Carcinoma, Non-Small-Cell LungPhase 3NCT03302234
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 study testing Pembrolizumab and Ipilimumab in people with Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC at 187 sites in 24 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Pembrolizumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 568 participants
- Where
- 187 sitesin 24 countries
- Study dates
- 14 Dec 2017to 7 Sep 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
Trial locations and contacts
187 sites in 24 countries.
187 sites in 24 countries
United States25 sites
Texas Oncology-Arlington South ( Site 8006)
Arlington, Texas, 76014
Boston Medical Center ( Site 0025)
Boston, Massachusetts, 02118
Disney Family Cancer Center ( Site 0035)
Burbank, California, 91505
Lahey Hospital & Medical Center ( Site 0020)
Burlington, Massachusetts, 01805
University of Tennessee Erlanger Oncology & Hematology ( Site 0026)
Chattanooga, Tennessee, 37403
The Ohio State University Wexner Medical Center ( Site 0016)
Columbus, Ohio, 43210
Mid Ohio Oncology/Hematology Inc. ( Site 0003)
Columbus, Ohio, 43219
Texas Oncology-Methodist Dallas Cancer Center ( Site 8000)
Dallas, Texas, 75203
Texas Oncology-Flower Mound ( Site 8007)
Flower Mound, Texas, 75028
Greenville Health System ( Site 8010)
Greenville, South Carolina, 29615
Tennessee Cancer Specialists ( Site 0017)
Knoxville, Tennessee, 37909
Texas Oncology-Longview Cancer Center ( Site 8009)
Longview, Texas, 75601
University of Wisconsin Carbone Cancer Center ( Site 0004)
Madison, Wisconsin, 53792
Medical College of Wisconsin Clinical Cancer Center ( Site 0027)
Milwaukee, Wisconsin, 53226
Pacific Cancer Care ( Site 0001)
Monterey, California, 93940
Icahn School of Medicine at Mount Sinai ( Site 0034)
New York, New York, 10029
Florida Hospital Cancer Institute ( Site 0009)
Orlando, Florida, 32804
Mercy Health-Paducah Medical Oncology and Hematology ( Site 0018)
Paducah, Kentucky, 42003
Mayo Clinic Cancer Center ( Site 0007)
Phoenix, Arizona, 85054
Providence Cancer Institute, Franz Clinic - Eastside ( Site 0031)
Portland, Oregon, 97213
John Wayne Cancer Institute ( Site 0021)
Santa Monica, California, 90404
New England Cancer Specialists ( Site 0019)
Scarborough, Maine, 04074
Holy Name Medical Center ( Site 0022)
Teaneck, New Jersey, 07666
Northwest Cancer Specialists, P.C. ( Site 8001)
Vancouver, Washington, 98684
Virginia Mason Memorial- North Star Lodge Cancer Center ( Site 0033)
Yakima, Washington, 98902
Turkey (Türkiye)12 sites
Acibadem Adana Hastanesi ( Site 1904)
Adana, 01130
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1908)
Ankara, 06100
Uludag Universitesi Tip Fakultesi ( Site 1914)
Bursa, 16059
Ankara Sehir Hastanesi ( Site 1903)
Cankaya - Ankara, 06490
Trakya Uni. Tip Fakultesi ( Site 1911)
Edirne, 22030
Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 1906)
Istanbul, 34098
Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi ( Site 1912)
Istanbul, 34899
Ege Universitesi Tip Fakultesi Hastanesi ( Site 1901)
Izmir, 35100
Medical Park Izmir Hospital ( Site 1900)
Izmir, 35575
Kocaeli Universitesi Tip Fakultesi ( Site 1909)
Kocaeli, 41380
Inonu Universitesi Tip Fakultesi ( Site 1907)
Malatya, 44280
Karadeniz Teknik Universitesi ( Site 1910)
Trabzon, 61080
Ukraine10 sites
Cherkasy Regional Hospital ( Site 2020)
Cherkasy, 18009
Regional Clinical Onco Dispensary_ State Medical University ( Site 2012)
Chernivtsy, 58013
Dnipropetrovsk City Multidiscipline Clinical Hosp.4 of DRC ( Site 2000)
Dnipropetrovsk, 49102
MI Prykarpatskyi Clinical Oncology Centrum ( Site 2009)
Ivano-Frankivsk, 76018
