A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)

Carcinoma, Renal Cell Clinical Trial

Official title:

An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination With Lenvatinib (MK-7902) vs Cabozantinib in Participants With Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04586231
• Other study ID #: 6482-011
• Secondary ID: MK-6482-011jRCT2
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 25, 2021
• Est. completion date: December 23, 2024

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will compare the efficacy and safety of belzutifan + lenvatinib versus cabozantinib in participants with advanced renal cell carcinoma (RCC) with clear cell component after prior therapy.

The primary hypothesis is that belzutifan + lenvatinib is superior to cabozantinib in terms of progression-free survival or overall survival.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 708
• Est. completion date: December 23, 2024
• Est. primary completion date: December 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Unresectable, locally advanced or metastatic clear cell renal cell carcinoma (RCC).

• Disease progression on or after an anti-programmed cell death-1/ligand 1 (PD-1/L1) therapy as either first or second-line treatment for locally advanced/metastatic RCC or as adjuvant treatment or neoadjuvant/adjuvant with progression on or within 6 months of last dose.

• Measurable disease per RECIST 1.1 criteria as assessed by local study investigator.

• Karnofsky performance status (KPS) score of at least 70% assessed within 10 days before randomization.

• Received no more than 2 prior systemic regimens including: one anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with progression on or within 6 months from the last dose of that regimen OR one or 2 regimens for locoregional/advanced disease

• Received only 1 prior antiPD-1/L1 therapy for adjuvant, neoadjuvant/adjuvant or locally advanced/metastatic RCC.

• A male participant is eligible to participate if he is abstinent from heterosexual intercourse or agrees to use contraception during the intervention period and for at least 7 days after the last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm, whichever occurs last, and 23 days after the last dose of cabozantinib.

• A female participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the intervention period and for at least 30 days after the last dose of study intervention in the belzutifan+ lenvatinib arm, or 120 days after the last dose of study intervention in the cabozantinib arm.

• Adequately controlled blood pressure.

• Adequate organ function.

Exclusion Criteria:

• A pulse oximeter reading <92% at rest, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen.

• Known additional malignancy that is progressing or has required active treatment within the past 3 years except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy.

• Known central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Clinically significant cardiac disease within 6 months of first dose of study intervention.

• Prolongation of QTc interval to >480 ms.

• Symptomatic pleural effusion (e.g.,cough, dyspnea, pleuritic chest pain) that is not clinically stable.

• Pre-existing =Grade 3 gastrointestinal or nongastrointestinal fistula.

• Moderate to severe hepatic impairment.

• History of significant bleeding within 3 months before randomization.

• History of solid organ transplantation.

• Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.

• Unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).

• Known hypersensitivity or allergy to the active pharmaceutical ingredients or any component of the study intervention formulations.

• Received colony-stimulating factors [eg, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GMCSF) or recombinant erythropoietin (EPO)] within 28 days before randomization.

• Prior treatment with belzutifan or another hypoxia-inducible factor (HIF)-2a inhibitor.

• Prior treatment with lenvatinib.

• Prior treatment with cabozantinib.

• Currently participating in a study of an investigational agent or using an investigational device.

• Active infection requiring systemic therapy.

• History of human immunodeficiency virus (HIV) infection.

• History of hepatitis B or known active hepatitis C infection.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Renal Cell

Intervention

Drug:
• Belzutifan
Immediate-release 40 mg tablet
• Lenvatinib
Capsule available in 4 mg and 10 mg dosages
• Cabozantinib
Tablet available in 20 mg, 40 mg and 60 mg dosages

Locations

Country	Name	City	State
Argentina	Asociación de Beneficencia Hospital Sirio Libanés ( Site 0804)	Buenos Aires
Argentina	Centro de Urología (CDU) ( Site 0803)	Caba	Buenos Aires
Argentina	Hospital Británico de Buenos Aires-Oncology ( Site 0801)	Ciudad autónoma de Buenos Aires	Buenos Aires
Argentina	Instituto Alexander Fleming ( Site 0800)	Ciudad Autónoma de Buenos Aires	Buenos Aires
Argentina	Sanatorio Británico-Clinical Oncology Department ( Site 0802)	Rosario	Santa Fe
Argentina	Sanatorio Parque ( Site 0806)	Rosario	Santa Fe
Australia	Lyell McEwin Hospital ( Site 4004)	Elizabeth Vale	South Australia
Australia	Peninsula Health Frankston Hospital ( Site 4001)	Frankston	Victoria
Australia	Peter MacCallum Cancer Centre-Parkville Cancer Clinical Trials Unit (PCCTU) ( Site 4010)	Melbourne	Victoria
Australia	GenesisCare North Shore ( Site 4011)	St Leonards	New South Wales
Austria	Medizinische Universitätsklinik Graz ( Site 1051)	Graz	Steiermark
Austria	Ordensklinikum Linz GmbH Elisabethinen-Urologie ( Site 1001)	Linz	Oberosterreich
Austria	Klinik Ottakring-1.Medizinische Abteilung - Zentrum für Onkologie und Hämatologie ( Site 1031)	Vienna	Wien
Austria	Krankenhaus der Barmherzigen Brüder Wien ( Site 1041)	Wien
Austria	Medizinische Universität Wien ( Site 1021)	Wien
Belgium	Institut Jules Bordet ( Site 1103)	Anderlecht	Bruxelles-Capitale, Region De
Belgium	Cliniques Universitaires Saint Luc - Bruxelles ( Site 1105)	Brussels	Bruxelles-Capitale, Region De
Belgium	Grand Hopital de Charleroi ( Site 1104)	Charleroi	Hainaut
Belgium	UZ Gent ( Site 1100)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 1101)	Leuven	Vlaams-Brabant
Belgium	CHU de Liege ( Site 1102)	Liege
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 0313)	Natal	Rio Grande Do Norte
Brazil	Centro Gaucho Integrado de Oncologia ( Site 0304)	Porto Alegre	Rio Grande Do Sul
Brazil	BP - A Beneficencia Portuguesa de São Paulo-Medical Oncology ( Site 0311)	Sao Paulo
Brazil	Hospital Paulistano - Amil Clinical Research ( Site 0308)	Sao Paulo
Canada	Tom Baker Cancer Centre ( Site 0109)	Calgary	Alberta
Canada	Cross Cancer Institute ( Site 0111)	Edmonton	Alberta
Canada	CISSS de la Monteregie-Centre ( Site 0103)	Greenfield Park	Quebec
Canada	Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0114)	Hamilton	Ontario
Canada	Kingston Health Sciences Centre ( Site 0105)	Kingston	Ontario
Canada	The Moncton Hospital ( Site 0101)	Moncton	New Brunswick
Canada	The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 0116)	Ottawa	Ontario
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec
Canada	CIUSSS de l Estrie - CHUS - Centre Hosp. Univ. Sherbrooke ( Site 0102)	Sherbrooke	Quebec
Canada	Sunnybrook Health Sciences - Odette Cancer Centre ( Site 0113)	Toronto	Ontario
Canada	BC Cancer Vancouver-Clinical Trials Unit ( Site 0110)	Vancouver	British Columbia
Chile	Bradfordhill-Clinical Area ( Site 0400)	Santiago	Region M. De Santiago
Chile	James Lind Centro de Investigación del Cáncer ( Site 0402)	Temuco	Araucania
Colombia	Instituto Nacional de Cancerología-Clinical Oncology ( Site 0500)	Bogotá	Cundinamarca
Colombia	Fundación Colombiana de Cancerología Clínica Vida ( Site 0505)	Medellin	Antioquia
Colombia	Fundación Cardiovascular de Colombia ( Site 0501)	Piedecuesta	Santander
Colombia	Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 0508)	Valledupar	Cesar
Czechia	Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 2203)	Brno	Brno-mesto
Czechia	Nemocnice Ceské Budejovice-Onkologicke oddeleni ( Site 2204)	Ceské Budejovice	Jihocesky Kraj
Czechia	Fakultni nemocnice Hradec Kralove-Klinika onkologie a radioterapie ( Site 2201)	Hradec Kralove
Czechia	Fakultni Thomayerova nemocnice-Onkologicka klinika 1. LF UK ( Site 2200)	Prague	Praha 4
Czechia	Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 2205)	Praha	Praha 5
Finland	HYKS ( Site 1800)	Helsinki	Uusimaa
Finland	Tampereen yliopistollinen sairaala ( Site 1801)	Tampere	Pirkanmaa
Finland	TYKS ( Site 1802)	Turku	Varsinais-Suomi
