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)

• ClinicalTrials.gov Identifier: NCT03142334
• Recruitment Status: Active, not recruiting
• First Posted: May 5, 2017
• Last Update Posted: September 25, 2019
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Biological: Pembrolizumab; Drug: Placebo (saline solution)	Phase 3

Detailed 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 950 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase III, 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)
• Actual Study Start Date: June 9, 2017
• Estimated Primary Completion Date: November 12, 2022
• Estimated Study Completion Date: December 28, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Pembrolizumab; Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 17 cycles.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475; KEYTRUDA®
Placebo Comparator: Placebo; Participants receive placebo (saline solution) via IV infusion on Day 1 of each 3-week cycle for up to 17 cycles.	Drug: Placebo (saline solution); IV infusion; Other Name: saline solution

Outcome Measures

Primary Outcome Measures :

1. Disease-free Survival (DFS) as Assessed by the Investigator [ Time Frame: Up to approximately 72 months ]
   DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first.

Secondary Outcome Measures :

1. Overall Survival (OS) [ Time Frame: Up to approximately 72 months ]
   OS is defined as the time from randomization to death due to any cause.
2. Adverse Events (AEs) [ Time Frame: 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) ]
   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.
3. Study Treatment Discontinuations Due to an AE [ Time Frame: Up to approximately 12 months ]
   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.
4. First Local Disease Recurrence-specific Survival (DRSS1) as Assessed by the Investigator [ Time Frame: Up to approximately 72 months ]
   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.
5. First Local Recurrence with Visceral Lesion or Distant Metastasis with Visceral Lesion or Secondary Systemic Malignancy with Visceral Lesion (DRSS2) as Assessed by the Investigator [ Time Frame: Up to approximately 72 months ]
   DRSS2 is defined as the time from randomization to the first documented local recurrence with visceral lesion or distant metastasis with visceral lesion or secondary systemic malignancy with visceral lesion, whichever occurs first, as assessed by the investigator. For DRSS2, only disease recurrence with visceral lesion is counted as an event.
6. DFS According to Participant Programmed Cell Death-Ligand 1 (PD-L1) Expression Status (Positive, Negative) as Assessed by the Investigator [ Time Frame: Up to approximately 72 months ]
   DFS, as assessed by the investigator, is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first.
7. OS According to Participant PD-L1 Expression Status (Positive, Negative) [ Time Frame: Up to approximately 72 months ]
   OS is defined as the time from randomization to death due to any cause.
8. European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) Total Score [ Time Frame: Baseline and Cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 day follow up, and annually during post-treatment follow up. Each cycle is 3 weeks long. (Up to approximately 72 months) ]
   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.
9. Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease Related Symptoms (FKSI-DRS) Index Score [ Time Frame: Baseline and Cycles 1, 5, 9, 13, and 17, treatment discontinuation, 30 day follow up, and annually during post-treatment follow up. Each cycle is 3 weeks long. (Up to approximately 72 months) ]
   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.

Other Outcome Measures:

1. Plasma Clearance (CL) of Pembrolizumab [ Time Frame: Cycles 1 and 2: Pre-dose and 0.5 hours after end of infusion; Cycles 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months) ]
   CL is the volume of plasma from which a substance is completely removed per unit time.
2. Volume of Distribution (VD) of Pembrolizumab [ Time Frame: Cycles 1 and 2: Pre-dose and 0.5 hours after end of infusion; Cycles 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months) ]
   The VD of a drug represents the degree to which a drug is distributed in body tissue rather than the plasma. VD is directly correlated with the amount of drug distributed into tissue; a higher VD indicates a greater amount of tissue distribution.
3. Development of Anti-pembrolizumab Antibodies [ Time Frame: Cycles 1, 3, 5, 13 and 17: Pre-dose; and 30 days after study treatment discontinuation. Each cycle is 3 weeks long. (Up to approximately 13 months) ]
   The number of participants who develop serum anti-pembrolizumab antibodies will be presented.

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 histologically confirmed diagnosis of 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 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-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.

Contacts and Locations

Locations

United States, Arizona

Arizona Oncology Associates, PC- HAL ( Site 8018)

Phoenix, Arizona, United States, 85016

United States, California

USC Norris Comprehensive Cancer Center ( Site 0038)

Los Angeles, California, United States, 90033

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0056)

San Francisco, California, United States, 94158

Sansum Clinic Research ( Site 8014)

Santa Barbara, California, United States, 93105

Stanford Cancer Center ( Site 0028)

Stanford, California, United States, 94305

United States, Colorado

Rocky Mountain Cancer Center ( Site 8010)

Aurora, Colorado, United States, 80012

United States, District of Columbia

Georgetown University Medical Center ( Site 0002)

Washington, District of Columbia, United States, 20007

United States, Florida

Boca Raton Regional Hospital- Lynn Cancer Institute ( Site 0035)

Boca Raton, Florida, United States, 33486

Manatee Medical Research Institute ( Site 0039)

Bradenton, Florida, United States, 34205

Woodlands Medical Specialists, PA ( Site 8021)

Pensacola, Florida, United States, 32503

United States, Georgia

Northwest Georgia Oncology Centers PC ( Site 0014)

Marietta, Georgia, United States, 30060

United States, Illinois

Illinois Cancer Specialists ( Site 8001)

Niles, Illinois, United States, 60714

United States, Iowa

McFarland Clinic ( Site 0025)

Ames, Iowa, United States, 50010-3014

University of Iowa Hospital and Clinics ( Site 0031)

Iowa City, Iowa, United States, 52242

United States, Louisiana

University Medical Center New Orleans ( Site 0053)

New Orleans, Louisiana, United States, 70112

United States, Maryland

Weinberg Cancer Institute at Franklin Square ( Site 0046)

Baltimore, Maryland, United States, 21237

Maryland Oncology Hematology, P.A. ( Site 8020)

Rockville, Maryland, United States, 20850

United States, Massachusetts

Beth Israel Deaconess Medical Ctr. ( Site 0044)

Boston, Massachusetts, United States, 02215

Dana-Farber Cancer Institute (Boston) ( Site 0007)

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan ( Site 0045)

Ann Arbor, Michigan, United States, 48109

Karmanos Cancer Institute ( Site 0013)

Detroit, Michigan, United States, 48201

Henry Ford Hospital ( Site 0032)

Detroit, Michigan, United States, 48202

Quest Research Institute ( Site 0036)

Royal Oak, Michigan, United States, 48073

United States, Minnesota

Fairview Southdale Medical Oncology Clinic ( Site 0041)

Edina, Minnesota, United States, 55435

Minnesota Oncology Specialist, PA ( Site 8002)

Minneapolis, Minnesota, United States, 55404

Park Nicollet Frauenshuh Cancer Center ( Site 0020)

Saint Louis Park, Minnesota, United States, 55426

United States, Montana

St. Vincent Healthcare Frontier Cancer Center ( Site 0008)

Billings, Montana, United States, 59102

United States, Nebraska

Nebraska Cancer Specialists ( Site 0012)

Omaha, Nebraska, United States, 68130

United States, Nevada

Comprehensive Cancer Centers of Nevada ( Site 8013)

Las Vegas, Nevada, United States, 89148

United States, New Jersey

Rutgers Cancer Institute of New Jersey ( Site 0059)

New Brunswick, New Jersey, United States, 08903

United States, New Mexico

University of New Mexico Cancer Center ( Site 0043)

Albuquerque, New Mexico, United States, 87106

United States, New York

Montefiore Medical Center ( Site 0009)

Bronx, New York, United States, 10461

United States, North Carolina

Duke University ( Site 0037)

Durham, North Carolina, United States, 27710

United States, Ohio

Oncology Hematology Care, Inc. ( Site 8008)

Cincinnati, Ohio, United States, 45242

United States, Oklahoma

Oklahoma Cancer Specialists and Research Institute, LLC ( Site 0052)

Tulsa, Oklahoma, United States, 74146

United States, Oregon

Northwest Cancer Specialists, P.C. ( Site 8006)

Tigard, Oregon, United States, 97223

United States, Pennsylvania

St. Luke's University Health Network ( Site 0042)

Easton, Pennsylvania, United States, 18045

Abramson Cancer Center ( Site 0010)

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Charleston Hematology Oncology Associates PA ( Site 8000)

Charleston, South Carolina, United States, 29414

Medical University of South Carolina ( Site 0033)

Charleston, South Carolina, United States, 29425

United States, South Dakota

Avera Cancer Institute ( Site 0023)

Sioux Falls, South Dakota, United States, 57105

United States, Tennessee

Urology Associates [Nashville, TN] ( Site 0063)

Nashville, Tennessee, United States, 37209

United States, Texas

Texas Oncology-Austin Central ( Site 8003)

Austin, Texas, United States, 78731

Baylor Sammons Cancer Center/ Texas Oncology ( Site 8019)

Dallas, Texas, United States, 75246

UT Southwestern Medical Center ( Site 0003)

Dallas, Texas, United States, 75390

Texas Oncology-Denton South ( Site 8016)

Denton, Texas, United States, 76210

Texas Oncology-Memorial City ( Site 8015)

Houston, Texas, United States, 77024

MD Anderson Cancer Center ( Site 0065)

Houston, Texas, United States, 77030

UTHealth/Memorial Hermann Cancer Center ( Site 0001)

Houston, Texas, United States, 77030

Texas Oncology- Paris ( Site 8004)

Paris, Texas, United States, 75460-5004

CTRC at The University of Texas Health Science Center at San Antonio ( Site 0026)

San Antonio, Texas, United States, 78229

Texas Oncology-Tyler ( Site 8005)

Tyler, Texas, United States, 75702

Texas Oncology-Waco ( Site 8012)

Waco, Texas, United States, 76712

United States, Utah

IHO Corporation- Utah Cancer Specialists ( Site 0055)

Salt Lake City, Utah, United States, 84106

United States, Virginia

Virginia Oncology Associates ( Site 8011)

Norfolk, Virginia, United States, 23502

United States, Washington

Providence Regional Cancer Partnership ( Site 0016)

Everett, Washington, United States, 98201

SCCA/UW ( Site 0029)

Seattle, Washington, United States, 98109

Cancer Care Northwest ( Site 0021)

Spokane, Washington, United States, 99202

Medical Oncology Associates (Summit Cancer Centers) ( Site 0005)

Spokane, Washington, United States, 99208

Northwest Medical Specialties, PLLC ( Site 0034)

Tacoma, Washington, United States, 98405

Yakima Valley Memorial Hospital North Star Lodge ( Site 8017)

Yakima, Washington, United States, 98902

United States, Wisconsin

University of Wisconsin Carbone Cancer Center ( Site 0019)

Madison, Wisconsin, United States, 53792

Argentina

Centro de Investigaciones Clinicas - Clinica Viedma ( Site 1102)

Viedma, Rio Negro, Argentina, R8500ACE

Sanatorio Parque ( Site 1104)

Rosario, Santa Fe, Argentina, S2000DSV

Instituto de Investigaciones Metabolicas -I.D.I.M.- ( Site 1113)

Buenos Aires, Argentina, C1012AAR

Fundacion Favaloro ( Site 1110)

Buenos Aires, Argentina, C1093AAS

Instituto Medico Alexander Fleming ( Site 1105)

Buenos Aires, Argentina, C1426ANZ

Centro Oncologico Riojano Integral ( Site 1101)

La Rioja, Argentina, F5300COE

Centro Oncologico de Integracion Regional. COIR ( Site 1109)

Mendoza, Argentina, M5500AYB

Sanatorio Britanico ( Site 1106)

Rosario, Argentina, S2000CVB

Instituto de Oncologia de Rosario ( Site 1100)

Rosario, Argentina, S2000KZE

Centro Medico San Roque ( Site 1108)

Tucuman, Argentina, T4000IAK

Australia, New South Wales

Saint George Hospital [Kogarah, Australia] ( Site 0707)

Kogarah, New South Wales, Australia, 2217

Macquarie University Hospital ( Site 0700)

Macquarie Park, New South Wales, Australia, 2109

Australia, South Australia

Adelaide Cancer Centre ( Site 0703)

Kurralta Park, South Australia, Australia, 5037

Australia, Victoria

Bendigo Cancer Centre ( Site 0704)

Bendigo, Victoria, Australia, 3550

Box Hill Hospital ( Site 0701)

Box Hill, Victoria, Australia, 3128

Australia, Western Australia

Fiona Stanley Hospital ( Site 0702)

Murdoch, Western Australia, Australia, 6150

Australia

Ballarat Health Services ( Site 0705)

Ballarat, Australia, 3350

Brazil

Instituto de Cancer e Transplante de Curitiba ICTR ( Site 1012)

Curitiba, PR, Brazil, 80510-130

Liga Norte Riograndense Contra o Cancer ( Site 1013)

Natal, Rio Grande Do Norte, Brazil, 59075-740

Universidade de Caxias do Sul ( Site 1004)

Caxias do Sul, Rio Grande Do Sul, Brazil, 95070-560

Hospital Bruno Born ( Site 1015)

Lajeado, RS, Brazil, 95900-000

Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 1001)

Porto Alegre, RS, Brazil, 90610-000

Hospital Nossa Senhora da Conceicao ( Site 1000)

Porto Alegre, RS, Brazil, 91350-200

Fundacao Pio XII - Hospital de Cancer de Barretos ( Site 1002)

Barretos, Sao Paulo, Brazil, 14784-400

Fundacao Dr Amaral Carvalho ( Site 1005)

Jau, Sao Paulo, Brazil, 17210-120

Instituto do Cancer de Sao Paulo - ICESP ( Site 1010)

Sao Paulo, SP, Brazil, 01246-000

Casa de Saude Santa Marcelina ( Site 1006)

Sao Paulo, SP, Brazil, 08270-120

Hosp. Clinicas da Fac. de Medicina de Ribeirao Preto - USP ( Site 1016)

Ribeirao Preto, Brazil, 14048-900

COT Centro Oncologico do Triangulo Ltda ( Site 1014)

Uberlandia, Brazil, 38408-150

Canada, Manitoba

CancerCare Manitoba ( Site 0119)

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, New Brunswick

Dr. Leon Richard Oncology Centre ( Site 0106)

Moncton, New Brunswick, Canada, E1C 8X3

Canada, Ontario

William Osler Health System ( Site 0115)

Brampton, Ontario, Canada, L6R 3J7

Juravinski Cancer Centre ( Site 0117)

Hamilton, Ontario, Canada, L8V 5C2

London Regional Cancer Program - London HSC ( Site 0107)

London, Ontario, Canada, N6A 4L6

Lakeridge Health ( Site 0108)

Oshawa, Ontario, Canada, L1G 2B9

Niagara Health System - St. Catharines ( Site 0120)

St. Catharines, Ontario, Canada, L2S 0A9

Canada, Quebec

CIUSSS du Saguenay-Lac-St-Jean ( Site 0113)

Chicoutimi, Quebec, Canada, G7H 5H6

CISSS-CA Hotel Dieu de Levis ( Site 0111)

Lévis, Quebec, Canada, G6V 3Z1

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0118)

Montreal, Quebec, Canada, H1T 2M4

St-Jerome Medical Research Inc ( Site 0103)

St-Jerome, Quebec, Canada, J7Z 5T3

Canada, Saskatchewan

Allan Blair Cancer Centre ( Site 0116)

Regina, Saskatchewan, Canada, S4T 7T1

Saskatoon Cancer Centre ( Site 0105)

Saskatoon, Saskatchewan, Canada, S7N 4H4

Chile

Instituto Nacional del Cancer ( Site 0912)

Santiago, Region Metropolitana, Chile, 8380455

Centro Oncologico Antofagasta ( Site 0914)

Antofagasta, Chile, 1240000

Hospital Regional de La Serena ( Site 0907)

La Serena, Chile, 1710216

Hospital Regional Rancagua Libertador Bernardo O Higgins ( Site 0910)

Rancagua, Chile, 2820000

Health and Care Chile ( Site 0901)

Santiago, Chile, 7500006

Fundacion Arturo Lopez Perez FALP ( Site 0902)

Santiago, Chile, 7500921

Iram Cancer Research ( Site 0909)

Santiago, Chile, 7630372

Hospital Militar de Santiago ( Site 0911)

Santiago, Chile, 7850000

Pontificia Universidad Catolica de Chile ( Site 0904)

Santiago, Chile, 8330032

Hospital Clinico Universidad de Chile ( Site 0905)

Santiago, Chile, 8380456

Sociedad de Investigaciones Medicas Limitadas ( Site 0913)

Temuco, Chile, 4810469

Oncocentro ( Site 0900)

Vina del Mar, Chile, 2520598

Colombia

Hospital Pablo Tobon Uribe. ( Site 0805)

Medellin, Antioquia, Colombia, 050034

Clinica de la Costa Ltda. ( Site 0804)

Barranquilla, Atlantico, Colombia, 080020

Sociedad de Hematologia y Oncologia del Cesar ( Site 0809)

Valledupar, Cesar, Colombia, 200001

Instituto Nacional de Cancerologia E.S.E ( Site 0807)

Bogota, Cundinamarca, Colombia, 111161

Oncologos del Occidente S.A. ( Site 0800)

Pereira, Risaralda, Colombia, 661002

Fundacion CardioInfantil Instituto de Cardiologia ( Site 0803)

Bogota, Colombia, 110131

Administradora Country SA - Clinica del Country ( Site 0808)

Bogota, Colombia, 110221

Oncomedica S.A. ( Site 0801)

Monteria, Colombia, 230002

Czechia

FN Brno. ( Site 1501)

Brno, Czechia, 625 00

Nemocnice Novy Jicin a.s. Clen skupiny AGEL ( Site 1506)

Novy Jicin, Czechia, 741 01

Fakultni nemocnice Olomouc ( Site 1502)

Olomouc, Czechia, 775 20

Fakultni nemocnice Ostrava ( Site 1507)

Ostrava, Czechia, 708 52

Thomayerova nemocnice ( Site 1505)

Praha 4, Czechia, 140 59

Fakultni nemocnice v Motole ( Site 1504)

Praha 5, Czechia, 150 06

Nemocnice Na Bulovce ( Site 1503)

Praha 8, Czechia, 180 81

Finland

HYKS ( Site 2300)

Helsinki, Finland, 00290

Keski-Suomen keskussairaala ( Site 2303)

Jyvaskyla, Finland, 40620

Oulun yliopistollinen sairaala - OYS ( Site 2304)

Oulu, Finland, 90220

TAYS ( Site 2301)

Tampere, Finland, 33520

TYKS ( Site 2302)

Turku, Finland, 20521

France

ICO Centre Paul Papin ( Site 2208)

Angers, France, 49055

CHU Besancon - Hopital Jean Minjoz ( Site 2200)

Besancon, France, 25000

Hopital Saint Andre ( Site 2202)

Bordeaux, France, 33075

Hopital La Timone ( Site 2204)

Marseille, France, 13005

CHU Saint-Eloi ( Site 2203)

Montpellier, France, 34295

Centre Antoine Lacassagne ( Site 2211)

Nice, France, 06189

Hopital Europeen Georges Pompidou ( Site 2206)

Paris, France, 75908

Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 2212)

Pierre Benite, France, 69310

Centre Eugene Marquis ( Site 2209)

Rennes, France, 35042

Centre Rene Gauducheau ICO ( Site 2207)

Saint Herblain, France, 44805

Institut Claudius Regaud IUCT Oncopole ( Site 2201)

Toulouse, France, 31059

Germany

Campus Charite Mitte ( Site 2120)

Berlin, Germany, 10117

Helios Klinikum Berlin Buch ( Site 2125)

Berlin, Germany, 13125

Universitaetsklinikum Bonn ( Site 2110)

Bonn, Germany, 53127

Universitaetsklinikum der Technischen Universitaet Dresden ( Site 2113)

Dresden, Germany, 01307

Universitatsklinikum Dusseldorf ( Site 2108)

Dusseldorf, Germany, 40225

Universitaetsklinikum Erlangen. Waldkrankenhaus ( Site 2102)

Erlangen, Germany, 91054

Universitaetsklinikum Essen ( Site 2116)

Essen, Germany, 45122

Universitaetsklinikum Frankfurt ( Site 2121)

Frankfurt, Germany, 60590

Universitaetsklinikum Freiburg ( Site 2119)

Freiburg, Germany, 79106

Universitaetsklinikum Hamburg-Eppendorf ( Site 2118)

Hamburg, Germany, 20246

Universitaetsklinikum Jena. ( Site 2104)

Jena, Germany, 07747

Universitaetsklinikum Schleswig Holstein ( Site 2109)

Luebeck, Germany, 23538

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 2111)

Mainz, Germany, 55131

Studienpraxis Urologie ( Site 2115)

Nuertingen, Germany, 72622

Krankenhaus der Barmherzigen Brueder Trier ( Site 2117)

Trier, Germany, 54292

Universitaetsklinikum Tuebingen ( Site 2100)

Tuebingen, Germany, 72076

Ireland

Beaumont Hospital ( Site 1611)

Dublin, Ireland, D04 Y8V0

St Vincents University Hospital ( Site 1610)

Dublin, Ireland, D04 Y8V0

University Hospital Waterford ( Site 1614)

Waterford, Ireland, X91 ER8E

Italy

Ospedale San Luigi Gonzaga ( Site 2010)

Orbassano, Torino, Italy, 10043

Medical Oncology Ospedale San Donato ( Site 2004)

Arezzo, Italy, 52100

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 2012)

Meldola, Italy, 47014

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2005)

Milano, Italy, 20133

Istituto Europeo di Oncologia ( Site 2000)

Milano, Italy, 20141

Azienda Ospedaliero Universitaria di Modena Policlinico ( Site 2006)

Modena, Italy, 41125

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 2003)

Napoli, Italy, 80131

Istituto Nazionale Tumori Regina Elena ( Site 2009)

Roma, Italy, 00144

Japan

Nagoya University Hospital ( Site 0431)

Nagoya, Aichi, Japan, 466-8560

Sapporo Medical University Hospital ( Site 0424)

Sapporo, Hokkaido, Japan, 060-8543

Kagawa University Hospital ( Site 0419)

Kita-gun, Kagawa, Japan, 761-0793

Japan Community Health care Organization Sendai Hospital ( Site 0430)

Sendai, Miyagi, Japan, 981-8501

Nara Medical University Hospital ( Site 0416)

Kashihara, Nara, Japan, 634-8522

Kindai University Hospital ( Site 0411)

Osakasayama, Osaka, Japan, 589-8511

Osaka Rosai Hospital ( Site 0418)

Sakai, Osaka, Japan, 591-8025

Saitama Medical University International Medical Center ( Site 0404)

Hidaka, Saitama, Japan, 350-1298

Yamaguchi University Hospital ( Site 0406)

Ube, Yamaguchi, Japan, 755-8505

Akita University Hospital ( Site 0433)

Akita, Japan, 010-8543

Harasanshin Hospital ( Site 0402)

Fukuoka, Japan, 812-0033

Kyushu University Hospital ( Site 0413)

Fukuoka, Japan, 812-8582

Kumamoto University Hospital ( Site 0434)

Kumamoto, Japan, 860-8556

Nagano Municipal Hospital ( Site 0429)

Nagano, Japan, 381-8551

Niigata University Medical & Dental Hospital ( Site 0421)

Niigata, Japan, 951-8520

Osaka International Cancer Institute ( Site 0401)

Osaka, Japan, 541-8567

Osaka City University Hospital ( Site 0428)

Osaka, Japan, 545-8586

Toranomon Hospital ( Site 0426)

Tokyo, Japan, 105-8470

Nippon Medical School Hospital ( Site 0400)

Tokyo, Japan, 113-8603

Keio University Hospital ( Site 0407)

Tokyo, Japan, 160-8582

Toyama University Hospital ( Site 0432)

Toyama, Japan, 930-0194

Korea, Republic of

National Cancer Center ( Site 0304)

Goyang-si, Gyeonggi-do, Korea, Republic of, 10408

Seoul National University Hospital ( Site 0302)

Seoul, Korea, Republic of, 03080

Severance Hospital Yonsei University Health System ( Site 0303)

Seoul, Korea, Republic of, 03722

Asan Medical Center ( Site 0300)

Seoul, Korea, Republic of, 05505

Samsung Medical Center ( Site 0301)

Seoul, Korea, Republic of, 06351

Netherlands

Amphia Ziekenhuis Breda ( Site 1901)

Breda, Netherlands, 4819 EV

Maastricht Universitair Medisch Centrum - MUMC ( Site 1902)

Maastricht, Netherlands, 6229 HX

Franciscus Gasthuis ( Site 1903)

Rotterdam, Netherlands, 3045 PM

Poland

Mazowiecki Szpital Onkologiczny ( Site 1316)

Wieliszew, Mazowieckie, Poland, 05-135

Szpital Specjalistyczny w Koscierzynie Sp. z o.o. ( Site 1322)

Koscierzyna, Pomorskie, Poland, 83-400

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny ( Site 1309)

Brzozow, Poland, 36-200

Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1307)

Bytom, Poland, 41-902

Wojewodzkie Centrum Onkologii Copernicus ( Site 1304)

Gdansk, Poland, 80-219

Szpital Morski im. PCK Szpitale Wojewodzkie w Gdyni Sp. z o.o. ( Site 1302)

Gdynia, Poland, 81-519

Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1323)

Gliwice, Poland, 44-101

Przychodnia Lekarska Komed ( Site 1306)

Konin, Poland, 62-500

Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1310)

Krakow, Poland, 31-115

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1315)

Lublin, Poland, 20-090

Europejskie Centrum Zdrowia Otwock Szpital im. Fryderyka Chopina ( Site 1324)

Otwock, Poland, 05-400

Szpital Kliniczny Przemienienia Panskiego UM im. K. Marcinkowskiego ( Site 1311)

Poznan, Poland, 60-569

Wojewodzki Szpital Zespolony im. L. Rydygiera w Toruniu ( Site 1305)

Torun, Poland, 87-100

Centrum Medyczne Onkologii I Hipertermii ( Site 1321)

Warszawa, Poland, 02-793

Wojskowy Instytut Medyczny Centralny Szpital Medyczny MON ( Site 1300)

Warszawa, Poland, 04-141

Russian Federation

Ivanovo Regional Oncology Dispensary ( Site 1204)

Ivanovo, Russian Federation, 153040

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1210)

Krasnoyarsk, Russian Federation, 660133

N.N. Blokhin NMRCO ( Site 1206)

Moscow, Russian Federation, 115478

Russian Scientific Center of Roentgenoradiology ( Site 1201)

Moscow, Russian Federation, 117997

National Medical Research Radiology Centre ( Site 1200)

Moscow, Russian Federation, 125284

Bayandin Murmansk Regional Clinical Hospital ( Site 1214)

Murmansk, Russian Federation, 183057

Omsk Clinical Oncology Dispensary ( Site 1209)

Omsk, Russian Federation, 644013

Russian Scientific Center of Radiology and Surgical Technologies ( Site 1205)

Saint Petersburg, Russian Federation, 197758

Tomsk Scientific Research Institute of Oncology ( Site 1208)

Tomsk, Russian Federation, 634028

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1217)

Ufa, Russian Federation, 450054

Clinical Hospital Bashkirsky Medical State University ( Site 1202)

Ufa, Russian Federation, 450083

Spain

Hospital Universitario Infanta Cristina ( Site 1805)

Badajoz, Spain, 06080

Hospital de la Santa Creu i Sant Pau ( Site 1807)

Barcelona, Spain, 08026

Hospital de Girona Dr. Josep Trueta ( Site 1806)

Girona, Spain, 17007

Hospital Universitario Gregorio Maranon ( Site 1801)

Madrid, Spain, 28007

Hospital Universitario Ramon y Cajal ( Site 1800)

Madrid, Spain, 28034

Hospital Universitario Virgen de la Victoria ( Site 1808)

Malaga, Spain, 29010

Clinica Universitaria de Navarra ( Site 1803)

Pamplona, Spain, 31008

Instituto Valenciano de Oncologia ( Site 1804)

Valencia, Spain, 46009

Hospital Universitario y Politecnico La Fe de Valencia ( Site 1809)

Valencia, Spain, 46026

Taiwan

China Medical University Hospital ( Site 0200)

Taichung, Taiwan, 40447

Taichung Veterans General Hospital ( Site 0204)

Taichung, Taiwan, 407

National Taiwan University Hospital ( Site 0202)

Taipei, Taiwan, 10002

Taipei Veterans General Hospital ( Site 0201)

Taipei, Taiwan, 112

Chang Gung Medical Foundation. Linkou ( Site 0203)

Taoyuan, Taiwan, 333

United Kingdom

North Staffordshire Hospital in Stoke-on-Trent ( Site 1601)

Stoke-On-Trent, Staffordshire, United Kingdom, ST4 6QG

Western General Hospital ( Site 1600)

Edinburgh, United Kingdom, EH4 2XU

The Beatson West of Scotland Cancer Centre ( Site 1605)

Glasgow, United Kingdom, G12 0YN

Royal Free Hospital ( Site 1609)

London, United Kingdom, NW3 2QG

St George s Healthcare Trust ( Site 1608)

London, United Kingdom, SW17 0QT

Charing Cross Hospital ( Site 1607)

London, United Kingdom, W6 8RF

The Christie NHS Foundation Trust ( Site 1602)

Manchester, United Kingdom, M20 4BX

The James Cook University Hospital ( Site 1606)

Middlesbrough, United Kingdom, TS4 3BW

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme Corp.

More Information

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT03142334
• Other Study ID Numbers: 3475-564; 2016-004351-75 ( EudraCT Number ); 173704 ( Registry Identifier: JAPAC-CTI ); MK-3475-564 ( Other Identifier: Merck ); KEYNOTE-564 ( Other Identifier: Merck )
• First Posted: May 5, 2017
• Last Update Posted: September 25, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• 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 Corp.:

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1); Adjuvant

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Pembrolizumab; Pharmaceutical Solutions; Antineoplastic Agents, Immunological; Antineoplastic Agents