Study of Chemoradiotherapy With or Without Pembrolizumab (MK-3475) For The Treatment of Locally Advanced Cervical Cancer (MK-3475-A18/KEYNOTE-A18/ENGOT-cx11/GOG-3047)

Uterine Cervical Neoplasms Clinical Trial

Official title:

A Randomized, Phase 3, Double-Blind Study of Chemoradiotherapy With or Without Pembrolizumab for the Treatment of High-risk, Locally Advanced Cervical Cancer (KEYNOTE-A18/ENGOT-cx11/GOG-3047)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04221945
• Other study ID #: 3475-A18
• Secondary ID: MK-3475-A18KEYNO
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: May 12, 2020
• Est. completion date: January 17, 2025

Study information

• Verified date: February 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 evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival. Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 980
• Est. completion date: January 17, 2025
• Est. primary completion date: January 17, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has high-risk locally advanced cervical cancer (LACC): The International Federation of Gynecology and Obstetrics (FIGO) 2014 Stage IB2-IIB (with node-positive disease) or FIGO 2014 Stages III-IVA
• Has histologically-confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
• Has not previously received any definitive surgical, radiation, or systemic therapy for cervical cancer, including investigational agents, and is immunotherapy-naïve
• Female participants must not be pregnant or breastfeeding and agree to use highly effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• Female participants must abstain from breastfeeding during the study intervention period and for at least 120 days after the last dose of pembrolizumab or placebo and 180 days following the end of chemoradiotherapy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study treatment
• Has provided a tissue sample from a core incisional or excisional biopsy of a tumor lesion
• Has radiographically evaluable disease, either measurable or non-measurable per RECIST 1.1, as assessed by the local site investigator/radiology
• Has adequate organ function within 7 days prior to the start of study treatment.

Exclusion Criteria:

• Has excluded subtypes of LACC
• Has FIGO 2014 Stage IVB disease
• Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy
• Has bilateral hydronephrosis, unless at least one side has been stented or resolved by positioning of nephrostomy or considered mild and not clinically significant in the opinion of the investigator
• Has anatomy or tumor geometry or any other reason or contraindication that cannot be treated with intracavitary brachytherapy or a combination of intracavitary and interstitial brachytherapy
• Has received a live vaccine within 30 days prior to the first dose of study treatment
• Has received treatment with systemic immunostimulatory agents, colony stimulating factors, interferons, interleukins and vaccine combinations within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1
• Has received prior therapy with an anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization
• 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 randomization
• Has any contraindication to the use of cisplatin
• 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 to the first dose of study treatment
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
• Has severe hypersensitivity to pembrolizumab and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• 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 history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
• Has had an allogenic tissue/solid organ transplant
• Has evidence of metastatic disease per RECIST 1.1 including lymph nodes above the first lumbar vertebra (L1) cephalad body, in the inguinal region

Related Conditions & MeSH terms

• Uterine Cervical Neoplasms

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Placebo for pembrolizumab
IV infusion
• Cisplatin
IV infusion

Radiation:
• External Beam Radiotherapy (EBRT)
Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed
• Brachytherapy
Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed

Locations

Country	Name	City	State
Australia	Monash Health-Monash Medical Centre ( Site 0970)	Clayton	Victoria
Australia	Royal Brisbane and Women s Hospital ( Site 0972)	Herston	Queensland
Australia	Peter MacCallum Cancer Centre ( Site 0971)	Melbourne	Victoria
Australia	St John of God Subiaco Hospital ( Site 0969)	Subiaco	Western Australia
Australia	Westmead Hospital ( