Study of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Who Are Receiving Chemotherapy and Radiation Therapy (MK-3475-975/KEYNOTE-975)

Esophageal Squamous Cell Carcinoma (ESCC) Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants With Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04210115
• Other study ID #: 3475-975
• Secondary ID: MK-3475-975KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 28, 2020
• Est. completion date: February 1, 2027

Study information

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

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of treatment with definitive chemoradiotherapy (dCRT) + pembrolizumab (MK-3475) compared to treatment with dCRT + placebo with respect to Event-free Survival (EFS) and Overall Survival (OS) in:

• participants whose tumors express Programmed Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10

• participants whose tumors express PD-L1 CPS ≥1

• all participants

The primary study hypotheses are that dCRT+ pembrolizumab is better than dCRT + placebo with respect to:

• EFS in participants whose tumors express PD-L1 CPS ≥10

• EFS in participants whose tumors express PD-L1 CPS ≥1

• EFS in all participants

• OS in participants whose tumors express PD-L1 CPS ≥10

• OS in participants whose tumors express PD-L1 CPS ≥1

• OS in all participants

Description:

Participants receive pembrolizumab or placebo PLUS one of two chemotherapy regimens PLUS radiation therapy for up to approximately one year. The chemotherapy regimens are either:

• FP (5-fluorouracil [5-FU] + cisplatin) or

• FOLFOX (5-FU + oxaliplatin + leucovorin or levoleucovorin).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 700
• Est. completion date: February 1, 2027
• Est. primary completion date: February 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically or cytologically confirmed diagnosis of CTX N+ M0 or cT2-T4a NX M0 ESCC, GEJC, EAC, or histologically or cytologically confirmed diagnosis of cTX N+ M1 cervical or upper thoracic esophageal carcinoma with supraclavicular lymph node metastases only

• Is deemed suitable for dCRT

• Is ineligible for curative surgery based on the documented opinion of a qualified medical/surgical/radiation oncologist.

• Is not expected to require tumor resection during the course of the study

• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days of the first dose of study treatment.

• Has adequate organ function.

• Male participants must use adequate contraception (a male condom plus partner use of an additional contraceptive method) unless confirmed to be azoospermic (vasectomized or secondary to medical cause) and refrain from donating sperm during the study treatment period and through 90 days after the last dose of chemotherapy.

• Female participants who are a Woman of Childbearing Potential (WOCBP) must use contraception that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, during the study treatment period through 180 days after the last dose of chemotherapy or 120 days after the last dose of pembrolizumab, whichever is greater, and agree not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period

• Female participants must not be pregnant or breastfeeding

Exclusion Criteria:

• Has direct invasion of tumor into adjacent organs such as the aorta or trachea or has radiographic evidence of >90 degree encasement or invasion of a major blood vessel, or of intratumoral cavitation.

• Has had major surgery other than for insertion of a feeding tube, open biopsy, or significant traumatic injury within 28 days prior to randomization, or anticipates the need for major surgery during study treatment; participants with gastric or esophageal fistulae are excluded

• Has had weight loss of >20% in the previous 3 months

• Has had prior chemotherapy or radiotherapy for esophageal cancer

• Has had a myocardial infarction within the past 6 months

• Has symptomatic congestive heart failure

• 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 (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137)

• Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention; administration of killed vaccines is allowed

• Has received any prior systemic anticancer therapy for esophageal cancer including investigational agents

• Has not recovered from all adverse events (AEs) due to previous non-anticancer therapies to =Grade 1 or Baseline

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded from the study. Participants with localized prostate cancer that has undergone potentially curative treatment can be enrolled in the study.

• Has severe hypersensitivity (=Grade 3) to pembrolizumab, any of the study chemotherapy agents, or their excipients

• Has an active autoimmune disease that has required systemic treatment in past 2 years

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis

• Has an active infection requiring systemic therapy

• Has a known history of human immunodeficiency virus (HIV) infection

• Has a known history of Hepatitis B or known active Hepatitis C virus infection

• Has a known history of active tuberculosis (TB; Bacillus tuberculosis)

• 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 (180 days for participants receiving cisplatin who are breastfeeding)

• Has had an allogenic tissue/solid organ transplant

Related Conditions & MeSH terms

• Carcinoma
• Esophageal Adenocarcinoma (EAC)
• Esophageal Neoplasms
• Esophageal Squamous Cell Carcinoma
• Esophageal Squamous Cell Carcinoma (ESCC)
• Gastroesophageal Junction Carcinoma (GEJC)

Intervention

Biological:
• pembrolizumab
IV infusion

Drug:
• placebo
IV infusion
• cisplatin
IV infusion
• 5-FU
IV infusion

Radiation:
• radiotherapy
external radiation

Drug:
• leucovorin
IV infusion
• levoleucovorin
IV infusion
• oxaliplatin
IV infusion

Locations

Country	Name	City	State
Argentina	CEMIC ( Site 0064)	Buenos Aires
Argentina	Hospital Municipal de Gastroenterologia Dr. Bonorino Udaondo ( Site 0066)	Buenos Aires
Argentina	Instituto Medico Alexander Fleming ( Site 0063)	Buenos Aires	Caba
Argentina	Fundacion Favaloro ( Site 0061)	Ciudad de Buenos Aires	Caba
Belgium	UCL Saint Luc ( Site 0162)	Brussels	Bruxelles-Capitale, Region De
Belgium	UZ Gent ( Site 0163)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 0161)	Leuven	Vlaams-Brabant
Belgium	AZ Delta ( Site 0165)	Roeselare	West-Vlaanderen
Brazil	Clinica de Oncologia Reichow ( Site 0085)	Blumenau	Santa Catarina
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0088)	Ijui	Rio Grande Do Sul
Brazil	Hospital Nossa Senhora da Conceicao ( Site 0087)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0081)	Sao Paulo
Canada	Cross Cancer Institute ( Site 0010)	Edmonton	Alberta
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0005)	Montreal	Quebec
Canada	The Ottawa Hospital - Cancer Care ( Site 0008)	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre ( Site 0011)	Toronto	Ontario
Canada	Sunnybrook Research Institute ( Site 0012)	Toronto	Ontario
Canada	CancerCare Manitoba ( Site 0002)	Winnipeg	Manitoba
Chile	Hospital Regional de Concepcion ( Site 0105)	Concepcion	Biobio
Chile	Centro de Cancer Nuestra Senora de la Esperanza ( Site 0104)	Santiago	Region M. De Santiago
Chile	Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0103)	Temuco	Araucania
Chile	Centro Investigación del Cáncer James Lind ( Site 0106)	Temuco	Araucania
China	Hunan Cancer Hospital ( Site 0515)	Changsha	Hunan
China	Sichuan Cancer Hospital ( Site 0527)	Chengdu	Sichuan
China	The 900th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army ( Si	Fuzhou	Fujian
China	Hangzhou First People's Hospital ( Site 0530)	Hangzhou	Zhejiang
China	Sir Run Run Shaw Hospital ( Site 0523)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0529)	Hangzhou	Zhejiang
China	Anhui Provincial Hospital-Oncology Radiotherapy Department ( Site 0531)	Hefei	Anhui
China	Huai an First People s Hospital ( Site 0526)	Huai An	Jiangsu
China	Jiangxi Cancer Hospital ( Site 0512)	Nanchang	Jiangxi
China	Jiangsu Cancer Hospital ( Site 0519)	Nanjing	Jiangsu
China	Shanghai Chest Hospital ( Site 0503)	Shangai	Shanghai
China	Shanghai Chest Hospital ( Site 0501)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0502)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital ( Site 0505)	Tianjin	Tianjin
China	Hubei Cancer Hospital ( Site 0514)	Wuhan	Hubei
China	The First Affiliated Hospital of Xiamen University ( Site 0538)	Xiamen	Fujian
China	The Affiliated Hospital of Xuzhou Medical University ( Site 0522)	Xuzhou	Jiangsu
China	Affiliated Hospital of Jiangsu University ( Site 0524)	Zhenjiang	Jiangsu
Czechia	Masarykuv onkologicky ustav-Klinika komplexni onkologicke pece ( Site 0721)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Olomouc-Onkologicka klinika ( Site 0720)	Olomouc	Olomoucky Kraj
Czechia	Fakultni nemocnice Ostrava-Klinika onkologicka ( Site 0719)	Ostrava	Moravskoslezsky Kraj
Czechia	Fakultni nemocnice v Motole-Onkologicka klinika 2. LF UK a FN Motol ( Site 0718)	Praha	Praha 5
Denmark	Rigshospitalet ( Site 0199)	Copenhagen	Hovedstaden
Denmark	Odense Universitetshospital ( Site 0200)	Odense	Syddanmark
Estonia	SA Pohja-Eesti Regionaalhaigla ( Site 0201)	Tallinn	Harjumaa
Estonia	SA Tartu Ulikooli Kliinikum ( Site 0202)	Tartu	Tartumaa
France	CHU Amiens Picardie Site Sud Amiens ( Site 0235)	Amiens	Somme
France	Institut Sainte Catherine ( Site 0228)	Avignon	Provence-Alpes-Cote-d Azur
France	Centre Francois Baclesse ( Site 0236)	Caen	Calvados
France	Centre Georges Francois Leclerc ( Site 0223)	Dijon	Cote-d Or
France	CHD Vendee ( Site 0227)	La Roche sur Yon	Vendee
France	CHU Limoges Hopital Dupuytren ( Site 0225)	Limoges	Haute-Vienne
France	CHU Hotel Dieu Nantes ( Site 0230)	Nantes	Pays-de-la-Loire
France	Institut Jean Godinot ( Site 0238)	Reims	Marne
France	Institut Curie - Centre Rene Huguenin ( Site 0237)	Saint-Cloud	Hauts-de-Seine
France	Institut De Cancerologie De Lorraine ( Site 0222)	Vandoeuvre les Nancy	Ain
Germany	Charite Campus Virchow Klinikum ( Site 0250)	Berlin
Germany	Facharztzentrum Eppendorf ( Site 0242)	Hamburg
Germany	Universitaetsklinikum Koeln ( Site 0251)	Koeln	Nordrhein-Westfalen
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz ( Site 0247)	Mainz	Rheinland-Pfalz
Germany	Universitaetsklinikum Muenster ( Site 0248)	Muenster	Nordrhein-Westfalen
Germany	Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0253)	Stuttgart	Baden-Wurttemberg
Guatemala	Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0122)	Guatemala
Guatemala	Gastrosoluciones ( Site 0126)	Guatemala
Guatemala	Grupo Medico Angeles ( Site 0121)	Guatemala
Guatemala	Medi-K Cayala ( Site 0124)	Guatemala
Guatemala	Oncomedica ( Site 0125)	Guatemala
Guatemala	Centro Medico Integral De Cancerología (CEMIC) ( Site 0123)	Quetzaltenango
Hong Kong	Pamela Youde Nethersole Eastern Hospital ( Site 0543)	Hong Kong
Hong Kong	Princess Margaret Hospital. ( Site 0542)	Hong Kong
Hong Kong	Queen Mary Hospital ( Site 0541)	Pokfulam
Hungary	Orszagos Onkologiai Intezet ( Site 0263)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0261)	Debrecen
Hungary	Bekes Megyei Kozponti Korhaz - Pandy Kalman Tagkorhaza ( Site 0262)	Gyula	Bekes
Hungary	Pecsi Tudomanyegyetem AOK ( Site 0265)	Pecs	Baranya
Italy	ASST Papa Giovanni XXIII ( Site 0296)	Bergamo
Italy	Azienda Socio Sanitaria Territoriale di Cremona ( Site 0299)	Cremona
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0292)	Milano
Italy	Istituto Nazionale Tumori IRCCS Fondazione Pascale-SC Oncologia Clinica Sperimentale Addome ( Site 0	Napoli
Italy	IRCCS Istituto Oncologico Veneto ( Site 0298)	Padova
Italy	Fondazione IRCCS Policlinico San Matteo-Oncology ( Site 0300)	Pavia	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana - Presidio Santa Chiara ( Site 0294)	Pisa	Toscana
Italy	Policlinico Universitario A. Gemelli ( Site 0297)	Roma
Italy	IRCCS Policlinico San Donato ( Site 0295)	San Donato Milanese	Milano
Japan	National Cancer Center Hospital East ( Site 0562)	Kashiwa	Chiba
Japan	Saitama Cancer Center ( Site 0564)	Kitaadachi-gun	Saitama
Japan	Aichi Cancer Center Hospital ( Site 0563)	Nagoya	Aichi
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 0566)	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital ( Site 0561)	Tokyo
Japan	Kanagawa Cancer Center ( Site 0565)	Yokohama	Kanagawa
Korea, Republic of	National Cancer Center ( Site 0626)	Goyang-si	Kyonggi-do
Korea, Republic of	Chonnam National University Hwasun Hospital ( Site 0625)	Hwasun Gun	Jeonranamdo
Korea, Republic of	Korea University Guro Hospital ( Site 0621)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 0622)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 0624)	Seoul
Korea, Republic of	Asan Medical Center ( Site 0623)	Songpagu	Seoul
Mexico	Cryptex Investigación Clínica S.A. de C.V. ( Site 0729)	Cuauhtémoc, Ciudad De México	Distrito Federal
Mexico	CENTRO HEMATO ONCOLOGICO PRIVADO-CHOP ( Site 0728)	Toluca de Lerdo
Peru	Clinica San Gabriel ( Site 0142)	Lima
Peru	Hospital Nacional Arzobispo Loayza ( Site 0143)	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas ( Site 0141)	Lima	Muni Metro De Lima
Peru	Detecta Clínica ( Site 0146)	Surquillo	Muni Metro De Lima
Philippines	Baguio General Hospital and Medical Center ( Site 0603)	Baguio City	Benguet
Philippines	Cebu Doctors University Hospital ( Site 0604)	Cebu City	Cebu
Philippines	The Medical City-Iloilo ( Site 0602)	Iloilo City	Iloilo
Philippines	St. Luke s Medical Center ( Site 0601)	Quezon	National Capital Region
Portugal	CHLN Hospital Santa Maria ( Site 0376)	Lisboa
Portugal	Hospital da Luz ( Site 0373)	Lisboa
Portugal	Inst. Portugues de Oncologia de Lisboa Francisco Gentil EPE ( Site 0372)	Lisboa
Portugal	Hospital Beatriz Angelo ( Site 0374)	Loures	Lisboa
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 0371)	Porto
Romania	MedEuropa Bucuresti - Centru de Radioterapie-Oncology ( Site 0400)	Bucure?ti	Bucuresti
Romania	S.C.Focus Lab Plus S.R.L ( Site 0395)	Bucuresti
Romania	Institutul Oncologic Prof.Dr. Ion Chiricuta Cluj-Napoca ( Site 0392)	Cluj-Napoca	Cluj
Romania	S.C. Radiotherapy Center Cluj S.R.L ( Site 0391)	Cluj-Napoca	Cluj
Romania	S.C. Centrul de Oncologie Sf. Nectarie SRL ( Site 0394)	Craiova	Dolj
Romania	Ovidius Clinical Hospital OCH-Oncology and Hematology ( Site 0393)	Ovidiu	Constanta
Romania	Centrul Medical Topmed ( Site 0398)	Targu-Mures	Mures
Russian Federation	Sverdlovsk Regional Oncology Hospital ( Site 0411)	Ekaterinburg	Sverdlovskaya Oblast
Russian Federation	Kaluga Regional Clinical Oncology Center ( Site 0424)	Kaluga	Kaluzskaja Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 0412)	Kazan	Tatarstan, Respublika
Russian Federation	FSAI Treatment and Rehabilitation Centre of the MoH and SD of RF ( Site 0429)	Moscow	Moskva
Russian Federation	Main Military Clinical Hospital n.a. N.N.Burdenko ( Site 0421)	Moscow	Moskva
Russian Federation	SBHI Samara Regional Clinical Oncology Dispensary ( Site 0420)	Samara	Samarskaya Oblast
Russian Federation	Medical institute named after Berezin Sergey ( Site 0417)	St. Petersburg	Sankt-Peterburg
Russian Federation	Pavlov First Saint Petersburg State Medical University ( Site 0426)	St. Petersburg	Sankt-Peterburg
Russian Federation	GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 0430)	Ufa	Baskortostan, Respublika
Taiwan	Chang Gung Med Foundation. Kaohsiung Branch ( Site 0643)	Kaohsiung
Taiwan	China Medical University Hospital ( Site 0646)	Taichung
Taiwan	Taichung Veterans General Hospital-Radiation Oncology ( Site 0647)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 0645)	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center ( Site 0644)	Taipei
Taiwan	National Taiwan University Hospital ( Site 0641)	Taipei
Taiwan	Chang Gung Medical Foundation. Linkou ( Site 0642)	Taoyuan
Turkey	Memorial Ankara Hastanesi ( Site 0461)	Ankara
Turkey	Istanbul University Cerrahpasa Medical Faculty ( Site 0452)	Istambul	Istanbul
Turkey	Göztepe Prof. Dr. Süleyman Yalçin Sehir Hastanesi-oncology ( Site 0451)	Istanbul
Turkey	Ege Universitesi Tip Fakultesi ( Site 0457)	Izmir
Turkey	Izmir Katip Celebi Universitesi Ataturk Egitim ve Arastirma Hastanesi ( Site 0458)	Izmir
United Kingdom	Aberdeen Royal Infirmary ( Site 0474)	Aberdeen	Aberdeen City
United Kingdom	Cambridge University Hospitals NHS Trust ( Site 0477)	Cambridge	Cambridgeshire
United Kingdom	Hammersmith Hospital-Medical Oncology ( Site 0471)	London	London, City Of
United Kingdom	Royal Free Hospital ( Site 0702)	London	England
United Kingdom	ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0283)	London	London, City Of
United Kingdom	University College Hospital NHS Foundation Trust ( Site 0701)	London	Worcestershire
United Kingdom	The Christie NHS Foundation Trust ( Site 0282)	Manchester
United Kingdom	Mount Vernon Hospital ( Site 0478)	Northwood
United Kingdom	Nottingham University Hospitals NHS Trust ( Site 0476)	Nottingham	Nottinghamshire
United Kingdom	Royal Marsden Hospital (Sutton) ( Site 0281)	Sutton	Surrey
United States	Greater Baltimore Medical Center ( Site 0031)	Baltimore	Maryland
United States	Dana Farber Cancer Center ( Site 0034)	Boston	Massachusetts
United States	University of Missouri ( Site 0688)	Columbia	Missouri
United States	Columbus Regional Research Institute ( Site 0047)	Columbus	Georgia
United States	Henry Ford Hospital ( Site 0685)	Detroit	Michigan
United States	Thompson Cancer Survival Center ( Site 0696)	Knoxville	Tennessee
United States	MemorialCare Health System - Long Beach Medical Center-Oncology ( Site 0691)	Long Beach	California
United States	University of Wisconsin Hospital and Clinics ( Site 0033)	Madison	Wisconsin
United States	Rutgers Cancer Institute of New Jersey ( Site 0695)	New Brunswick	New Jersey
United States	University Medical Center ( Site 0035)	New Orleans	Louisiana
United States	Weill Cornell Medical College ( Site 0053)	New York	New York
United States	Stephenson Cancer Center ( Site 0044)	Oklahoma City	Oklahoma
United States	Allegheny Health Network ( Site 0042)	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University Center for Health & Healing 2- CHH2 ( Site 0060)	Portland	Oregon
United States	Renown Regional Medical Center ( Site 0706)	Reno	Nevada
United States	Utah Cancer Specialists ( Site 0697)	Salt Lake City	Utah
United States	Cancer Care Northwest - Spokane Valley ( Site 0036)	Spokane Valley	Washington
United States	University of Kansas Cancer Center ( Site 0023)	Westwood	Kansas
United States	Cancer Center of Kansas ( Site 0058)	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  Chile,  China,  Czechia,  Denmark,  Estonia,  France,  Germany,  Guatemala,  Hong Kong,  Hungary,  Italy,  Japan,  Korea, Republic of,  Mexico,  Peru,  Philippines,  Portugal,  Romania,  Russian Federation,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Event-free Survival (EFS)	EFS is defined as the time from randomization to an event defined as local, regional, or distant radiological recurrence as assessed by the investigator; clinical recurrence as assessed by the investigator with histopathologic confirmation (in the absence of radiological disease recurrence by investigator assessment); or death from any cause, whichever occurs first.	Up to ~60 months
Primary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Up to ~72 months
Secondary	Number of participants with an adverse event (AE)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~15 months
Secondary	Number of participants discontinuing study treatment due to an adverse event (AE)	An AE is any untoward medical occurrence in a participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment.	Up to ~12 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary