Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)

Renal Cell Carcinoma Clinical Trial

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03142334
• Other study ID #: 3475-564
• Secondary ID: 173704MK-3475-56
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 9, 2017
• Est. completion date: December 28, 2025

Study information

• Verified date: June 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of pembrolizumab (MK-3475) in the adjuvant treatment of adult participants who have undergone nephrectomy and have intermediate-high risk, high risk, or M1 no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The primary study hypothesis is that pembrolizumab is superior to placebo with respect to Disease-free Survival (DFS) as assessed by the Investigator in male and female participants with intermediate-high risk, high risk and M1 NED RCC.

Description:

Participants will be assigned to receive study treatment until disease recurrence, unacceptable adverse events (AEs), intercurrent illness that prevents further administration of treatment, Investigator's decision to withdraw the participant, noncompliance with study treatment or procedural requirements, administrative reasons requiring cessation of treatment, or until the participant has received 17 cycles of study treatment (approximately 1 year). Each cycle is 3 weeks long. With Protocol Amendment 02 (dated 04 Sep 2019), the secondary study objectives for the evaluation of pharmacokinetic (PK) parameters and the presence of pembrolizumab antidrug antibodies (ADA) were reclassified as tertiary study objectives.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 994
• Est. completion date: December 28, 2025
• Est. primary completion date: December 14, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed diagnosis of renal cell carcinoma (RCC) with clear cell component with or without sarcomatoid features
• Female participants of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study treatment
• Male participants of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study treatment through 120 days after the last dose of study treatment
• Has intermediate-high risk, high risk, or M1 no evidence of disease (NED) RCC as defined by the following pathological tumor-node-metastasis and Fuhrman grading

status:

1. Intermediate-high risk RCC: pT2, Grade 4 or sarcomatoid, N0, M0; pT3, Any Grade, N0, M0

2. High risk RCC: pT4, Any Grade N0, M0; pT Any stage, Any Grade, N+, M0

3. M1 NED RCC participants who present not only with the primary kidney tumor but also solid, isolated, soft tissue metastases that can be completely resected at one of the following: the time of nephrectomy (synchronous) or, =1 year from nephrectomy (metachronous)

• Has received no prior systemic therapy for advanced RCC
• Has undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins
• Must have undergone a nephrectomy and/or metastasectomy =28 days prior to signing informed consent and =12 weeks prior to randomization
• Must be tumor-free as assessed by the Investigator and validated by either computed tomography (CT) or magnetic resonance imaging (MRI) scan of the brain and chest, abdomen, and pelvis and a bone scan =28 days from randomization
• Must have provided adequate tissue per the following: Nephrectomy only: tissue from nephrectomy (required); Synchronous M1 NED: tissue from nephrectomy (required) AND, metastasectomy tissue (if available); Metachronous M1 NED: tissue from metastasectomy (required) AND, nephrectomy tissue (if available)
• Has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1
• Has adequate organ function

Exclusion Criteria:

• Has had major surgery, other than nephrectomy and/or resection of pre-existing metastases for M1 NED participants, within 12 weeks prior to randomization
• Has received prior radiotherapy for RCC
• Has pre-existing brain or bone metastatic lesions
• Has residual thrombus post nephrectomy in the vena renalis or vena cava
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
• 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). Replacement therapy is allowed
• Has a known additional malignancy that is progressing or required active treatment =3 years ago. Exceptions include early-stage cancers (carcinoma in situ or Stage 1) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer, or in situ breast cancer that has undergone potentially curative therapy
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
• Has an active infection requiring systemic therapy
• Has a history of, or is currently on, dialysis
• Has a known history of human immunodeficiency virus (HIV) infection
• Has known active hepatitis B or hepatitis C virus infection
• Has a known history of active tuberculosis (Bacillus tuberculosis)
• Has had a prior solid organ transplant
• Has severe hypersensitivity (= Grade 3) to pembrolizumab and/or any of its excipients
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the Screening visit through 120 days after the last dose of study treatment
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a Merck pembrolizumab (MK-3475) clinical trial
• Has received prior anticancer therapy, monoclonal antibody, chemotherapy, or an investigational agent or device within 4 weeks or 5 half-lives (whichever is longer) before first dose of study treatment or not recovered (i.e., must be = Grade 1 or at Baseline) from AEs due to previously administered agents
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Placebo
IV infusion

