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

• ClinicalTrials.gov Identifier: NCT03302234
• Recruitment Status: Completed
• First Posted: October 5, 2017
• Results First Posted: September 10, 2021
• Last Update Posted: October 4, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Non-Small-Cell Lung	Biological: Pembrolizumab; Biological: Ipilimumab; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 568 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: December 14, 2017
• Actual Primary Completion Date: September 1, 2020
• Actual Study Completion Date: September 7, 2022

Arms and Interventions

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: KEYTRUDA®; MK-3475; Biological: Ipilimumab; Administered as an IV infusion every 6 weeks (Q6W); Other Name: 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: KEYTRUDA®; MK-3475; Other: Placebo; Normal saline solution administered as an IV infusion Q6W

Outcome Measures

Primary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Up to approximately 32 months (through data cut-off date: 01 Sep 2020) ]
   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.
2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 32 months (through data cut-off date 01 Sep 2020) ]
   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.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) Per RECIST 1.1 Based on BICR [ Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020) ]
   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.
2. Duration of Response (DOR) Per RECIST 1.1 Based on BICR [ Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020) ]
   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.
3. Time to True Deterioration (TTD) in Cough, Pain in Chest, and Shortness of Breath [ Time Frame: Up to approximately 32 months (data cut-off date 01 Sep 2020) ]
   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.
4. Number of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 27 months ]
   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.
5. Number of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to approximately 24 months ]
   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.
6. 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 [ Time Frame: Baseline, 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic Cancer Center ( Site 0007)

Phoenix, Arizona, United States, 85054

United States, California

Disney Family Cancer Center ( Site 0035)

Burbank, California, United States, 91505

Pacific Cancer Care ( Site 0001)

Monterey, California, United States, 93940

John Wayne Cancer Institute ( Site 0021)

Santa Monica, California, United States, 90404

United States, Florida

Florida Hospital Cancer Institute ( Site 0009)

Orlando, Florida, United States, 32804

United States, Kentucky

Mercy Health-Paducah Medical Oncology and Hematology ( Site 0018)

Paducah, Kentucky, United States, 42003

United States, Maine

New England Cancer Specialists ( Site 0019)

Scarborough, Maine, United States, 04074

United States, Massachusetts

Boston Medical Center ( Site 0025)

Boston, Massachusetts, United States, 02118

Lahey Hospital & Medical Center ( Site 0020)

Burlington, Massachusetts, United States, 01805

United States, New Jersey

Holy Name Medical Center ( Site 0022)

Teaneck, New Jersey, United States, 07666

United States, New York

Icahn School of Medicine at Mount Sinai ( Site 0034)

New York, New York, United States, 10029

United States, Ohio

The Ohio State University Wexner Medical Center ( Site 0016)

Columbus, Ohio, United States, 43210

Mid Ohio Oncology/Hematology Inc. ( Site 0003)

Columbus, Ohio, United States, 43219

United States, Oregon

Providence Cancer Institute, Franz Clinic - Eastside ( Site 0031)

Portland, Oregon, United States, 97213

United States, South Carolina

Greenville Health System ( Site 8010)

Greenville, South Carolina, United States, 29615

United States, Tennessee

University of Tennessee Erlanger Oncology & Hematology ( Site 0026)

Chattanooga, Tennessee, United States, 37403

Tennessee Cancer Specialists ( Site 0017)

Knoxville, Tennessee, United States, 37909

United States, Texas

Texas Oncology-Arlington South ( Site 8006)

Arlington, Texas, United States, 76014

Texas Oncology-Methodist Dallas Cancer Center ( Site 8000)

Dallas, Texas, United States, 75203

Texas Oncology-Flower Mound ( Site 8007)

Flower Mound, Texas, United States, 75028

Texas Oncology-Longview Cancer Center ( Site 8009)

Longview, Texas, United States, 75601

United States, Washington

Northwest Cancer Specialists, P.C. ( Site 8001)

Vancouver, Washington, United States, 98684

Virginia Mason Memorial- North Star Lodge Cancer Center ( Site 0033)

Yakima, Washington, United States, 98902

United States, Wisconsin

University of Wisconsin Carbone Cancer Center ( Site 0004)

Madison, Wisconsin, United States, 53792

Medical College of Wisconsin Clinical Cancer Center ( Site 0027)

Milwaukee, Wisconsin, United States, 53226

Argentina

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0202)

Viedma, Rio Negro, Argentina, R8500ACE

Sanatorio Parque ( Site 0201)

Rosario, Santa Fe, Argentina, S2000DSV

Hospital Aleman ( Site 0208)

Buenos Aires, Argentina, C1118AAT

Hospital Privado Centro Medico Cordoba ( Site 0206)

Cordoba, Argentina, X5016KEH

Centro Oncologico Riojano Integral ( Site 0203)

La Rioja, Argentina, F5300COE

Sanatorio Britanico ( Site 0205)

Rosario, Argentina, S2000CVB

Instituto de Oncologia de Rosario ( Site 0200)

Rosario, Argentina, S2000KZE

Centro Medico San Roque ( Site 0207)

Tucuman, Argentina, T4000IAK

Australia, Queensland

Mater Cancer Care Centre ( Site 2102)

South Brisbane, Queensland, Australia, 4101

Australia, Western Australia

Fiona Stanley Hospital ( Site 2105)

Perth, Western Australia, Australia, 6150

Australia

Chris OBrien Lifehouse ( Site 2100)

Camperdown, Australia, 2050

The Townsville Hospital ( Site 2103)

Douglas, Australia, 4814

St Vincents Hospital Melbourne ( Site 2101)

Fitzroy, Australia, 3065

Brazil

Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0302)

Recife, Pernambuco, Brazil, 50070-550

Clinica de Hematologia e Oncologia Viver Ltda ( Site 0305)

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

Hospital Nossa Senhora da Conceicao ( Site 0306)

Porto Alegre, RS, Brazil, 91350-200

Instituto do Cancer de Sao Paulo - ICESP ( Site 0300)

Sao Paulo, SP, Brazil, 01246-000

Hospital Alemao Oswaldo Cruz ( Site 0311)

Sao Paulo, SP, Brazil, 01323-020

Escola Paulista de Medicina - UNIFESP ( Site 0304)

Sao Paulo, SP, Brazil, 04024-002

Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0312)

Barretos, Brazil, 14784-400

CEPON Centro de Pesquisa Oncológicas ( Site 0307)

Florianopolis, Brazil, 88034-000

Hospital do Servidor Publico do Estado ( Site 0308)

Sao Paulo, Brazil, 04039-004

Canada, Alberta

Tom Baker Cancer Centre ( Site 0119)

Calgary, Alberta, Canada, T2N 4N2

Canada, Manitoba

CancerCare Manitoba ( Site 0106)

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Quebec

CIUSSS du Saguenay-Lac-St-Jean ( Site 0115)

Chicoutimi, Quebec, Canada, G7H 5H6

CISSS de la Monteregie-Centre ( Site 0100)

Greenfield Park, Quebec, Canada, J4V 2H1

CISSS-CA Hotel-Dieu de Levis ( Site 0108)

Levis, Quebec, Canada, G6V 3Z1

CIUSSS Ouest de l'Ile - St-Mary's Hospital ( Site 0107)

Montreal, Quebec, Canada, H3T 1M5

St-Jerome Medical Research Inc ( Site 0113)

St-Jerome, Quebec, Canada, J7Z 5T3

Chile

Clinica Universidad Catolica del Maule ( Site 0413)

Talca, El Maule, Chile, 3465584

Soc. Prosalud Montes y Orlandi Ltda (Orlandi Oncologia) ( Site 0401)

Santiago, Chile, 7500006

Pontificia Universidad Catolica de Chile ( Site 0404)

Santiago, Chile, 8330032

Instituto Nacional del Cancer ( Site 0406)

Santiago, Chile, 8380455

Hospital Clinico Vina del Mar ( Site 0400)

Vina del Mar, Chile, 2520000

Colombia

Hospital Pablo Tobon Uribe ( Site 0505)

Medellin, Antioquia, Colombia, 050034

Centro de Investigacion Clinica del Country ( Site 0500)

Bogota, Colombia, 110221

Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0506)

Bogota, Colombia, 110311

Oncomedica S.A. ( Site 0502)

Monteria, Colombia, 230002

Instituto Cancerologico de Narino Ltda ( Site 0504)

Pasto, Colombia, 520001

France

Hopital Nord du Marseille ( Site 0808)

Marseille, Cedex 20, France, 13015

Institut Bergonie ( Site 0803)

Bordeaux, France, 33076

CHU de Brest. Hopital Morvan ( Site 0800)

Brest, France, 29200

Centre Hopitalier Intercommunal Creteil ( Site 0802)

Creteil, France, 94010

Centre Hospitalier Le Mans ( Site 0804)

Le Mans, France, 72037

C.H.R.U de Lille - Hopital Calmette ( Site 0805)

Lille, France, 59037

Hopital Tenon ( Site 0810)

Paris, France, 75020

Nouvel Hopital Civil ( Site 0809)

Strasbourg, France, 67091

CHU de Toulouse - Hopital Larrey ( Site 0801)

Toulouse, France, 31059

Germany

Evangelische Lungenklinik Berlin ( Site 0903)

Berlin, Germany, 13125

Vivantes Klinikum Spandau ( Site 0910)

Berlin, Germany, 13585

HELIOS Klinikum Emil von Behring ( Site 0905)

Berlin, Germany, 14165

SRH Waldklinikum Gera GmbH ( Site 0907)

Gera, Germany, 07548

LungenClinic Grosshansdorf GmbH ( Site 0908)

Grosshansdorf, Germany, 22927

Universitaetsklinikum Heidelberg ( Site 0900)

Heidelberg, Germany, 69126

Universitaetsklinikum Leipzig ( Site 0919)

Leipzig, Germany, 04103

Universitaetsklinikum Schleswig Holstein. ( Site 0918)

Luebeck, Germany, 23538

Hungary

Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1502)

Budapest, Hungary, 1121

Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1506)

Budapest, Hungary, 1122

Orszagos Onkologiai Intezet ( Site 1509)

Budapest, Hungary, 1122

Debreceni Egyetem Klinikai Kozpont ( Site 1511)

Debrecen, Hungary, 4032

Veszprem Megyei Tudogyogyintezet ( Site 1503)

Farkasgyepu, Hungary, 8582

Petz Aladar Megyei Oktato Korhaz ( Site 1505)

Gyor, Hungary, 9024

Bekes Megyei Pandy Kalman Korhaz. ( Site 1507)

Gyula, Hungary, 5700

Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 1504)

Szekesfehervar, Hungary, 8000

Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1501)

Szolnok, Hungary, 5000

Ireland

Beaumont Hospital ( Site 1312)

Dublin, Ireland, D09 V2N0

St James Hospital ( Site 1401)

Dublin, Ireland, Dublin 8

University Hospital Limerick ( Site 1403)

Limerick, Ireland, V94 F858

Italy

IRCCS Casa Sollievo della Sofferenza ( Site 1009)

San Giovanni Rotondo (FG), Foggia, Italy, 71013

Humanitas Research Hospital ( Site 1004)

Rozzano, Milano, Italy, 20089

Ospedale Mater Salutis ( Site 1005)

Legnago, Verona, Italy, 37045

ASST Spedali Civili ( Site 1001)

Brescia, Italy, 25123

Istituto Europeo di Oncologia ( Site 1007)

Milano, Italy, 20141

Ospedale San Gerardo ASST Monza ( Site 1002)

Monza, Italy, 20900

AORN dei Colli Plesso Monaldi ( Site 1003)

Napoli, Italy, 80131

Ospedale Santa Maria della Misericordia ( Site 1008)

Perugia, Italy, 06132

Korea, Republic of

Seoul National University Hospital ( Site 2303)

Seoul, Korea, Republic of, 03080

Severance Hospital Yonsei University Health System ( Site 2300)

Seoul, Korea, Republic of, 03722

Asan Medical Center ( Site 2302)

Seoul, Korea, Republic of, 05505

Samsung Medical Center ( Site 2301)

Seoul, Korea, Republic of, 06351

Latvia

Pauls Stradins Clinical University Hospital ( Site 1100)

Riga, Latvia, 1002

Riga East Clinical University Hospital ( Site 1111)

Riga, Latvia, 1079

Mexico

Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0603)

Guadalajara, Jalisco, Mexico, 44200

Avix Investigacion Clinica S.C. ( Site 0600)

Monterrey, N.l., Mexico, 64710

Medical Care and Research S.A. de C.V. ( Site 0602)

Merida, Yucatan, Mexico, 97070

Grupo Medico Camino SC ( Site 0607)

Ciudad de Mexico, Mexico, 03310

Medica Sur S.A.B de C.V. ( Site 0608)

Mexico City, Mexico, 14050

Oncologica de Puebla SA de CV ( Site 0606)

Puebla, Mexico, 72530

Peru

Hospital Nacional Guillermo Almenara Irigoyen ( Site 0705)

La Victoria, Lima, Peru, 15033

Centro Especializado de Enfermedades Neoplasicas SRL-CEEN SRL ( Site 0710)

Arequipa, Peru, 04000

Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 0704)

Arequipa, Peru, 04000

Clinica Internacional Sede San Borja ( Site 0701)

Lima, Peru, 15036

Hospital Nacional Cayetano Heredia ( Site 0706)

Lima, Peru, 15102

Clinica Peruano Americana S.A. ( Site 0703)

Trujillo, Peru, 13007

Poland

Dolnoslaskie Centrum Onkologii. ( Site 1616)

Wroclaw, Dolnoslaskie, Poland, 53-413

Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 1614)

Koszalin, Zachodniopomorskie, Poland, 75-581

Powiatowe Centrum Zdrowia w Brzezinach ( Site 1615)

Brzeziny, Poland, 95-060

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1609)

Bydgoszcz, Poland, 85-796

Przychodnia Lekarska Komed ( Site 1602)

Konin, Poland, 62-500

Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc ( Site 1607)

Olsztyn, Poland, 10-357

MED-POLONIA Sp. z o.o. ( Site 1605)

Poznan, Poland, 60-693

Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie ( Site 1600)

Warszawa, Poland, 02-781

South Africa

Universitas Annex National Hospital ( Site 1800)

Bloemfontein, Free State, South Africa, 9301

Clinton Onclogy Clinic ( Site 1804)

Alberton, Gauteng, South Africa, 1448

Wilgers Oncology Centre ( Site 1808)

Pretoria, Gauteng, South Africa, 0081

Vincent Pallotti Hospital ( Site 1811)

Cape Town, South Africa, 7405

University of Stellenbosch and Tygerberg Hospital ( Site 1810)

Cape Town, South Africa, 8000

Dr G.A. Landers Specialist Oncologist ( Site 1803)

Durban, South Africa, 4001

Charlotte Maxeke Johannesburg Academic Hospital ( Site 1806)

Johannesburg, South Africa, 2193

Sandton Oncology Medical Group PTY LTD ( Site 1807)

Johannesburg, South Africa, 2196

GVI Oncology Clinical Research Centre ( Site 1802)

Kraaifontein, South Africa, 7570

Spain

Hospital Germans Trias i Pujol ( Site 1207)

Badalona, Barcelona, Spain, 08916

Hospital Duran i Reynals ( Site 1201)

Hospitalet de Llobregat, Barcelona, Spain, 08908

Hospital San Pedro de Alcantara ( Site 1208)

Caceres, Extremadura, Spain, 10003

Hospital Universitario Insular de Gran Canaria ( Site 1203)

Las Palmas de Gran Canaria, Gran Canaria, Spain, 35001

Hospital Universitari Vall d Hebron ( Site 1211)

Barcelona, Spain, 08035

Hospital Fundacion Jimenez Diaz - Clin. Concepcion ( Site 1209)

Madrid, Spain, 28040

Hospital Universitario Virgen del Rocio ( Site 1200)

Sevilla, Spain, 41013

Taiwan

Changhua Christian Hospital ( Site 2406)

Changhua, Taiwan, 50006

Chang Gung Medical Foundation - Kaohsiung ( Site 2404)

Kaohsiung, Taiwan, 833

China Medical University Hospital ( Site 2403)

Taichung, Taiwan, 404

National Cheng Kung University Hospital ( Site 2401)

Tainan, Taiwan, 70457

National Taiwan University Hospital ( Site 2400)

Taipei, Taiwan, 10048

Mackay Memorial Hospital ( Site 2405)

Taipei, Taiwan, 104

Chang Gung Memorial Hospital - Linkou Branch ( Site 2402)

Taoyuan, Taiwan, 33305

Thailand

Ramathibodi Hospital. ( Site 2563)

Ratchthevee, Bangkok, Thailand, 10400

Bangkok Hospital Chiangmai ( Site 2560)

Mueang, Chiang Mai, Thailand, 50000

Chulalongkorn Hospital ( Site 2561)

Bangkok, Thailand, 10330

Pramongkutklao Hospital ( Site 2564)

Bangkok, Thailand, 10400

Siriraj Hospital ( Site 2562)

Bangkok, Thailand, 10700

Khon Kaen University ( Site 2565)

Khon Kaen, Thailand, 40002

Turkey

Acibadem Adana Hastanesi ( Site 1904)

Adana, Turkey, 01130

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1908)

Ankara, Turkey, 06100

Uludag Universitesi Tip Fakultesi ( Site 1914)

Bursa, Turkey, 16059

Ankara Sehir Hastanesi ( Site 1903)

Cankaya - Ankara, Turkey, 06490

Trakya Uni. Tip Fakultesi ( Site 1911)

Edirne, Turkey, 22030

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1906)

Istanbul, Turkey, 34098

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 1912)

Istanbul, Turkey, 34899

Ege Universitesi Tip Fakultesi Hastanesi ( Site 1901)

Izmir, Turkey, 35100

Medical Park Izmir Hospital ( Site 1900)

Izmir, Turkey, 35575

Kocaeli Universitesi Tip Fakultesi ( Site 1909)

Kocaeli, Turkey, 41380

Inonu Universitesi Tip Fakultesi ( Site 1907)

Malatya, Turkey, 44280

Karadeniz Teknik Universitesi ( Site 1910)

Trabzon, Turkey, 61080

Ukraine

MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2005)

Kryviy Rih, Dnipropetrovsk Region, Ukraine, 50048

Cherkasy Regional Hospital ( Site 2020)

Cherkasy, Ukraine, 18009

Regional Clinical Onco Dispensary_ State Medical University ( Site 2012)

Chernivtsy, Ukraine, 58013

Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC ( Site 2000)

Dnipropetrovsk, Ukraine, 49102

MI Prykarpatskyi Clinical Oncology Centrum ( Site 2009)

Ivano-Frankivsk, Ukraine, 76018

PP PPC Acinus Medical and Diagnostic Centre ( Site 2002)

Kropyvnytskyi, Ukraine, 25006

National Cancer Institute of the MoH of Ukraine ( Site 2015)

Kyiv, Ukraine, 03002

Kyiv City Clinical Oncological Center ( Site 2014)

Kyiv, Ukraine, 03115

Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2003)

Lviv, Ukraine, 79031

MI Odessa Regional Oncological Centre ( Site 2004)

Odesa, Ukraine, 65055

United Kingdom

Royal Cornwall Hospital ( Site 1325)

Truro, Cornwall, United Kingdom, TR1 3LJ

The Royal Marsden NHS Foundation Trust. ( Site 1326)

Sutton, Surrey, United Kingdom, SM2 5PT

Belfast City Hospital ( Site 1302)

Belfast, United Kingdom, BT9 7AB

Royal Free NHS Foundation Trust ( Site 1324)

London, United Kingdom, NW3 2QG

St. Georges University Hospital NHS Foundation Trust ( Site 1321)

London, United Kingdom, SW17 0QT

The Royal Marsden NHS Foundation Trust.. ( Site 1327)

London, United Kingdom, SW3 6JJ

The Christie NHS Foundation Trust ( Site 1301)

Manchester, United Kingdom, M20 4BX

Mount Vernon Cancer Centre ( Site 1307)

Northwood, United Kingdom, HA6 2RN

Royal Wolverhampton Hospitals NHS Trust ( Site 1323)

Wolverhampton, United Kingdom, WV10 0QP

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] December 11, 2020

More Information

Additional Information:

Merck Oncology Clinical Trials Information 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03302234
• Other Study ID Numbers: 3475-598; MK-3475-598 ( Other Identifier: Merck ); KEYNOTE-598 ( Other Identifier: Merck ); 2016-004364-20 ( EudraCT Number )
• First Posted: October 5, 2017
• Results First Posted: September 10, 2021
• Last Update Posted: October 4, 2022
• Last Verified: September 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
• URL: http://engagezone.msd.com/ds_documentation.php

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

Programmed Cell Death Receptor 1 (PD-1); Programmed Cell Death Receptor Ligand 1 (PD-L1); Cytotoxic T-lymphocyte-associated protein 4 (CTLA4); PD1; PD-1; PDL1; PD-L1; CTLA4

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Pembrolizumab; Ipilimumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action