Efficacy and Safety of Pembrolizumab (MK-3475) Plus Enzalutamide Plus Androgen Deprivation Therapy (ADT) Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (MK-3475-991/KEYNOTE-991)

Recruitment Status
COMPLETED - HAS RESULTS
(See Contacts and Locations)Verified March 2026 by Merck Sharp & Dohme LLC
Sponsor
Merck Sharp & Dohme LLC
Information Provided by (Responsible Party)
Merck Sharp & Dohme LLC
Clinicaltrials.gov Identifier
NCT04191096
Other Study ID Numbers:
3475-991
First Submitted
December 4, 2019
First Posted
December 8, 2019
Results First Posted
October 10, 2023
Last Update Posted
April 28, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Metastatic Hormone-Sensitive Prostate Cancer
Biological: PembrolizumabDrug: Enzalutamide

Study Design

Study TypeInterventional
Actual Enrollment1251 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingDouble
Primary PurposeTreatment
Official TitleA Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) Plus Enzalutamide Plus ADT Versus Placebo Plus Enzalutamide Plus ADT in Participants With Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) (KEYNOTE-991)
Study Start DateFebruary 11, 2020
Actual Primary Completion DateOctober 30, 2022
Actual Study Completion DateApril 7, 2026

Groups and Cohorts

Group/CohortIntervention/Treatment
Pembrolizumab + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive 200 mg pembrolizumab IV every 3 weeks (Q3W) for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a luteinizing-hormone releasing hormone (LHRH) agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Biological: Pembrolizumab
Pembrolizumab is administered as an IV infusion at 200 mg on Day 1 of each 21-day cycle for up to 35 cycles.
Placebo + Enzalutamide + ADT
Starting on Day 1 of each 21-day cycle, participants receive placebo IV Q3W for up to 35 cycles (approximately 2 years), plus 160 mg enzalutamide taken orally once daily, while maintaining continuous ADT with a LHRH agonist or antagonist during study treatment. Participants will continue to receive enzalutamide and ADT until criteria for discontinuation are met.
Drug: Enzalutamide
Enzalutamide is administered orally as capsules/tablets at a dosage of 160 mg daily. Enzalutamide is administered continuously until criteria for discontinuation are met.

Outcome Measures

Primary Outcome Measures
  1. Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
    rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per modified RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment.
  2. Overall Survival (OS)
    OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Secondary Outcome Measures
  1. Time to Initiation of the First Subsequent Anti-cancer Therapy or Death (TFST)
    TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product limit (Kaplan-Meier) method for censored data. Participants without documented event at time of analysis will be censored at the date of last known time to have not received subsequent new anti-cancer therapy.
  2. Time to First Symptomatic Skeletal-related Event (TTSSRE)
    TTSSRE was the time from randomization to the first symptomatic skeletal-related event defined as: use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms, occurrence of new symptomatic pathologic bone fracture (vertebral or nonvertebral), occurrence of spinal cord compression, or tumor-related orthopedic surgical intervention, whichever occurs first. The TTSSRE was calculated using the Kaplan-Meier method for censored data. Participants without symptomatic skeletal-related events were censored at the last evaluable assessment.
  3. Time to Prostate-specific Antigen (PSA) Progression
    Time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there is PSA decline from baseline, or 2) ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there is no PSA decline from baseline. Time to PSA was calculated using Kaplan-Meier method for censored data. Participants without PSA progression were censored at the last PSA date.
  4. Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of PCWG-Modified RECIST 1.1 as Assessed by BICR
    The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression was defined as ≥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 ≥5 mm. The appearance of one or more new lesions was also considered progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment.
  5. Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item #3 ("Worst Pain in 24 Hours") and Opiate Use
    TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF. Pain progression was defined as: 1) For participants asymptomatic at baseline: a \>2-point change from baseline in the average BPI-SF item 3 score at 2 consecutive visits or initiation of opioid use for pain 2) For participants symptomatic at baseline (average BPI-SF Item 3 score \>0 and/or currently taking opioids; a \>2-point change from baseline in the average BPI-SF Item 3 score and the average worst pain score \>4 and no decrease in average opioid use. TTPP was calculated using the Kaplan-Meier method for censored data. Participants who had \> 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment.
  6. Time From Randomization to Disease Progression as Determined by Investigator Assessment After Next-line of Therapy or Death From Any Cause, Whichever Occurs First (PFS2)
    PFS2 was defined as the time from randomization to disease progression as determined by investigator assessment of radiological or clinical progression after next-line of therapy or death from any cause, whichever occurs first.
  7. Prostate-specific Antigen (PSA) Response Rate
    PSA response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by \>50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed \>3 weeks from the original response.
  8. Prostate-specific Antigen (PSA) Undetectable
    PSA undetectable rate was defined as the percentage of participants with detectable PSA (\> 0.2 ng/mL) at baseline, which becomes undetectable (\< 0.2 ng/mL) during study treatment.
  9. Objective Response Rate (ORR) Per PCWG-Modified RECIST 1.1 as Assessed by BICR
    ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on base scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable \[NE\], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG).
  10. Duration of Response (DOR) Per PCWG- Modified RECIST 1.1 as Assessed by BICR
    DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 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 demonstrate an absolute increase of a least 5 mm. PD per PCWG was the appearance of \>2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for \>6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data.
  11. Number of Participants Who Experience an Adverse Event (AE)
    An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE could therefore have been any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Participants who experienced an AE will be reported for each arm.
  12. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
    An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported for each arm.

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyMale
Accepts Healthy VolunteersNo
Inclusion Criteria
Male participants with histologically- or cytologically-confirmed adenocarcinoma of the prostate without small cell histology
Has metastatic disease assessed by investigator and verified by BICR by either ≥2 bone lesions on bone scan and/or visceral disease by computed tomography/magnetic resonance imaging (CT/MRI)
Willing to maintain continuous Androgen Deprivation Therapy (ADT) with a luteinizing-hormone releasing hormone (LHRH) agonists or antagonists during study treatment or have a history of bilateral orchiectomy
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days of randomization
Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses prior to randomization
Has adequate organ function
Has provided newly obtained core or excisional biopsy (obtained within 12 months of screening) from soft tissue not previously irradiated (samples from tumors progressing in a prior site of radiation are allowed). Participants with bone only or bone predominant disease may provide a bone biopsy sample
Male participants must agree to the following during the intervention period and for at least 120 days after the last dose of study intervention: Refrain from donating sperm PLUS either be abstinent from heterosexual intercourse and agree to remain abstinent OR agree to use contraception, unless confirmed to be azoospermic
Male participants must agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
Exclusion Criteria
Has a known additional malignancy that is progressing or has required active treatment in the last 3 years
Has an active autoimmune disease that has required systemic treatment in past 2 years
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
Has undergone major surgery including local prostate intervention (excluding prostate biopsy) within 28 days prior to randomization and not recovered adequately from the toxicities and/or complications
Has a gastrointestinal disorder affecting absorption or is unable to swallow tablets/capsules
Has an active infection (including tuberculosis) requiring systemic therapy
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has known active human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
Has known or suspected central nervous system (CNS) metastases and/or carcinomatous meningitis
Has a history of seizure or any condition that may predispose to seizure
Has a history of loss of consciousness within 12 months of screening
Has had myocardial infarction or uncontrolled angina within 6 months prior to randomization, or has New York Heart Association class III or IV congestive heart failure or a history of New York Heart Association class III or IV congestive heart failure
Has hypotension (systolic blood pressure \<86 millimeters of mercury \[mmHg\]) or uncontrolled hypertension (systolic blood pressure \>170 mmHg or diastolic blood pressure \>105 mmHg) at the screening visit
Has a history of clinically significant ventricular arrhythmias
Has hypersensitivity to pembrolizumab and/or enzalutamide and/or any of their excipients
Has received prior ADT as neoadjuvant/adjuvant therapy for non-metastatic prostate cancer for \>39 months in duration or within 9 months prior to randomization or with evidence of disease progression while receiving ADT
Has had prior treatment with a next generation hormonal agent (eg, abiraterone, enzalutamide, apalutamide, darolutamide)
Has received prior therapy with an anti-programmed cell death-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 stimulatory or coinhibitory T-cell receptor
Has received a live vaccine within 30 days prior to randomization
Has a "superscan" bone scan
Has had an allogenic tissue/solid organ transplant
Is 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 any prior pharmacotherapy, radiation therapy or surgery for metastatic prostate cancer with the following exceptions: 1. Up to 3 months of ADT or orchiectomy with or without concurrent first-generation antiandrogens, if patient was not treated with docetaxel 2. May have 1 course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease if it was administered at least 4 weeks prior to randomization 3. For participants with low volume metastatic disease, may have 1 course of definitive radiotherapy if it was administered at least 4 weeks prior to randomization 4. Up to 6 cycles of docetaxel therapy with final treatment administration completed within 2 months of randomization and no evidence of disease progression. In these participants up to 6 months of ADT permitted

Contacts and Locations

Sponsors and CollaboratorsMerck Sharp & Dohme LLC
Locations
Alaska Clinical Research Center ( Site 0274) | Anchorage Alaska, United States, 99503Providence Alaska Medical Center ( Site 0276) | Anchorage Alaska, United States, 99508City of Hope Medical Center ( Site 0217) | Duarte California, United States, 91010UCLA Hematology/Oncology - Santa Monica ( Site 0241) | Los Angeles California, United States, 90404University of Colorado, Anschutz Cancer Pavilion ( Site 0236) | Aurora Colorado, United States, 80045Hartford HealthCare Medical Group ( Site 0212) | Manchester Connecticut, United States, 06042Smilow Cancer Center at Yale-New Haven ( Site 0250) | New Haven Connecticut, United States, 06510Sibley Memorial Hospital ( Site 0275) | Washington D.C. District of Columbia, United States, 20016Winship Cancer Institute of Emory University ( Site 0209) | Atlanta Georgia, United States, 30322-1013The University of Chicago ( Site 0264) | Chicago Illinois, United States, 60637Springfield Clinic [Springfield, IL] ( Site 0240) | Springfield Illinois, United States, 62702Cotton-O'Neil Cancer Center ( Site 0228) | Topeka Kansas, United States, 66606The Sidney Kimmel Comprehensive Cancer Center ( Site 0204) | Baltimore Maryland, United States, 21287St. Vincent Frontier Cancer Center-Research ( Site 0213) | Billings Montana, United States, 59102Comprehensive Cancer Centers of Nevada ( Site 0269) | Las Vegas Nevada, United States, 89169Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0270) | New York New York, United States, 10016Weill Cornell Medical College ( Site 0263) | New York New York, United States, 10065Associated Medical Professionals of NY ( Site 0251) | Syracuse New York, United States, 13210Duke University ( Site 0206) | Durham North Carolina, United States, 27710TriState Urologic Services PSC Inc. dba The Urology Group ( Site 0253) | Cincinnati Ohio, United States, 45212MidLantic Urology ( Site 0273) | Bala-Cynwyd Pennsylvania, United States, 19004Ralph H. Johnson VA Center ( Site 0256) | Charleston South Carolina, United States, 29401Carolina Urologic Research Center ( Site 0259) | Myrtle Beach South Carolina, United States, 29572Urology Associates [Nashville, TN] ( Site 0233) | Nashville Tennessee, United States, 37209Inova Health System ( Site 0205) | Fairfax Virginia, United States, 22031Urology of Virginia ( Site 0224) | Virginia Beach Virginia, United States, 23462Fred Hutchinson Cancer Center ( Site 0258) | Seattle Washington, United States, 98109Chris OBrien Lifehouse ( Site 0300) | Camperdown New South Wales, Australia, 2050Port Macquarie Base Hospital ( Site 0301) | Port Macquarie New South Wales, Australia, 2444Riverina Cancer Care Center ( Site 0302) | Wagga Wagga New South Wales, Australia, 2650Gallipoli Medical Research Ltd ( Site 0309) | Greenslopes Queensland, Australia, 4120John Flynn Hospital & Medical Centre ( Site 0308) | Tugun Queensland, Australia, 4224Box Hill Hospital ( Site 0304) | Box Hill Victoria, Australia, 3128Monash Health ( Site 0305) | Clayton Victoria, Australia, 3168Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 0306) | Melbourne Victoria, Australia, 3000Fiona Stanley Hospital ( Site 0311) | Perth Western Australia, Australia, 6150Ordensklinikum Linz GmbH Elisabethinen ( Site 0901) | Linz Upper Austria, Austria, 4020Landeskrankenhaus Salzburg - Universitatklinikum der PMU ( Site 0900) | Salzburg , Austria, 5020Krankenhaus der Barmherzigen Brüder Wien ( Site 0904) | Vienna , Austria, 1020Medizinische Universität Wien ( Site 0903) | Vienna , Austria, 1090Oncocentro Ceara ( Site 2309) | Fortaleza Ceará, Brazil, 60135-237Instituto de Cancer e Transplante de Curitiba ICTR ( Site 2306) | Curitiba Paraná, Brazil, 80510-130Hospital Sao Vicente de Paulo ( Site 2303) | Passo Fundo Rio Grande do Sul, Brazil, 99010-080Hospital de Clinicas de Porto Alegre ( Site 2304) | Porto Alegre Rio Grande do Sul, Brazil, 90035-903Clinica de Oncologia Reichow ( Site 2308) | Blumenau Santa Catarina, Brazil, 89010-340Fundacao Dr Amaral Carvalho ( Site 2302) | Jaú São Paulo, Brazil, 17210-120Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 2305) | São Paulo , Brazil, 12460-000The Ottawa Hospital ( Site 0100) | Ottawa Ontario, Canada, K1H 8L6Niagara Health System - St. Catharines ( Site 0107) | St. Catharines Ontario, Canada, L2S 0A9CISSS de la Monteregie-Centre ( Site 0105) | Greenfield Park Quebec, Canada, J4V 2H1Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0109) | Montreal Quebec, Canada, H2X 3E4CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0106) | Montreal Quebec, Canada, H3T 1M5Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0101) | Québec Quebec, Canada, G1J 1Z4Centro Investigación del Cáncer James Lind ( Site 2401) | Temuco Araucania, Chile, 4800827IC La Serena Research ( Site 2406) | La Serena Coquimbo Region, Chile, 1720430Clinica Universidad Catolica del Maule ( Site 2407) | Talca Maule Region, Chile, 3465584Clinica Alemana ( Site 2408) | Santiago Region M. de Santiago, Chile, 7650568Pontificia Universidad Catolica de Chile ( Site 2402) | Santiago Region M. de Santiago, Chile, 8330024Bradfordhill ( Site 2403) | Santiago Region M. de Santiago, Chile, 8420383Oncocentro ( Site 2400) | Viña del Mar Valparaiso, Chile, 2520598Peking University First Hospital ( Site 0800) | Beijing Beijing Municipality, China, 100034Beijing Cancer Hospital ( Site 0802) | Beijing Beijing Municipality, China, 100142Chongqing Cancer Hospital ( Site 0815) | Chongqing Chongqing Municipality, China, 400030The First Affiliated Hospital of Xiamen University ( Site 0816) | Xiamen Fujian, China, 361003The First Affiliated Hospital of Guangzhou Medical University-Urology ( Site 0837) | Guangdong Guangdong, China, 510080Sun Yat-Sen University Cancer Center ( Site 0825) | Guangzhou Guangdong, China, 510060Sun Yat Sen Memorial Hospital ( Site 0819) | Guangzhou Guangdong, China, 510220Southern Medical University Nanfang Hospital ( Site 0838) | Guangzhou Guangdong, China, 510515Harbin Medical University Cancer Hospital ( Site 0822) | Harbin Heilongjiang, China, 150081Henan Cancer Hospital ( Site 0818) | Zhengzhou Henan, China, 450008Union Hospital Tongji Medical College Huazhong University of Science and Technology ( Site 0829) | Wuhan Hubei, China, 430000Hubei Cancer Hospital ( Site 0833) | Wuhan Hubei, China, 430079Hunan Cancer Hospital ( Site 0817) | Changsha Hunan, China, 410013Nanjing Drum Tower Hospital ( Site 0811) | Nanjing Jiangsu, China, 210008The First Affiliated Hospital of Nanchang University ( Site 0821) | Nanchang Jiangxi, China, 330006The Second Affiliated Hosp of Xi'an Jiaotong Univ College of Medicine ( Site 0831) | Xi'an Shaanxi, China, 710004Renji Hospital Shanghai Jiaotong University School of Medicine ( Site 0807) | Shanghai Shanghai Municipality, China, 200127The first affiliated Hospital of Xi an Jiaotong University ( Site 0812) | Xi’an Shanxi, China, 710061Tianjin Medical University Cancer Institute & Hospital ( Site 0804) | Tianjin Tianjin Municipality, China, 3000002nd Affil Hosp of Zhejiang University College of Medicine ( Site 0808) | Hangzhou Zhejiang, China, 310009The 1st Affil Hosp of College of Medicine, Zhejiang Univ ( Site 0830) | Hangzhou Zhejiang, China, 310009Zhejiang Provincial People's Hospital ( Site 0809) | Hangzhou Zhejiang, China, 310014Ningbo First Hospital-Urology ( Site 0835) | Ningbo Zhejiang, China, 315010The First Affiliated Hospital of Wenzhou Medical University ( Site 0834) | Wenzhou Zhejiang, China, 325000Clinica de la Costa S.A.S. ( Site 2504) | Barranquilla Atlántico, Colombia, 080020Administradora Country SA - Clinica del Country ( Site 2507) | Bogotá Bogota D.C., Colombia, 110221Instituto Nacional de Cancerologia E.S.E ( Site 2506) | Bogotá Bogota D.C., Colombia, 111511Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2509) | Valledupar Cesar Department, Colombia, 200001Hemato Oncologos ( Site 2503) | Cali Valle del Cauca Department, Colombia, 760042Rigshospitalet ( Site 1005) | Copenhagen Capital Region, Denmark, 2100Herlev og Gentofte Hospital. ( Site 1004) | Herlev Capital Region, Denmark, 2730Aalborg Universitetshospital ( Site 1000) | Aalborg North Denmark, Denmark, 9000Odense Universitetshospital ( Site 1003) | Odense Region Syddanmark, Denmark, 5000Vejle Sygehus ( Site 1002) | Vejle Region Syddanmark, Denmark, 7100Keski-Suomen keskussairaala ( Site 1017) | Jyväskylä Central Finland, Finland, 40620Tampereen yliopistollinen sairaala ( Site 1022) | Tampere Pirkanmaa, Finland, 33520HYKS ( Site 1020) | Helsinki Southwest Finland, Finland, 00290TYKS T-sairaala Syopatautien pkl ( Site 1019) | Turku Southwest Finland, Finland, 20520Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1114) | Strasbourg Alsace, France, 67200Centre Georges Francois Leclerc ( Site 1112) | Dijon Cote-d Or, France, 21079CHU-Jean Minjoz ( Site 1101) | Besançon Doubs, France, 25000CHU de Brest -Site Hopital Morvan ( Site 1103) | Brest Finistere, France, 29200Institut Bergonie ( Site 1104) | Bordeaux Gironde, France, 33076Centre Bourgogne ( Site 1119) | Lille Hauts-de-France, France, 59000Hopital Foch ( Site 1105) | Suresnes Hauts-de-Seine, France, 92151C.H.R.U. de Rennes. Hopital de Pontchaillou ( Site 1117) | Rennes Ille-et-Vilaine, France, 35033Institut Jean Godinot-Clinical Research Unit ( Site 1118) | Reims Marne, France, 51100Centre D Oncologie de Gentilly ( Site 1107) | Nancy Meurthe-et-Moselle, France, 54000Centre Leon-Berard ( Site 1110) | Lyon Rhone, France, 69373Hospices Civils de Lyon Centre Hospitalier Lyon Sud ( Site 1102) | Pierre-Bénite Rhone, France, 69310Hopital Henri Mondor ( Site 1116) | Créteil Val-de-Marne, France, 94010Universitaetsklinikum Freiburg ( Site 1200) | Freiburg im Breisgau Baden-Wurttemberg, Germany, 79106Klinikum der Universitaet Muenchen - Grosshadern ( Site 1210) | Munich Bavaria, Germany, 81377Klinikum Rechts der Isar ( Site 1206) | München Bavaria, Germany, 81675Klinikum Nuernberg Nord ( Site 1213) | Nuremberg Bavaria, Germany, 90419Staedtisches Klinikum Braunschweig gGmbH ( Site 1217) | Braunschweig Lower Saxony, Germany, 38126Universitaetsklinikum der Technischen Universitaet Dresden ( Site 1204) | Dresden Saxony, Germany, 01307Universitaetsklinikum Magdeburg A.o.R. ( Site 1211) | Magdeburg Saxony-Anhalt, Germany, 39120Charite Universitaetsmedizin Berlin ( Site 1201) | Berlin , Germany, 10117Universitaetsklinikum Hamburg-Eppendorf ( Site 1212) | Hamburg , Germany, 20246St Vincents University Hospital ( Site 1300) | Dublin Dublin, Ireland, D04 T6F4Cork University Hospital ( Site 1304) | Cork , Ireland, T12 DC4ATallaght University Hospital ( Site 1301) | Dublin , Ireland, D24 NR0ABeaumont Hospital ( Site 1302) | Dublin , Ireland, Dublin 9University Hospital Limerick ( Site 1305) | Limerick , Ireland, V94 F858University Hospital Waterford ( Site 1303) | Waterford , Ireland, X91 ER8ERambam Health Care Campus-Oncology Division ( Site 1400) | Haifa , Israel, 3109601Hadassah Ein Kerem Medical Center ( Site 1404) | Jerusalem , Israel, 9112001Meir Medical Center ( Site 1401) | Kfar Saba , Israel, 4428164Rabin Medical Center ( Site 1402) | Petah Tikva , Israel, 4941492Sourasky Medical Center ( Site 1403) | Tel Aviv , Israel, 6423906Yitzhak Shamir Medical Center. ( Site 1405) | Ẕerifin , Israel, 70300Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1503) | Meldola Forli-Cesena, Italy, 47014Fondazione Policlinico Universitario A. Gemelli ( Site 1512) | Rome Lazio, Italy, 00168Istituto Clinico Humanitas Research Hospital ( Site 1500) | Rozzano Lombardy, Italy, 20089Centro Di Riferimento Oncologico ( Site 1511) | Aviano Pordenone, Italy, 33081IRCCS Giovanni Paolo II. Ospedale Oncologico ( Site 1509) | Bari , Italy, 70124Azienda Ospedaliera Cannizzaro ( Site 1501) | Catania , Italy, 95126Istituto Nazionale dei Tumori ( Site 1510) | Milan , Italy, 20133Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1508) | Naples , Italy, 80131Azienda Ospedaliera Santa Maria ( Site 1502) | Terni , Italy, 05100A.O. Verona-Ospedale Civile Maggiore Borgo-Trento ( Site 1504) | Verona , Italy, 37126Toho University Sakura Medical Center ( Site 0732) | Sakura Chiba, Japan, 285-8741Ehime University Hospital ( Site 0745) | Tōon Ehime, Japan, 791-0295Sapporo Medical University Hospital ( Site 0730) | Sapporo Hokkaido, Japan, 060-8543Kitasato University Hospital ( Site 0734) | Sagamihara Kanagawa, Japan, 252-0375Yokohama City University Medical Center ( Site 0735) | Yokohama Kanagawa, Japan, 232-0024Nara Medical University Hospital ( Site 0744) | Kashihara Nara, Japan, 634-8522Kindai University Hospital ( Site 0743) | Sayama Osaka, Japan, 589-8511The University of Osaka Hospital ( Site 0742) | Suita Osaka, Japan, 565-0871Saitama Medical University International Medical Center ( Site 0737) | Hidaka Saitama, Japan, 350-1298Dokkyo Medical University Saitama Medical Center ( Site 0736) | Koshigaya Saitama, Japan, 343-8555Hamamatsu University Hospital ( Site 0748) | Hamamatsu Shizuoka, Japan, 431-3192Yamaguchi University Hospital ( Site 0746) | Ube Yamaguchi, Japan, 755-8505Chiba Cancer Center ( Site 0733) | Chiba , Japan, 260-8717Harasanshin Hospital ( Site 0747) | Fukuoka , Japan, 812-0033Nagano Municipal Hospital ( Site 0731) | Nagano , Japan, 381-8551Osaka Metropolitan University Hospital ( Site 0741) | Osaka , Japan, 545-8586Toranomon Hospital ( Site 0740) | Tokyo , Japan, 105-8470Nippon Medical School Hospital ( Site 0738) | Tokyo , Japan, 113-8603Tokyo Women's Medical University ( Site 0739) | Tokyo , Japan, 162-8666Hospital San Lucas Cardiologica del Sureste ( Site 2606) | Tuxtla Gutiérrez Chiapas, Mexico, 29090Hospital Civil de Guadalajara Fray Antonio Alcalde ( Site 2607) | Guadalajara Jalisco, Mexico, 44280Centro Estatal de Cancerologia de Chihuahua ( Site 2608) | Chihuahua City , Mexico, 31000Grupo Medico Camino SC ( Site 2613) | Mexico City , Mexico, 03310Centro Oncologico Internacional. SEDNA ( Site 2609) | Mexico City , Mexico, 04700Boca Raton Clinical Research QTO ( Site 2611) | Querétaro , Mexico, 76070Radboud University Medical Center ( Site 1606) | Nijmegen Gelderland, Netherlands, 6500 HBAntoni van Leeuwenhoek Ziekenhuis ( Site 1603) | Amsterdam North Holland, Netherlands, 1066 CXVrije Universiteit Medisch Centrum ( Site 1601) | Amsterdam North Holland, Netherlands, 1081 HVIsala Klinieken, Locatie Sophia ( Site 1604) | Zwolle Overijssel, Netherlands, 8025 ABFranciscus Gasthuis en Vlietland ( Site 1605) | Schiedam South Holland, Netherlands, 3118 JHMeander Medisch Centrum ( Site 1602) | Amersfoort Utrecht, Netherlands, 3813TZSt. Antonius Ziekenhuis ( Site 1600) | Utrecht , Netherlands, 3543 AZAuckland City Hospital ( Site 0321) | Auckland , New Zealand, 1023Hospital Nacional Carlos Alberto Seguin Escobedo ESSALUD ( Site 2700) | Arequipa Ariqipa, Peru, 04001Clinica Peruano Americana S.A. ( Site 2702) | Trujillo La Libertad, Peru, 13011Hospital Nacional Guillermo Almenara Irigoyen ( Site 2708) | Lima , Peru, 15033IPOR Instituto Peruano de Oncología & Radioterapia-Centro de Investigación ( Site 2706) | Lima , Peru, 15036Hospital Militar Central [Lima, Peru] ( Site 2704) | Lima , Peru, 15076Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 1710) | Poznan Greater Poland Voivodeship, Poland, 61-848Szpital Uniwersytecki nr 1 im. Dr. Antoniego Jurasza w Bydgoszczy ( Site 1720) | Bydgoszcz Kuyavian-Pomeranian Voivodeship, Poland, 85-094Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1716) | Bydgoszcz Kuyavian-Pomeranian Voivodeship, Poland, 85-796MICS Centrum Medyczne Torun ( Site 1718) | Torun Kuyavian-Pomeranian Voivodeship, Poland, 87-100Szpital Uniwersytecki w Krakowie ( Site 1707) | Krakow Lesser Poland Voivodeship, Poland, 30-688Radomskie Centrum Onkologii ( Site 1701) | Radom Masovian Voivodeship, Poland, 26-600Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1700) | Przemyśl Podkarpackie Voivodeship, Poland, 37-700Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1717) | Bytom Silesian Voivodeship, Poland, 41-900Szpital Wojewodzki im. Mikolaja Kopernika ( Site 1709) | Koszalin West Pomeranian Voivodeship, Poland, 75-581Twoja Przychodnia - Szczeciskie Centrum Medyczne ( Site 1721) | Szczecin West Pomeranian Voivodeship, Poland, 71-434Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 1810) | Krasnoyarsk Krasnoyarsk Krai, Russia, 660133SBIH City clinical hospital named after D.D. Pletniov ( Site 1813) | Moscow Moscow, Russia, 105077Russian Scientific Center of Roentgenoradiology ( Site 1800) | Moscow Moscow, Russia, 117997Volga District Medical Center Federal Medical and Biological Agency ( Site 1805) | Nizhny Novgorod Nizhny Novgorod Oblast, Russia, 603074Omsk Clinical Oncology Dispensary ( Site 1809) | Omsk Omsk Oblast, Russia, 644013Chonnam National University Hwasun Hospital ( Site 0406) | Jeollanam-do Jeonranamdo, South Korea, 58128National Cancer Center ( Site 0400) | Gyeonggi-do Kyonggi-do, South Korea, 10408Seoul National University Bundang Hospital ( Site 0401) | Seongnam-si Kyonggi-do, South Korea, 13620Kyungpook National University Chilgok Hospital ( Site 0404) | Daegu Kyongsangbuk-do, South Korea, 41404Seoul National University Hospital ( Site 0405) | Seoul , South Korea, 03080Severance Hospital Yonsei University Health System ( Site 0402) | Seoul , South Korea, 03722Asan Medical Center ( Site 0403) | Seoul , South Korea, 05505Instituto Catalan de Oncologia - ICO ( Site 1901) | L'Hospitalet de Llobregat Barcelona, Spain, 08908Institut Català d'Oncologia (ICO) - Girona ( Site 1900) | Girona Gerona, Spain, 17007Hospital Universitario Lucus Augusti ( Site 1905) | Lugo , Spain, 27003Hospital Universitario Ramon y Cajal ( Site 1902) | Madrid , Spain, 28034Hospital Clinico San Carlos ( Site 1906) | Madrid , Spain, 28040Hospital 12 de Octubre de Madrid ( Site 1903) | Madrid , Spain, 28041Hospital Virgen de la Macarena ( Site 1904) | Seville , Spain, 41009Kantonsspital St. Gallen ( Site 2000) | Sankt Gallen Canton of St. Gallen, Switzerland, 9007CHUV (centre hospitalier universitaire vaudois) ( Site 2002) | Lausanne Canton of Vaud, Switzerland, 1011Universitaetsspital Zuerich ( Site 2001) | Zurich Canton of Zurich, Switzerland, 8091Kantonsspital Graubuenden ( Site 2003) | Chur Kanton Graubünden, Switzerland, 7000Kaohsiung Chang Gung Memorial Hospital ( Site 0504) | Kaohsiung City , Taiwan, 83301National Cheng Kung University Hospital ( Site 0503) | Tainan , Taiwan, 70457National Taiwan University Hospital ( Site 0500) | Taipei , Taiwan, 100Taipei Veterans General Hospital ( Site 0501) | Taipei , Taiwan, 11217Chang Gung Medical Foundation. Linkou ( Site 0502) | Taoyuan , Taiwan, 33305Chulalongkorn Hospital, Medical Oncology Unit ( Site 0600) | Bangkok Bangkok, Thailand, 10330Ramathibodi Hospital. ( Site 0601) | Bangkok Bangkok, Thailand, 10400Faculty of Medicine Siriraj Hospital ( Site 0602) | Bangkok Bangkok, Thailand, 10700Srinagarind Hospital ( Site 0604) | Khon Kaen , Thailand, 40002Ankara Bilkent Sehir Hastanesi ( Site 2103) | Ankara Adana, Turkey (Türkiye), 06800Acibadem Adana Hastanesi ( Site 2106) | Adana , Turkey (Türkiye), 01130Ankara Universitesi Tip Fakultesi. ( Site 2101) | Ankara , Turkey (Türkiye), 06100Hacettepe Universitesi Tıp Fakultesi ( Site 2105) | Ankara , Turkey (Türkiye), 06230Istanbul Uni. Cerrahpasa Tip Fakultesi ( Site 2100) | Istanbul , Turkey (Türkiye), 34098Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 2102) | Izmir , Turkey (Türkiye), 35100Konya Necmettin Erbakan University Medical Faculty ( Site 2104) | Konya , Turkey (Türkiye), 42080Aberdeen Royal Infirmary ( Site 1315) | Aberdeen Aberdeen City, United Kingdom, AB25 2ZNRoyal Cornwall Hospitals NHS Trust ( Site 1317) | Truro Cornwall, United Kingdom, TR1 3LJUniversity College London Hospitals NHS Foundation Trust ( Site 1320) | London London, City of, United Kingdom, NW1 2BUROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1318) | London London, City of, United Kingdom, SW3 6JJVelindre Cancer Centre Hospital ( Site 1322) | Cardiff Wales, United Kingdom, CF14 2TL
Investigators
Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full Text)
Documents provided by Merck Sharp & Dohme LLC: Study Protocol and Statistical Analysis Plan  May 14, 2023