Locations

Country	Name	City	State
Argentina	Fundacion Favaloro ( Site 1110)	Buenos Aires
Argentina	Instituto de Investigaciones Metabolicas -I.D.I.M.- ( Site 1113)	Buenos Aires
Argentina	Instituto Medico Alexander Fleming ( Site 1105)	Buenos Aires
Argentina	Centro Oncologico Riojano Integral ( Site 1101)	La Rioja
Argentina	Centro Oncologico de Integracion Regional. COIR ( Site 1109)	Mendoza
Argentina	Instituto de Oncologia de Rosario ( Site 1100)	Rosario
Argentina	Sanatorio Britanico ( Site 1106)	Rosario
Argentina	Sanatorio Parque ( Site 1104)	Rosario	Santa Fe
Argentina	Centro Medico San Roque ( Site 1108)	Tucuman
Argentina	Centro de Investigaciones Clinicas - Clinica Viedma ( Site 1102)	Viedma	Rio Negro
Australia	Ballarat Health Services ( Site 0705)	Ballarat
Australia	Bendigo Cancer Centre ( Site 0704)	Bendigo	Victoria
Australia	Box Hill Hospital ( Site 0701)	Box Hill	Victoria
Australia	Saint George Hospital [Kogarah, Australia] ( Site 0707)	Kogarah	New South Wales
Australia	Adelaide Cancer Centre ( Site 0703)	Kurralta Park	South Australia
Australia	Macquarie University Hospital ( Site 0700)	Macquarie Park	New South Wales
Australia	Fiona Stanley Hospital ( Site 0702)	Murdoch	Western Australia
Brazil	Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1002)	Barretos	Sao Paulo
Brazil	Universidade de Caxias do Sul ( Site 1004)	Caxias do Sul	Rio Grande Do Sul
Brazil	Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1012)	Curitiba	PR
Brazil	Fundacao Dr Amaral Carvalho ( Site 1005)	Jau	Sao Paulo
Brazil	Hospital Bruno Born ( Site 1015)	Lajeado	RS
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 1013)	Natal	Rio Grande Do Norte
Brazil	Hospital Nossa Senhora da Conceicao ( Site 1000)	Porto Alegre	RS
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1001)	Porto Alegre	RS
Brazil	Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1016)	Ribeirao Preto
Brazil	Casa de Saude Santa Marcelina ( Site 1006)	Sao Paulo	SP
Brazil	Instituto do Cancer de Sao Paulo - ICESP ( Site 1010)	Sao Paulo	SP
Brazil	COT Centro Oncologico do Triangulo Ltda ( Site 1014)	Uberlandia
Canada	William Osler Health System ( Site 0115)	Brampton	Ontario
Canada	CIUSSS du Saguenay-Lac-St-Jean ( Site 0113)	Chicoutimi	Quebec
Canada	Juravinski Cancer Centre ( Site 0117)	Hamilton	Ontario
Canada	CISSS-CA Hotel Dieu de Levis ( Site 0111)	Lévis	Quebec
Canada	London Regional Cancer Program - London HSC ( Site 0107)	London	Ontario
Canada	Dr. Leon Richard Oncology Centre ( Site 0106)	Moncton	New Brunswick
Canada	CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0118)	Montreal	Quebec
Canada	Lakeridge Health ( Site 0108)	Oshawa	Ontario
Canada	Allan Blair Cancer Centre ( Site 0116)	Regina	Saskatchewan
Canada	Saskatoon Cancer Centre ( Site 0105)	Saskatoon	Saskatchewan
Canada	St-Jerome Medical Research Inc ( Site 0103)	St-Jerome	Quebec
Canada	Niagara Health System - St. Catharines ( Site 0120)	St. Catharines	Ontario
Canada	CancerCare Manitoba ( Site 0119)	Winnipeg	Manitoba
Chile	Centro Oncologico Antofagasta ( Site 0914)	Antofagasta
Chile	Hospital Regional de La Serena ( Site 0907)	La Serena
Chile	Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0910)	Rancagua
Chile	Fundacion Arturo Lopez Perez FALP ( Site 0902)	Santiago
Chile	Health and Care Chile ( Site 0901)	Santiago
Chile	Hospital Clinico Universidad de Chile ( Site 0905)	Santiago
Chile	Hospital Militar de Santiago ( Site 0911)	Santiago
Chile	Instituto Nacional del Cancer ( Site 0912)	Santiago	Region Metropolitana
Chile	Iram Cancer Research ( Site 0909)	Santiago
Chile	Pontificia Universidad Catolica de Chile ( Site 0904)	Santiago
Chile	Sociedad de Investigaciones Medicas Limitadas ( Site 0913)	Temuco
Chile	Oncocentro ( Site 0900)	Vina del Mar
Colombia	Clinica de la Costa Ltda. ( Site 0804)	Barranquilla	Atlantico
Colombia	Administradora Country SA - Clinica del Country ( Site 0808)	Bogota
Colombia	Fundacion CardioInfantil Instituto de Cardiologia ( Site 0803)	Bogota
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 0807)	Bogota	Cundinamarca
Colombia	Hospital Pablo Tobon Uribe. ( Site 0805)	Medellin	Antioquia
Colombia	Oncomedica S.A. ( Site 0801)	Monteria
Colombia	Oncologos del Occidente S.A. ( Site 0800)	Pereira	Risaralda
Colombia	Sociedad de Hematologia y Oncologia del Cesar ( Site 0809)	Valledupar	Cesar
Czechia	FN Brno. ( Site 1501)	Brno
Czechia	Nemocnice Novy Jicin a.s. Clen skupiny AGEL ( Site 1506)	Novy Jicin
Czechia	Fakultni nemocnice Olomouc ( Site 1502)	Olomouc
Czechia	Fakultni nemocnice Ostrava ( Site 1507)	Ostrava
Czechia	Thomayerova nemocnice ( Site 1505)	Praha 4
Czechia	Fakultni nemocnice v Motole ( Site 1504)	Praha 5
Czechia	Nemocnice Na Bulovce ( Site 1503)	Praha 8
Finland	HYKS ( Site 2300)	Helsinki
Finland	Keski-Suomen keskussairaala ( Site 2303)	Jyvaskyla
Finland	Oulun yliopistollinen sairaala - OYS ( Site 2304)	Oulu
Finland	TAYS ( Site 2301)	Tampere
Finland	TYKS ( Site 2302)	Turku
France	ICO Centre Paul Papin ( Site 2208)	Angers
France	CHU Besancon - Hopital Jean Minjoz ( Site 2200)	Besancon
France	Hopital Saint Andre ( Site 2202)	Bordeaux
France	Hopital La Timone ( Site 2204)	Marseille
France	CHU Saint-Eloi ( Site 2203)	Montpellier
France	Centre Antoine Lacassagne ( Site 2211)	Nice
France	Hopital Europeen Georges Pompidou ( Site 2206)	Paris
France	Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 2212)	Pierre Benite
France	Centre Eugene Marquis ( Site 2209)	Rennes
France	Centre Rene Gauducheau ICO ( Site 2207)	Saint Herblain
France	Institut Claudius Regaud IUCT Oncopole ( Site 2201)	Toulouse
Germany	Campus Charite Mitte ( Site 2120)	Berlin
Germany	Helios Klinikum Berlin Buch ( Site 2125)	Berlin
Germany	Universitaetsklinikum Bonn ( Site 2110)	Bonn
Germany	Universitaetsklinikum der Technischen Universitaet Dresden ( Site 2113)	Dresden
Germany	Universitatsklinikum Dusseldorf ( Site 2108)	Dusseldorf
Germany	Universitaetsklinikum Erlangen. Waldkrankenhaus ( Site 2102)	Erlangen
Germany	Universitaetsklinikum Essen ( Site 2116)	Essen
Germany	Universitaetsklinikum Frankfurt ( Site 2121)	Frankfurt
Germany	Universitaetsklinikum Freiburg ( Site 2119)	Freiburg
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 2118)	Hamburg
Germany	Universitaetsklinikum Jena. ( Site 2104)	Jena
Germany	Universitaetsklinikum Schleswig Holstein ( Site 2109)	Luebeck
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 2111)	Mainz
Germany	Studienpraxis Urologie ( Site 2115)	Nuertingen
Germany	Krankenhaus der Barmherzigen Brueder Trier ( Site 2117)	Trier
Germany	Universitaetsklinikum Tuebingen ( Site 2100)	Tuebingen
Ireland	Beaumont Hospital ( Site 1611)	Dublin
Ireland	St Vincents University Hospital ( Site 1610)	Dublin
Ireland	University Hospital Waterford ( Site 1614)	Waterford
Italy	Medical Oncology Ospedale San Donato ( Site 2004)	Arezzo
Italy	Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 2012)	Meldola
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2005)	Milano
Italy	Istituto Europeo di Oncologia ( Site 2000)	Milano
Italy	Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 2006)	Modena
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 2003)	Napoli
Italy	Ospedale San Luigi Gonzaga ( Site 2010)	Orbassano	Torino
Italy	Istituto Nazionale Tumori Regina Elena ( Site 2009)	Roma
Japan	Akita University Hospital ( Site 0433)	Akita
Japan	Harasanshin Hospital ( Site 0402)	Fukuoka
Japan	Kyushu University Hospital ( Site 0413)	Fukuoka
Japan	Saitama Medical University International Medical Center ( Site 0404)	Hidaka	Saitama
Japan	Nara Medical University Hospital ( Site 0416)	Kashihara	Nara
Japan	Kagawa University Hospital ( Site 0419)	Kita-gun	Kagawa
Japan	Kumamoto University Hospital ( Site 0434)	Kumamoto
Japan	Nagano Municipal Hospital ( Site 0429)	Nagano
Japan	Nagoya University Hospital ( Site 0431)	Nagoya	Aichi
Japan	Niigata University Medical & Dental Hospital ( Site 0421)	Niigata
Japan	Osaka City University Hospital ( Site 0428)	Osaka
Japan	Osaka International Cancer Institute ( Site 0401)	Osaka
Japan	Kindai University Hospital ( Site 0411)	Osakasayama	Osaka
Japan	Osaka Rosai Hospital ( Site 0418)	Sakai	Osaka
Japan	Sapporo Medical University Hospital ( Site 0424)	Sapporo	Hokkaido
Japan	Japan Community Health care Organization Sendai Hospital ( Site 0430)	Sendai	Miyagi
Japan	Keio University Hospital ( Site 0407)	Tokyo
Japan	Nippon Medical School Hospital ( Site 0400)	Tokyo
Japan	Toranomon Hospital ( Site 0426)	Tokyo
Japan	Toyama University Hospital ( Site 0432)	Toyama
Japan	Yamaguchi University Hospital ( Site 0406)	Ube	Yamaguchi
Korea, Republic of	National Cancer Center ( Site 0304)	Goyang-si	Gyeonggi-do
Korea, Republic of	Asan Medical Center ( Site 0300)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 0301)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0302)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0303)	Seoul
Netherlands	Amphia Ziekenhuis Breda ( Site 1901)	Breda
Netherlands	Maastricht Universitair Medisch Centrum - MUMC ( Site 1902)	Maastricht
Netherlands	Franciscus Gasthuis ( Site 1903)	Rotterdam
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny ( Site 1309)	Brzozow
Poland	Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1307)	Bytom
Poland	Wojewodzkie Centrum Onkologii Copernicus ( Site 1304)	Gdansk
Poland	Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o. ( Site 1302)	Gdynia
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1323)	Gliwice
Poland	Przychodnia Lekarska Komed ( Site 1306)	Konin
Poland	Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1322)	Koscierzyna	Pomorskie
Poland	Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1310)	Krakow
Poland	Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1315)	Lublin
Poland	Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina ( Site 1324)	Otwock
Poland	Szpital Kliniczny Przemienienia Panskiego UM im. K. Marcinkowskiego ( Site 1311)	Poznan
Poland	Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu ( Site 1305)	Torun
Poland	Centrum Medyczne Onkologii I Hipertermii ( Site 1321)	Warszawa
Poland	Wojskowy Instytut Medyczny Centralny Szpital Medyczny MON ( Site 1300)	Warszawa
Poland	Mazowiecki Szpital Onkologiczny ( Site 1316)	Wieliszew	Mazowieckie
Russian Federation	Ivanovo Regional Oncology Dispensary ( Site 1204)	Ivanovo
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1210)	Krasnoyarsk
Russian Federation	N.N. Blokhin NMRCO ( Site 1206)	Moscow
Russian Federation	National Medical Research Radiology Centre ( Site 1200)	Moscow
Russian Federation	Russian Scientific Center of Roentgenoradiology ( Site 1201)	Moscow
Russian Federation	Bayandin Murmansk Regional Clinical Hospital ( Site 1214)	Murmansk
Russian Federation	Omsk Clinical Oncology Dispensary ( Site 1209)	Omsk
Russian Federation	Russian Scientific Center of Radiology and Surgical Technologies ( Site 1205)	Saint Petersburg
Russian Federation	Tomsk Scientific Research Institute of Oncology ( Site 1208)	Tomsk
Russian Federation	Clinical Hospital Bashkirsky Medical State University ( Site 1202)	Ufa
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1217)	Ufa
Spain	Hospital Universitario Infanta Cristina ( Site 1805)	Badajoz
Spain	Hospital de la Santa Creu i Sant Pau ( Site 1807)	Barcelona
Spain	Hospital de Girona Dr. Josep Trueta ( Site 1806)	Girona
Spain	Hospital Universitario Gregorio Maranon ( Site 1801)	Madrid
Spain	Hospital Universitario Ramon y Cajal ( Site 1800)	Madrid
Spain	Hospital Universitario Virgen de la Victoria ( Site 1808)	Malaga
Spain	Clinica Universitaria de Navarra ( Site 1803)	Pamplona
Spain	Hospital Universitario y Politecnico La Fe de Valencia ( Site 1809)	Valencia
Spain	Instituto Valenciano de Oncologia ( Site 1804)	Valencia
Taiwan	China Medical University Hospital ( Site 0200)	Taichung
Taiwan	Taichung Veterans General Hospital ( Site 0204)	Taichung
Taiwan	National Taiwan University Hospital ( Site 0202)	Taipei
Taiwan	Taipei Veterans General Hospital ( Site 0201)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0203)	Taoyuan
United Kingdom	Western General Hospital ( Site 1600)	Edinburgh
United Kingdom	The Beatson West of Scotland Cancer Centre ( Site 1605)	Glasgow
United Kingdom	Charing Cross Hospital ( Site 1607)	London
United Kingdom	Royal Free Hospital ( Site 1609)	London
United Kingdom	St George s Healthcare Trust ( Site 1608)	London
United Kingdom	The Christie NHS Foundation Trust ( Site 1602)	Manchester
United Kingdom	The James Cook University Hospital ( Site 1606)	Middlesbrough
United Kingdom	North Staffordshire Hospital in Stoke-on-Trent ( Site 1601)	Stoke-On-Trent	Staffordshire
United States	University of New Mexico Cancer Center ( Site 0043)	Albuquerque	New Mexico
United States	McFarland Clinic ( Site 0025)	Ames	Iowa
United States	University of Michigan ( Site 0045)	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Center ( Site 8010)	Aurora	Colorado
United States	Texas Oncology-Austin Central ( Site 8003)	Austin	Texas
United States	Weinberg Cancer Institute at Franklin Square ( Site 0046)	Baltimore	Maryland
United States	St. Vincent Healthcare Frontier Cancer Center ( Site 0008)	Billings	Montana
United States	Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0035)	Boca Raton	Florida
United States	Beth Israel Deaconess Medical Ctr. ( Site 0044)	Boston	Massachusetts
United States	Dana-Farber Cancer Institute (Boston) ( Site 0007)	Boston	Massachusetts
United States	Manatee Medical Research Institute ( Site 0039)	Bradenton	Florida
United States	Montefiore Medical Center ( Site 0009)	Bronx	New York
United States	Charleston Hematology Oncology Associates PA ( Site 8000)	Charleston	South Carolina
United States	Medical University of South Carolina ( Site 0033)	Charleston	South Carolina
United States	Oncology Hematology Care, Inc. ( Site 8008)	Cincinnati	Ohio
United States	Baylor Sammons Cancer Center/ Texas Oncology ( Site 8019)	Dallas	Texas
United States	UT Southwestern Medical Center ( Site 0003)	Dallas	Texas
United States	Texas Oncology-Denton South ( Site 8016)	Denton	Texas
United States	Henry Ford Hospital ( Site 0032)	Detroit	Michigan
United States	Karmanos Cancer Institute ( Site 0013)	Detroit	Michigan
United States	Duke University ( Site 0037)	Durham	North Carolina
United States	St. Luke's University Health Network ( Site 0042)	Easton	Pennsylvania
United States	Fairview Southdale Medical Oncology Clinic ( Site 0041)	Edina	Minnesota
United States	Providence Regional Cancer Partnership ( Site 0016)	Everett	Washington
United States	MD Anderson Cancer Center ( Site 0065)	Houston	Texas
United States	Texas Oncology-Memorial City ( Site 8015)	Houston	Texas
United States	UTHealth/Memorial Hermann Cancer Center ( Site 0001)	Houston	Texas
United States	University of Iowa Hospital and Clinics ( Site 0031)	Iowa City	Iowa
United States	Comprehensive Cancer Centers of Nevada ( Site 8013)	Las Vegas	Nevada
United States	USC Norris Comprehensive Cancer Center ( Site 0038)	Los Angeles	California
United States	University of Wisconsin Carbone Cancer Center ( Site 0019)	Madison	Wisconsin
United States	Northwest Georgia Oncology Centers PC ( Site 0014)	Marietta	Georgia
United States	Minnesota Oncology Specialist, PA ( Site 8002)	Minneapolis	Minnesota
United States	Urology Associates [Nashville, TN] ( Site 0063)	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey ( Site 0059)	New Brunswick	New Jersey
United States	University Medical Center New Orleans ( Site 0053)	New Orleans	Louisiana
United States	Illinois Cancer Specialists ( Site 8001)	Niles	Illinois
United States	Virginia Oncology Associates ( Site 8011)	Norfolk	Virginia
United States	Nebraska Cancer Specialists ( Site 0012)	Omaha	Nebraska
United States	Texas Oncology- Paris ( Site 8004)	Paris	Texas
United States	Woodlands Medical Specialists, PA ( Site 8021)	Pensacola	Florida
United States	Abramson Cancer Center ( Site 0010)	Philadelphia	Pennsylvania
United States	Arizona Oncology Associates, PC- HAL ( Site 8018)	Phoenix	Arizona
United States	Maryland Oncology Hematology, P.A. ( Site 8020)	Rockville	Maryland
United States	Quest Research Institute ( Site 0036)	Royal Oak	Michigan
United States	Park Nicollet Frauenshuh Cancer Center ( Site 0020)	Saint Louis Park	Minnesota
United States	IHO Corporation- Utah Cancer Specialists ( Site 0055)	Salt Lake City	Utah
United States	CTRC at The University of Texas Health Science Center at San Antonio ( Site 0026)	San Antonio	Texas
United States	UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0056)	San Francisco	California
United States	Sansum Clinic Research ( Site 8014)	Santa Barbara	California
United States	SCCA/UW ( Site 0029)	Seattle	Washington
United States	Avera Cancer Institute ( Site 0023)	Sioux Falls	South Dakota
United States	Cancer Care Northwest ( Site 0021)	Spokane	Washington
United States	Medical Oncology Associates (Summit Cancer Centers) ( Site 0005)	Spokane	Washington
United States	Stanford Cancer Center ( Site 0028)	Stanford	California
United States	Northwest Medical Specialties, PLLC ( Site 0034)	Tacoma	Washington
United States	Northwest Cancer Specialists, P.C. ( Site 8006)	Tigard	Oregon
United States	Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0052)	Tulsa	Oklahoma
United States	Texas Oncology-Tyler ( Site 8005)	Tyler	Texas
United States	Texas Oncology-Waco ( Site 8012)	Waco	Texas
United States	Georgetown University Medical Center ( Site 0002)	Washington	District of Columbia
United States	Yakima Valley Memorial Hospital North Star Lodge ( Site 8017)	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Brazil,  Canada,  Chile,  Colombia,  Czechia,  Finland,  France,  Germany,  Ireland,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free Survival (DFS) as Assessed by the Investigator	DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by metastasis status (M0 versus M1 no evidence of disease (NED) by investigator) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 versus 1), United States (US) participant (Yes versus No) within M0 group by investigator was used to report hazard ratio (HR) and 95% confidence intervals (CIs).	Up to approximately 42 months (database cutoff date 14 Dec 2020)
Secondary	Overall Survival (OS)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 72 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. Participants are monitored for the occurrence of nonserious AEs for up to 30 days after last dose of study treatment and of serious AEs for up to 90 days after last dose of study treatment. The number of participants who experience an AE will be assessed.	Nonserious AEs: Up to 30 days after last dose of study treatment (Up to approximately 13 months); Serious AEs: Up to 90 days after last dose of study treatment (Up to approximately 15 months)
Secondary	Number of Participants Who Discontinued Study Drug Due to an AE	An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study treatment, whether or not considered related to the use of study treatment. The number of participants who discontinue study treatment due to an AE will be assessed.	Up to approximately 12 months
Secondary	First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator	DRSS1 is defined as the time from randomization to the first documented local recurrence of RCC as assessed by the investigator. For DRSS1, only local recurrence is counted as an event.	Up to approximately 72 months
Secondary	Second Disease Recurrence-Specific Survival (DRSS2) as Assessed by the Investigator	DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or occurrence of distant kidney cancer metastasis(es) with visceral lesion, whichever occurs first, as assessed by the investigator.	Up to approximately 72 months
Secondary	Event-Free Survival (EFS) as Assessed by the Blinded Independent Central Review (BICR)	EFS is defined as time from randomization to the first documented local recurrence or occurrence of distant kidney cancer metastasis(es) among participants which by BICR were considered disease-free at baseline (M0/M1 NED); or disease progression among participants which by BICR were considered to have baseline disease (M1), or death due to any cause, whichever occurs first.	Up to approximately 72 months
Secondary	DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator	DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, or occurrence of distant kidney cancer metastasis(es), or death due to any cause, whichever occurs first. The PD-L1 expression status is based on combined positive score (CPS). If CPS is = 1, PD-L1 expression status is positive and if the CPS is <1, PD-L1 expression status is negative.	Up to approximately 72 months
Secondary	OS According to Participant PD-L1 Expression Status (Positive, Negative)	OS is defined as the time from randomization to death due to any cause. The PD-L1 expression status is based on combined positive score (CPS). If CPS is = 1, PD-L1 expression status is positive and if the CPS is <1, PD-L1 expression status is negative.	Up to approximately 72 months
Secondary	Change From Baseline in the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score	The QLQ-C30 quality of life (QOL) questionnaire contains 5 functioning scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, nausea and vomiting, and pain) and single symptom items (dyspnoea, loss of appetite, insomnia, constipation and diarrhoea) and perceived financial impact of the disease. Items are scored on a 4-point scale (1=not at all, 2=a little, 3= quite a bit, 4=very much). The QLQC30 also contains 2 global health status scales that use 7-point scale scoring (1=very poor and 7=excellent). The change from baseline in the 2-item global health status/QOL life scale (range: 2-14) will be presented, with a higher score representing a higher QOL.	Baseline and Week 52
Secondary	Change From Baseline in the Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score	The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer over the previous 7 days. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. The change from baseline in the FKSI-DRS index score will be presented.	Baseline and Week 52

External Links

•   Merck Clinical Trials Information
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