PP PPC Acinus Medical and Diagnostic Centre ( Site 2002)
Kropyvnytskyi, 25006
MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2005)
Kryviy Rih, Dnipropetrovsk Oblast, 50048
National Cancer Institute of the MoH of Ukraine ( Site 2015)
Kyiv, 03002
Kyiv City Clinical Oncological Center ( Site 2014)
Kyiv, 03115
Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 2003)
Lviv, 79031
MI Odessa Regional Oncological Centre ( Site 2004)
Odesa, 65055
Brazil9 sites
Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 0312)
Barretos, 14784-400
CEPON Centro de Pesquisa Oncológicas ( Site 0307)
Florianópolis, 88034-000
Hospital Nossa Senhora da Conceicao ( Site 0306)
Porto Alegre, Rio Grande do Sul, 91350-200
Inst de Medicina Integral Professor Fernando Figueira- IMIP ( Site 0302)
Recife, Pernambuco, 50070-550
Clinica de Hematologia e Oncologia Viver Ltda ( Site 0305)
Santa Maria, Rio Grande do Sul, 97015-513
Instituto do Cancer de Sao Paulo - ICESP ( Site 0300)
São Paulo, São Paulo, 01246-000
Hospital Alemao Oswaldo Cruz ( Site 0311)
São Paulo, São Paulo, 01323-020
Escola Paulista de Medicina - UNIFESP ( Site 0304)
São Paulo, São Paulo, 04024-002
Hospital do Servidor Publico do Estado ( Site 0308)
São Paulo, 04039-004
France9 sites
Institut Bergonie ( Site 0803)
Bordeaux, 33076
CHU de Brest. Hopital Morvan ( Site 0800)
Brest, 29200
Centre Hopitalier Intercommunal Creteil ( Site 0802)
Créteil, 94010
Centre Hospitalier Le Mans ( Site 0804)
Le Mans, 72037
C.H.R.U de Lille - Hopital Calmette ( Site 0805)
Lille, 59037
Hopital Nord du Marseille ( Site 0808)
Marseille, Cedex 20, 13015
Hopital Tenon ( Site 0810)
Paris, 75020
Nouvel Hopital Civil ( Site 0809)
Strasbourg, 67091
CHU de Toulouse - Hopital Larrey ( Site 0801)
Toulouse, 31059
Hungary9 sites
Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1502)
Budapest, 1121
Orszagos Koranyi TBC es Pulmonologiai Intezet ( Site 1506)
Budapest, 1122
Orszagos Onkologiai Intezet ( Site 1509)
Budapest, 1122
Debreceni Egyetem Klinikai Kozpont ( Site 1511)
Debrecen, 4032
Veszprem Megyei Tudogyogyintezet ( Site 1503)
Farkasgyepű, 8582
Petz Aladar Megyei Oktato Korhaz ( Site 1505)
Győr, 9024
Bekes Megyei Pandy Kalman Korhaz. ( Site 1507)
Gyula, 5700
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz ( Site 1504)
Székesfehérvár, 8000
Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ( Site 1501)
Szolnok, 5000
South Africa9 sites
Clinton Onclogy Clinic ( Site 1804)
Alberton, Gauteng, 1448
Universitas Annex National Hospital ( Site 1800)
Bloemfontein, Free State, 9301
Vincent Pallotti Hospital ( Site 1811)
Cape Town, 7405
University of Stellenbosch and Tygerberg Hospital ( Site 1810)
Cape Town, 8000
Dr G.A. Landers Specialist Oncologist ( Site 1803)
Durban, 4001
Charlotte Maxeke Johannesburg Academic Hospital ( Site 1806)
Johannesburg, 2193
Sandton Oncology Medical Group PTY LTD ( Site 1807)
Johannesburg, 2196
GVI Oncology Clinical Research Centre ( Site 1802)
Kraaifontein, 7570
Wilgers Oncology Centre ( Site 1808)
Pretoria, Gauteng, 0081
United Kingdom9 sites
Belfast City Hospital ( Site 1302)
Belfast, BT9 7AB
Royal Free NHS Foundation Trust ( Site 1324)
London, NW3 2QG
St. Georges University Hospital NHS Foundation Trust ( Site 1321)
London, SW17 0QT
The Royal Marsden NHS Foundation Trust.. ( Site 1327)
London, SW3 6JJ
The Christie NHS Foundation Trust ( Site 1301)
Manchester, M20 4BX
Mount Vernon Cancer Centre ( Site 1307)
Northwood, HA6 2RN
The Royal Marsden NHS Foundation Trust. ( Site 1326)
Sutton, Surrey, SM2 5PT
Royal Cornwall Hospital ( Site 1325)
Truro, Cornwall, TR1 3LJ
Royal Wolverhampton Hospitals NHS Trust ( Site 1323)
Wolverhampton, WV10 0QP
Argentina8 sites
Hospital Aleman ( Site 0208)
Buenos Aires, C1118AAT
Hospital Privado Centro Medico Cordoba ( Site 0206)
Córdoba, X5016KEH
Centro Oncologico Riojano Integral ( Site 0203)
La Rioja, F5300COE
Sanatorio Parque ( Site 0201)
Rosario, Santa Fe Province, S2000DSV
Sanatorio Britanico ( Site 0205)
Rosario, S2000CVB
Instituto de Oncologia de Rosario ( Site 0200)
Rosario, S2000KZE
Centro Medico San Roque ( Site 0207)
San Miguel de Tucumán, T4000IAK
Centro de Investigaciones Clinicas - Clinica Viedma ( Site 0202)
Viedma, Río Negro Province, R8500ACE
Germany8 sites
Evangelische Lungenklinik Berlin ( Site 0903)
Berlin, 13125
Vivantes Klinikum Spandau ( Site 0910)
Berlin, 13585
HELIOS Klinikum Emil von Behring ( Site 0905)
Berlin, 14165
SRH Waldklinikum Gera GmbH ( Site 0907)
Gera, 07548
LungenClinic Grosshansdorf GmbH ( Site 0908)
Großhansdorf, 22927
Universitaetsklinikum Heidelberg ( Site 0900)
Heidelberg, 69126
Universitaetsklinikum Leipzig ( Site 0919)
Leipzig, 04103
Universitaetsklinikum Schleswig Holstein. ( Site 0918)
Lübeck, 23538
Italy8 sites
ASST Spedali Civili ( Site 1001)
Brescia, 25123
Ospedale Mater Salutis ( Site 1005)
Legnago, Verona, 37045
Istituto Europeo di Oncologia ( Site 1007)
Milan, 20141
Ospedale San Gerardo ASST Monza ( Site 1002)
Monza, 20900
AORN dei Colli Plesso Monaldi ( Site 1003)
Naples, 80131
Ospedale Santa Maria della Misericordia ( Site 1008)
Perugia, 06132
Humanitas Research Hospital ( Site 1004)
Rozzano, Milano, 20089
IRCCS Casa Sollievo della Sofferenza ( Site 1009)
San Giovanni Rotondo (FG), Foggia, 71013
Poland8 sites
Powiatowe Centrum Zdrowia w Brzezinach ( Site 1615)
Brzeziny, 95-060
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1609)
Bydgoszcz, 85-796
Przychodnia Lekarska Komed ( Site 1602)
Konin, 62-500
Szpital Wojewodzki w Koszalinie im. Mikolaja Kopernika ( Site 1614)
Koszalin, West Pomeranian Voivodeship, 75-581
Samodzielny Publiczny Zespol Gruzlicy i Chorob Pluc ( Site 1607)
Olsztyn, 10-357
MED-POLONIA Sp. z o.o. ( Site 1605)
Poznan, 60-693
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie ( Site 1600)
Warsaw, 02-781
Dolnoslaskie Centrum Onkologii. ( Site 1616)
Wroclaw, Lower Silesian Voivodeship, 53-413
Canada7 sites
Tom Baker Cancer Centre ( Site 0119)
Calgary, Alberta, T2N 4N2
CIUSSS du Saguenay-Lac-St-Jean ( Site 0115)
Chicoutimi, Quebec, G7H 5H6
CISSS de la Monteregie-Centre ( Site 0100)
Greenfield Park, Quebec, J4V 2H1
CISSS-CA Hotel-Dieu de Levis ( Site 0108)
Lévis, Quebec, G6V 3Z1
CIUSSS Ouest de l'Ile - St-Mary's Hospital ( Site 0107)
Montreal, Quebec, H3T 1M5
St-Jerome Medical Research Inc ( Site 0113)
Saint-Jérôme, Quebec, J7Z 5T3
CancerCare Manitoba ( Site 0106)
Winnipeg, Manitoba, R3E 0V9
Spain7 sites
Hospital Germans Trias i Pujol ( Site 1207)
Badalona, Barcelona, 08916
Hospital Universitari Vall d Hebron ( Site 1211)
Barcelona, 08035
Hospital San Pedro de Alcantara ( Site 1208)
Cáceres, Extremadura, 10003
Hospital Duran i Reynals ( Site 1201)
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Insular de Gran Canaria ( Site 1203)
Las Palmas de Gran Canaria, Gran Canaria, 35001
Hospital Fundacion Jimenez Diaz - Clin. Concepcion ( Site 1209)
Madrid, 28040
Hospital Universitario Virgen del Rocio ( Site 1200)
Seville, 41013
Taiwan7 sites
Changhua Christian Hospital ( Site 2406)
Changhua, 50006
Chang Gung Medical Foundation - Kaohsiung ( Site 2404)
Kaohsiung City, 833
China Medical University Hospital ( Site 2403)
Taichung, 404
National Cheng Kung University Hospital ( Site 2401)
Tainan, 70457
National Taiwan University Hospital ( Site 2400)
Taipei, 10048
Mackay Memorial Hospital ( Site 2405)
Taipei, 104
Chang Gung Memorial Hospital - Linkou Branch ( Site 2402)
Taoyuan, 33305
Mexico6 sites
Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 0603)
Guadalajara, Jalisco, 44200
Medical Care and Research S.A. de C.V. ( Site 0602)
Mérida, Yucatán, 97070
Grupo Medico Camino SC ( Site 0607)
Mexico City, 03310
Medica Sur S.A.B de C.V. ( Site 0608)
Mexico City, 14050
Avix Investigacion Clinica S.C. ( Site 0600)
Monterrey, N.L., 64710
Oncologica de Puebla SA de CV ( Site 0606)
Puebla City, 72530
Peru6 sites
Centro Especializado de Enfermedades Neoplasicas SRL-CEEN SRL ( Site 0710)
Arequipa, 04000
Instituto Regional de Enfermedades Neoplasicas del Sur IRENSUR ( Site 0704)
Arequipa, 04000
Hospital Nacional Guillermo Almenara Irigoyen ( Site 0705)
La Victoria, Lima region, 15033
Clinica Internacional Sede San Borja ( Site 0701)
Lima, 15036
Hospital Nacional Cayetano Heredia ( Site 0706)
Lima, 15102
Clinica Peruano Americana S.A. ( Site 0703)
Trujillo, 13007
Thailand6 sites
Chulalongkorn Hospital ( Site 2561)
Bangkok, 10330
Pramongkutklao Hospital ( Site 2564)
Bangkok, 10400
Siriraj Hospital ( Site 2562)
Bangkok, 10700
Khon Kaen University ( Site 2565)
Khon Kaen, 40002
Bangkok Hospital Chiangmai ( Site 2560)
Mueang, Chiang Mai, 50000
Ramathibodi Hospital. ( Site 2563)
Ratchthevee, Bangkok, 10400
Australia5 sites
Chris OBrien Lifehouse ( Site 2100)
Camperdown, 2050
The Townsville Hospital ( Site 2103)
Douglas, 4814
St Vincents Hospital Melbourne ( Site 2101)
Fitzroy, 3065
Fiona Stanley Hospital ( Site 2105)
Perth, Western Australia, 6150
Mater Cancer Care Centre ( Site 2102)
South Brisbane, Queensland, 4101
Chile5 sites
Soc. Prosalud Montes y Orlandi Ltda (Orlandi Oncologia) ( Site 0401)
Santiago, 7500006
Pontificia Universidad Catolica de Chile ( Site 0404)
Santiago, 8330032
Instituto Nacional del Cancer ( Site 0406)
Santiago, 8380455
Clinica Universidad Catolica del Maule ( Site 0413)
Talca, El Maule, 3465584
Hospital Clinico Vina del Mar ( Site 0400)
Viña del Mar, 2520000
Colombia5 sites
Centro de Investigacion Clinica del Country ( Site 0500)
Bogotá, 110221
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 0506)
Bogotá, 110311
Hospital Pablo Tobon Uribe ( Site 0505)
Medellín, Antioquia, 050034
Oncomedica S.A. ( Site 0502)
Montería, 230002
Instituto Cancerologico de Narino Ltda ( Site 0504)
Pasto, 520001
South Korea4 sites
Seoul National University Hospital ( Site 2303)
Seoul, 03080
Severance Hospital Yonsei University Health System ( Site 2300)
Seoul, 03722
Asan Medical Center ( Site 2302)
Seoul, 05505
Samsung Medical Center ( Site 2301)
Seoul, 06351
Ireland3 sites
Beaumont Hospital ( Site 1312)
Dublin, D09 V2N0
St James Hospital ( Site 1401)
Dublin, Dublin 8
University Hospital Limerick ( Site 1403)
Limerick, V94 F858
Latvia2 sites
Pauls Stradins Clinical University Hospital ( Site 1100)
Riga, 1002
Riga East Clinical University Hospital ( Site 1111)
Riga, 1079
About this study
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)
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.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Pembrolizumab, Ipilimumab, Placebo
- Keywords
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Parkinson Disease 4, Autosomal Dominant Lewy Body, Diabetes Mellitus, Insulin-Dependent, 12
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called KEYTRUDA®, MK-3475
Administered as an intravenous (IV) infusion every 3 weeks (Q3W)
IpilimumabBiological
Also called YERVOY®
Administered as an IV infusion every 6 weeks (Q6W)
PlaceboOther
Normal saline solution administered as an IV infusion Q6W
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Ipilimumab | Experimental | 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. Receives: Biological: Pembrolizumab; Biological: Ipilimumab |
| Pembrolizumab + Placebo | Active comparator | 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. Receives: Biological: Pembrolizumab; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to approximately 32 months (through data cut-off date 01 Sep 2020)
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 18
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2017
- Study start14 Dec 2017
- Primary completion1 Sep 2020
- Study completion7 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 568 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03302234
- Sponsor's protocol ID
- 3475-598
- Other IDs
- MK-3475-598, KEYNOTE-598, 2016-004364-20, 2016
- Status last verified
- Sep 2023
- First submitted
- 26 Sep 2017
- Last updated
- 26 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
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.
PubMed 33513313
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03302234
- Acronym / sponsor ID
- 3475-598
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Keywords
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 568 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 14 Dec 2017 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 7 Sep 2022 (actual)
- First posted
- 5 Oct 2017 (actual)
- Results
- Posted 10 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + Ipilimumab | Experimental | Biological: Pembrolizumab, Biological: IpilimumabParticipants 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. |
| Pembrolizumab + Placebo | Active comparator | Biological: Pembrolizumab, Other: PlaceboParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KEYTRUDA®, MK-3475Administered as an intravenous (IV) infusion every 3 weeks (Q3W) | Biological | Pembrolizumab + Ipilimumab, Pembrolizumab + Placebo |
| IpilimumabAlso: YERVOY®Administered as an IV infusion every 6 weeks (Q6W) | Biological | Pembrolizumab + Ipilimumab |
| PlaceboNormal saline solution administered as an IV infusion Q6W | Other | Pembrolizumab + Placebo |
Primary outcome
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.
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.
6 secondary outcomes
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)
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)
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)
Number of Participants Who Experienced an Adverse Event (AE)
Time frame: Up to approximately 27 months
Number of Participants Who Discontinued Study Treatment Due to an AE
Time frame: 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
Time frame: Baseline, Week 18
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33513313Boyer 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.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pd
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
187 sites in 24 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pembrolizumab and Ipilimumab in people with Carcinoma, Non-Small-Cell Lung, run by Merck Sharp & Dohme LLC at 187 sites in 24 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 187 sites in United States, Turkey (Türkiye), Ukraine, Brazil, France and 19 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: Up to approximately 32 months (through data cut-off date: 01 Sep 2020)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03302234, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2023.