Clinica Internacional Sede San Borja ( Site 0701)
  • Lima, Peru, 15102
    • Hospital Nacional Cayetano Heredia ( Site 0706)
  • Trujillo, Peru, 13007
    • Clinica Peruano Americana S.A. ( Site 0703)
  • Lima
    • La Victoria, Lima, Peru, 15033
      • Hospital Nacional Guillermo Almenara Irigoyen ( Site 0705)
• Poland
  • Brzeziny, Poland, 95-060
    • Powiatowe Centrum Zdrowia w Brzezinach ( Site 1615)
  • Bydgoszcz, Poland, 85-796
    • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1609)
  • Konin, Poland, 62-500
    • Przychodnia Lekarska Komed ( Site 1602)
  • Olsztyn, Poland, 10-357
    • Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc ( Site 1607)
  • Poznan, Poland, 60-693
    • MED-POLONIA Sp. z o.o. ( Site 1605)
  • Warszawa, Poland, 02-781
    • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie ( Site 1600)
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 53-413
      • Dolnoslaskie Centrum Onkologii. ( Site 1616)
  • Zachodniopomorskie
    • Koszalin, Zachodniopomorskie, Poland, 75-581
      • Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 1614)
• South Africa
  • Cape Town, South Africa, 7405
    • Vincent Pallotti Hospital ( Site 1811)
  • Cape Town, South Africa, 8000
    • University of Stellenbosch and Tygerberg Hospital ( Site 1810)
  • Durban, South Africa, 4001
    • Dr G.A. Landers Specialist Oncologist ( Site 1803)
  • Johannesburg, South Africa, 2193
    • Charlotte Maxeke Johannesburg Academic Hospital ( Site 1806)
  • Johannesburg, South Africa, 2196
    • Sandton Oncology Medical Group PTY LTD ( Site 1807)
  • Kraaifontein, South Africa, 7570
    • GVI Oncology Clinical Research Centre ( Site 1802)
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Universitas Annex National Hospital ( Site 1800)
  • Gauteng
    • Alberton, Gauteng, South Africa, 1448
      • Clinton Onclogy Clinic ( Site 1804)
    • Pretoria, Gauteng, South Africa, 0081
      • Wilgers Oncology Centre ( Site 1808)
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d Hebron ( Site 1211)
  • Madrid, Spain, 28040
    • Hospital Fundacion Jimenez Diaz - Clin. Concepcion ( Site 1209)
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio ( Site 1200)
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias i Pujol ( Site 1207)
    • Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Hospital Duran i Reynals ( Site 1201)
  • Extremadura
    • Caceres, Extremadura, Spain, 10003
      • Hospital San Pedro de Alcantara ( Site 1208)
  • Gran Canaria
    • Las Palmas de Gran Canaria, Gran Canaria, Spain, 35001
      • Hospital Universitario Insular de Gran Canaria ( Site 1203)
• Taiwan
  • Changhua, Taiwan, 50006
    • Changhua Christian Hospital ( Site 2406)
  • Kaohsiung, Taiwan, 833
    • Chang Gung Medical Foundation - Kaohsiung ( Site 2404)
  • Taichung, Taiwan, 404
    • China Medical University Hospital ( Site 2403)
  • Tainan, Taiwan, 70457
    • National Cheng Kung University Hospital ( Site 2401)
  • Taipei, Taiwan, 10048
    • National Taiwan University Hospital ( Site 2400)
  • Taipei, Taiwan, 104
    • Mackay Memorial Hospital ( Site 2405)
  • Taoyuan, Taiwan, 33305
    • Chang Gung Memorial Hospital - Linkou Branch ( Site 2402)
• Thailand
  • Bangkok, Thailand, 10330
    • Chulalongkorn Hospital ( Site 2561)
  • Bangkok, Thailand, 10400
    • Pramongkutklao Hospital ( Site 2564)
  • Bangkok, Thailand, 10700
    • Siriraj Hospital ( Site 2562)
  • Khon Kaen, Thailand, 40002
    • Khon Kaen University ( Site 2565)
  • Bangkok
    • Ratchthevee, Bangkok, Thailand, 10400
      • Ramathibodi Hospital. ( Site 2563)
  • Chiang Mai
    • Mueang, Chiang Mai, Thailand, 50000
      • Bangkok Hospital Chiangmai ( Site 2560)
• Turkey
  • Adana, Turkey, 01130
    • Acibadem Adana Hastanesi ( Site 1904)
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1908)
  • Bursa, Turkey, 16059
    • Uludag Universitesi Tip Fakultesi ( Site 1914)
  • Cankaya - Ankara, Turkey, 06490
    • Ankara Sehir Hastanesi ( Site 1903)
  • Edirne, Turkey, 22030
    • Trakya Uni. Tip Fakultesi ( Site 1911)
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1906)
  • Istanbul, Turkey, 34899
    • Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 1912)
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi Hastanesi ( Site 1901)
  • Izmir, Turkey, 35575
    • Medical Park Izmir Hospital ( Site 1900)
  • Kocaeli, Turkey, 41380
    • Kocaeli Universitesi Tip Fakultesi ( Site 1909)
  • Malatya, Turkey, 44280
    • Inonu Universitesi Tip Fakultesi ( Site 1907)
  • Trabzon, Turkey, 61080
    • Karadeniz Teknik Universitesi ( Site 1910)
• Ukraine
  • Cherkasy, Ukraine, 18009
    • Cherkasy Regional Hospital ( Site 2020)
  • Chernivtsy, Ukraine, 58013
    • Regional Clinical Onco Dispensary_ State Medical University ( Site 2012)
  • Dnipropetrovsk, Ukraine, 49102
    • Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC ( Site 2000)
  • Ivano-Frankivsk, Ukraine, 76018
    • MI Prykarpatskyi Clinical Oncology Centrum ( Site 2009)
  • Kropyvnytskyi, Ukraine, 25006
    • PP PPC Acinus Medical and Diagnostic Centre ( Site 2002)
  • Kyiv, Ukraine, 03002
    • National Cancer Institute of the MoH of Ukraine ( Site 2015)
  • Kyiv, Ukraine, 03115
    • Kyiv City Clinical Oncological Center ( Site 2014)
  • Lviv, Ukraine, 79031
    • Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2003)
  • Odesa, Ukraine, 65055
    • MI Odessa Regional Oncological Centre ( Site 2004)
  • Dnipropetrovsk Region
    • Kryviy Rih, Dnipropetrovsk Region, Ukraine, 50048
      • MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2005)
• United Kingdom
  • Belfast, United Kingdom, BT9 7AB
    • Belfast City Hospital ( Site 1302)
  • London, United Kingdom, NW3 2QG
    • Royal Free NHS Foundation Trust ( Site 1324)
  • London, United Kingdom, SW17 0QT
    • St. Georges University Hospital NHS Foundation Trust ( Site 1321)
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust.. ( Site 1327)
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust ( Site 1301)
  • Northwood, United Kingdom, HA6 2RN
    • Mount Vernon Cancer Centre ( Site 1307)
  • Wolverhampton, United Kingdom, WV10 0QP
    • Royal Wolverhampton Hospitals NHS Trust ( Site 1323)
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Royal Cornwall Hospital ( Site 1325)
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust. ( Site 1326)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Cancer Center ( Site 0007)
  • California
    • Burbank, California, United States, 91505
      • Disney Family Cancer Center ( Site 0035)
    • Monterey, California, United States, 93940
      • Pacific Cancer Care ( Site 0001)
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute ( Site 0021)
  • Florida
    • Orlando, Florida, United States, 32804
      • Florida Hospital Cancer Institute ( Site 0009)
  • Kentucky
    • Paducah, Kentucky, United States, 42003
      • Mercy Health-Paducah Medical Oncology and Hematology ( Site 0018)
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists ( Site 0019)
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center ( Site 0025)
    • Burlington, Massachusetts, United States, 01805
      • Lahey Hospital & Medical Center ( Site 0020)
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Medical Center ( Site 0022)
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai ( Site 0034)
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center ( Site 0016)
    • Columbus, Ohio, United States, 43219
      • Mid Ohio Oncology/Hematology Inc. ( Site 0003)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Cancer Institute, Franz Clinic - Eastside ( Site 0031)
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System ( Site 8010)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • University of Tennessee Erlanger Oncology & Hematology ( Site 0026)
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists ( Site 0017)
  • Texas
    • Arlington, Texas, United States, 76014
      • Texas Oncology-Arlington South ( Site 8006)
    • Dallas, Texas, United States, 75203
      • Texas Oncology-Methodist Dallas Cancer Center ( Site 8000)
    • Flower Mound, Texas, United States, 75028
      • Texas Oncology-Flower Mound ( Site 8007)
    • Longview, Texas, United States, 75601
      • Texas Oncology-Longview Cancer Center ( Site 8009)
  • Washington
    • Vancouver, Washington, United States, 98684
      • Northwest Cancer Specialists, P.C. ( Site 8001)
    • Yakima, Washington, United States, 98902
      • Virginia Mason Memorial- North Star Lodge Cancer Center ( Site 0033)
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center ( Site 0004)
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Clinical Cancer Center ( Site 0027)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of Stage IV metastatic non-small cell lung cancer (NSCLC) (American Joint Committee on Cancer version 8)
• Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by investigator
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Has a life expectancy of at least 3 months
• Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
• Female participants of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study therapy
• Female participants of reproductive potential must agree to use contraception starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication

Exclusion Criteria:

• Has received prior systemic chemotherapy/other targeted or biological antineoplastic therapy treatment for their Stage IV metastatic NSCLC
• Has a tumor that harbors an epidermal growth factor receptor (EGFR)-sensitizing (activating) mutation or an anaplastic lymphoma kinase (ALK) translocation
• 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 therapy
• Has received prior therapy with an anti-Programmed Cell Death Receptor 1 (PD-1), anti-Programmed Cell Death Receptor Ligand 1 (anti-PD-L1), or anti- Programmed Cell Death Receptor Ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)
• Has received prior radiotherapy within 2 weeks of start of study therapy or received lung radiation therapy of >30 Gray (Gy) within 6 months of the first dose of study therapy
• Has recovered from all radiation-related toxicities, does not require corticosteroids, and has not had radiation pneumonitis
• Is receiving systemic steroid therapy ≤7 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cancers
• Has known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (i.e., doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study therapy
• Has a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
• Has had an allogeneic tissue/solid organ transplant
• Has received a live vaccine within 30 days prior to the first dose of study therapy
• Has an active infection requiring systemic therapy
• 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
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial
• Is a regular user of any illicit drugs or had a recent history of substance abuse
• Is pregnant or breast feeding or expecting to conceive starting from the first dose of study medication, throughout the study period, and for up to 120 days after the last dose of study medication
• Has severe hypersensitivity to pembrolizumab and/or any of its excipients and/or to ipilimumab and/or any of its excipients
• Has a c-ros oncogene 1 (ROS1) mutation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Ipilimumab; Participants receive 200 mg of pembrolizumab by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus 1 mg/kg of ipilimumab by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.	Biological: Pembrolizumab; Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Other Names: MK-3475; KEYTRUDA®; Biological: Ipilimumab; Administered as an IV infusion every 6 weeks (Q6W); Other Names: YERVOY®
Active Comparator: Pembrolizumab + Placebo; Participants receive 200 mg of pembrolizumab by IV infusion on Day 1 of each 3-week cycle for up to 35 cycles of treatment plus placebo by IV infusion on Day 1 of each 6-week cycle for up to 18 cycles of treatment.	Biological: Pembrolizumab; Administered as an intravenous (IV) infusion every 3 weeks (Q3W); Other Names: MK-3475; KEYTRUDA®; Other: Placebo; Normal saline solution administered as an IV infusion Q6W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. The median survival (in months) and the associated 95% confidence intervals (CIs) were reported using Kaplan-Meier method was used. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) was used to estimate hazard ratio (HR) and 95% CIs for first course study treatment per protocol.	Up to approximately 32 months (through data cut-off date: 01 Sep 2020)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR)	PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in sum of diameters of target lesions. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The median survival (in months) and associated 95% CIs were reported using Kaplan-Meier method. Cox regression model with Efron's method of tie handling with treatment as covariate stratified by ECOG performance status (0 vs. 1), geographic region of the enrolling site (East Asia vs. non-East Asia), and predominant tumor history (squamous vs. non-squamous) was used to estimate HR and 95% CIs for first course study treatment per protocol.	Up to approximately 32 months (through data cut-off date 01 Sep 2020)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR	ORR was defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 by BICR. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. Per protocol the ORR was calculated using the Miettinen & Nurminen method stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and predominant tumor history (squamous versus non-squamous) for the first course of study treatment.	Up to approximately 32 months (data cut-off date 01 Sep 2020)
Duration of Response (DOR) Per RECIST 1.1 Based on BICR	For participants who demonstrated a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. Per protocol, the DOR for all participants who experienced a CR or PR was presented for the first course of study treatment.	Up to approximately 32 months (data cut-off date 01 Sep 2020)
Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath	TTD was defined as the time to the first onset of a 10-point or greater score deterioration from baseline in any one of the 3 symptoms (cough, pain in chest or shortness of breath), confirmed by a second adjacent 10-point or greater score deterioration from baseline. Cough was based on EORTC QLQ-LC13 question 1, pain in chest was based on EORTC QLQ-LC13 question 10, and shortness of breath was based on EORTC QLQ-C30 question 8. Per protocol, TTD was reported for first course study treatment.	Up to approximately 32 months (data cut-off date 01 Sep 2020)
Number of Participants Who Experienced an Adverse Event (AE)	An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who experienced an AE were reported for the first course of study treatment and follow up.	Up to approximately 27 months
Number of Participants Who Discontinued Study Treatment Due to an AE	An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for the first course of study treatment.	Up to approximately 24 months
Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Scale Score to Week 18	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score were presented for first course study treatment.	Baseline, Week 18

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Boyer M, Sendur MAN, Rodriguez-Abreu D, Park K, Lee DH, Cicin I, Yumuk PF, Orlandi FJ, Leal TA, Molinier O, Soparattanapaisarn N, Langleben A, Califano R, Medgyasszay B, Hsia TC, Otterson GA, Xu L, Piperdi B, Samkari A, Reck M; KEYNOTE-598 Investigators. Pembrolizumab Plus Ipilimumab or Placebo for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score >/= 50%: Randomized, Double-Blind Phase III KEYNOTE-598 Study. J Clin Oncol. 2021 Jul 20;39(21):2327-2338. doi: 10.1200/JCO.20.03579. Epub 2021 Jan 29.

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2017
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 7, 2022

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: October 4, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PD-1; PD-L1; PD1; PDL1; Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); CTLA4; Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Ipilimumab
• Other Study ID Numbers: 3475-598; MK-3475-598 (Other Identifier: Merck); KEYNOTE-598 (Other Identifier: Merck); 2016-004364-20 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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