France	Institut de Cancerologie de l Ouest Site Paul Papin ( Site 1200)	Angers	Maine-et-Loire
France	CHU de Bordeaux- Hopital Saint Andre ( Site 1209)	Bordeaux	Gironde
France	Clinique Francois Chenieux ( Site 1210)	Limoges	Haute-Vienne
France	Centre Antoine Lacassagne ( Site 1217)	Nice	Alpes-Maritimes
France	Hopital Tenon ( Site 1213)	Paris
France	Institut Jean Godinot ( Site 1216)	Reims	Ain
France	Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 1201)	Saint Herblain	Loire-Atlantique
France	Institut de cancérologie Strasbourg Europe (ICANS) ( Site 1218)	Strasbourg	Alsace
France	Institut Claudius Regaud ( Site 1215)	Toulouse	Haute-Garonne
Germany	Universitaetsklinikum Aachen AOER ( Site 1317)	Aachen	Nordrhein-Westfalen
Germany	Charite Universitaetsmedizin Berlin ( Site 1321)	Berlin
Germany	HELIOS Klinikum Berlin-Buch ( Site 1311)	Berlin
Germany	Helios Klinikum Erfurt GmbH ( Site 1315)	Erfurt	Thuringen
Germany	Universitaetsklinikum Frankfurt ( Site 1301)	Frankfurt am Main	Hessen
Germany	Klinik fuer Urologie ( Site 1303)	Freiburg	Baden-Wurttemberg
Germany	Krankenhaus Martha Maria Halle-Doelau ( Site 1314)	Halle	Sachsen-Anhalt
Germany	NCT-Department of Medical Oncology ( Site 1320)	Heidelberg	Baden-Wurttemberg
Germany	Universitaetsklinikum des Saarlandes ( Site 1305)	Homburg/ Saar	Saarland
Germany	Klinikum Nuernberg Nord ( Site 1300)	Nuremberg	Bayern
Greece	Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 3304)	Athens	Attiki
Greece	Athens Medical Center ( Site 3303)	Athens	Attiki
Greece	ATTIKON GENERAL UNIVERSITY HOSPITAL ( Site 3301)	Chaidari	Attiki
Greece	UNIVERSITY HOSPITAL OF PATRAS-DIVISION OF ONCOLOGY ( Site 3302)	Patras	Achaia
Greece	European Interbalkan Medical Center-Oncology Department ( Site 3300)	Thessaloniki
Ireland	Mater Private Hospital - Dublin ( Site 3202)	Dublin
Ireland	Tallaght University Hospital ( Site 3200)	Dublin
Ireland	Mater Misericordiae University Hospital ( Site 3201)	Dublin 7	Dublin
Italy	Medical Oncology Ospedale San Donato ( Site 1404)	Arezzo
Italy	Azienda Ospedaliera Policlinico di Bari ( Site 1402)	Bari
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori ( Site 1407)	Meldola	Forli-Cesena
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1400)	Milano
Italy	IRCCS Ospedale San Raffaele ( Site 1409)	Milano
Italy	Ospedale San Luigi Gonzaga ( Site 1405)	Orbassano	Torino
Italy	Istituti Clinici Scientifici Maugeri Spa ( Site 1403)	Pavia
Italy	Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1410)	Roma
Italy	Istituto Clinico Humanitas Research Hospital ( Site 1406)	Rozzano	Milano
Italy	Azienda Ospedaliera S. Maria di Terni ( Site 1401)	Terni
Italy	Ospedale Maggiore Borgo Trento ( Site 1408)	Verona
Japan	Tokyo Medical and Dental University Hospital ( Site 5009)	Bunkyo-ku	Tokyo
Japan	Kyushu University Hospital ( Site 5005)	Fukuoka
Japan	Hamamatsu University School of Medicine University Hospital ( Site 5004)	Hamamatsu	Shizuoka
Japan	Nara Medical University Hospital ( Site 5002)	Kashihara	Nara
Japan	National Cancer Center Hospital East ( Site 5000)	Kashiwa	Chiba
Japan	Kobe City Medical Center General Hospital ( Site 5017)	Kobe	Hyogo
Japan	Toranomon Hospital ( Site 5001)	Minato-ku	Tokyo
Japan	Niigata University Medical & Dental Hospital ( Site 5013)	Niigata
Japan	Osaka International Cancer Institute ( Site 5016)	Osaka
Japan	Kindai University Hospital- Osakasayama Campus-Urology ( Site 5010)	Osakasayama	Osaka
Japan	Toho University Sakura Medical Center ( Site 5014)	Sakura	Chiba
Japan	Sapporo Medical University Hospital ( Site 5008)	Sapporo	Hokkaido
Japan	Osaka University Hospital ( Site 5012)	Suita	Osaka
Japan	Keio university hospital ( Site 5011)	Tokyo
Japan	Nippon Medical School Hospital ( Site 5006)	Tokyo
Japan	Tokyo Women's Medical University Adachi Medical Center ( Site 5015)	Tokyo
Japan	Fujita Health University ( Site 5003)	Toyoake	Aichi
Japan	Yokohama City University Hospital ( Site 5007)	Yokohama	Kanagawa
Korea, Republic of	Chonnam National University Hwasun Hospital-Oncology ( Site 4203)	Hwasun	Jeonranamdo
Korea, Republic of	Asan Medical Center ( Site 4200)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 4201)	Seoul
Netherlands	Antoni van Leeuwenhoek Ziekenhuis ( Site 1901)	Amsterdam	Noord-Holland
Netherlands	Amphia Hospital Location Molengracht ( Site 1912)	Breda	Noord-Brabant
Netherlands	Haga Ziekenhuis locatie Leyweg-Oncology ( Site 1917)	Den Haag	Zuid-Holland
Netherlands	Medisch Centrum Leeuwarden ( Site 1905)	Leeuwarden	Fryslan
Netherlands	Erasmus MC ( Site 1913)	Rotterdam	Zuid-Holland
Netherlands	Franciscus Gasthuis & Vlietland, Locatie Vlietland ( Site 1909)	Schiedam	Zuid-Holland
Netherlands	Zuyderland Medical Centre-Trialbureau Interne Geneeskunde ( Site 1904)	Sittard-Geleen	Limburg
Netherlands	Universitair Medisch Centrum Utrecht ( Site 1910)	Utrecht
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 2402)	Bydgoszcz	Kujawsko-pomorskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - O-Klinika Onkologii Klinicznej ( Site 240	Krakow	Malopolskie
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 2401)	Poznan	Wielkopolskie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 2400)	Warszawa	Mazowieckie
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2500)	Cluj Napoca	Cluj
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 2501)	Cluj Napoca	Cluj
Romania	Centrul de Oncologie "Sfântul Nectarie" ( Site 2502)	Craiova	Dolj
Russian Federation	Ivanovo Regional Oncology Dispensary ( Site 2616)	Ivanovo	Ivanovskaya Oblast
Russian Federation	MEDSI Clinical Hospital on Pyatnitsky Highway-Departmentof Antitumor Drug therapy ( Site 2618)	Krasnogorsk	Moskovskaya Oblast
Russian Federation	FSBI United Hospital with Polyclinic ( Site 2613)	Moscow	Moskva
Russian Federation	Hadassah Medical-Oncology department ( Site 2609)	Moscow	Moskovskaya Oblast
Russian Federation	SHI of Moscow City Oncology Clinical Hospital - 62 ( Site 2614)	Moscow	Moskva
Russian Federation	Volgograd Regional Uronephrological Center ( Site 2615)	Volzhsky	Volgogradskaya Oblast
Russian Federation	Yaroslavl Regional Cancer Hospital-Oncology ( Site 2619)	Yaroslavl	Yaroslavskaya Oblast
Spain	Complejo Hospitalario Universitario A Coruna ( Site 1502)	A Coruna	La Coruna
Spain	Hospital Clinic i Provincial ( Site 1500)	Barcelona
Spain	Hospital Santa Creu i Sant Pau ( Site 1501)	Barcelona
Spain	Hospital Universitari Vall d'Hebron-Departamento de Oncologia- VHIO ( Site 1507)	Barcelona
Spain	Hospital Clinico San Carlos ( Site 1504)	Madrid
Spain	Hospital General Universitario Gregorio Maranon ( Site 1505)	Madrid
Spain	Hospital Universitario 12 de Octubre-Medical Oncology ( Site 1508)	Madrid	Madrid, Comunidad De
Spain	Hospital Virgen del Rocio ( Site 1503)	Sevilla
Switzerland	Istituto Oncologica della Svizzera Italiana (IOSI) ( Site 1604)	Bellinzona	Ticino
Switzerland	Kantonsspital Graubuenden ( Site 1600)	Chur	Grisons
Switzerland	Hopitaux Universitaires de Geneve HUG ( Site 1602)	Geneva	Geneve
Switzerland	Universitaetsspital Zuerich ( Site 1601)	Zuerich	Zurich
United Kingdom	Aberdeen Royal Infirmary-Department of Oncology ( Site 3105)	Aberdeen	Aberdeen City
United Kingdom	Royal United Hospital Bath England ( Site 3108)	Bath	Bath And North East Somerset
United Kingdom	Imperial Healthcare NHS Trust Charing Cross Hospital ( Site 3107)	London	London, City Of
United Kingdom	Mount Vernon Cancer Centre ( Site 3101)	Northwood	London, City Of
United Kingdom	Nottingham University Hospitals NHS Trust. City Hospital Campus ( Site 3106)	Nottingham	England
United Kingdom	Southend University Hospital ( Site 3112)	Southend	Essex
United Kingdom	Singleton Hospital ( Site 3111)	Swansea	Wales
United Kingdom	Musgrove Park Hospital ( Site 3103)	Taunton	Somerset
United States	Lehigh Valley Hospital- Cedar Crest-Oncology Clinical Trials ( Site 0056)	Allentown	Pennsylvania
United States	University Cancer & Blood Center, LLC ( Site 0057)	Athens	Georgia
United States	Emory University Hospital ( Site 0012)	Atlanta	Georgia
United States	Lahey Hospital & Medical Center ( Site 0090)	Burlington	Massachusetts
United States	University of Vermont Medical Center ( Site 0001)	Burlington	Vermont
United States	Ironwood Cancer & Research Centers ( Site 0077)	Chandler	Arizona
United States	Levine Cancer Institute ( Site 0004)	Charlotte	North Carolina
United States	Rush University Medical Center ( Site 0040)	Chicago	Illinois
United States	University of Texas, Southwestern Medical Center ( Site 0015)	Dallas	Texas
United States	Duke Cancer Institute ( Site 0096)	Durham	North Carolina
United States	Parkview Cancer Institute ( Site 0088)	Fort Wayne	Indiana
United States	Cancer & Hematology Centers of Western Michigan ( Site 0018)	Grand Rapids	Michigan
United States	University of Mississippi Medical Ctr ( Site 0037)	Jackson	Mississippi
United States	R.J. Zuckerberg Cancer Center-Medical Oncology ( Site 0013)	Lake Success	New York
United States	Cancer Partners of Nebraska ( Site 0086)	Lincoln	Nebraska
United States	Cedars Sinai Medical Center ( Site 0027)	Los Angeles	California
United States	UCLA Hematology/Oncology - Santa Monica ( Site 0048)	Los Angeles	California
United States	Norton Cancer Institute - St. Matthews ( Site 0065)	Louisville	Kentucky
United States	Rutgers Cancer Institute of New Jersey ( Site 0078)	New Brunswick	New Jersey
United States	Tulane University School of Medicine ( Site 0098)	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center ( Site 0055)	New York	New York
United States	St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0095)	Orange	California
United States	UC Irvine Health ( Site 0029)	Orange	California
United States	AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlando ( Site 0003)	Orlando	Florida
United States	Orlando Health, Inc. ( Site 0035)	Orlando	Florida
United States	Illinois Cancer Care, PC ( Site 0008)	Peoria	Illinois
United States	Blue Ridge Cancer Care - Roanoke ( Site 0043)	Roanoke	Virginia
United States	HealthPartners Cancer Research Center-HealthPartners Frauenshuh Cancer Center ( Site 0005)	Saint Louis Park	Minnesota
United States	Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 7001)	Salt Lake City	Utah
United States	Providence Saint John's Health Center ( Site 0083)	Santa Monica	California
United States	Seattle Cancer Care Alliance-Renal/Melanoma/MCC ( Site 0093)	Seattle	Washington
United States	Georgetown University Medical Center ( Site 0006)	Washington	District of Columbia
United States	Confluence Health | Wenatchee Valley Hospital & Clinics ( Site 0061)	Wenatchee	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =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 =5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review will be presented.	Up to approximately 34 months
Primary	Overall Survival (OS)	OS is defined as time from randomization to death due to any cause.	Up to approximately 44 months
Secondary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	ORR is defined as the percentage of participants who have a complete response (CR: Disappearance of all target lesions) or a partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience a CR or PR as assessed by blinded independent central review based on RECIST 1.1 will be presented.	Up to approximately 24 months
Secondary	Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)	For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed partial response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR as assessed by blinded independent central review will be presented.	Up to approximately 44 months
Secondary	Number of Participants Who Experienced One or More Adverse Events (AEs)	An adverse event (AE) is 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 44 months
Secondary	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	An adverse event (AE) is 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 unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.	Up to approximately 44 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary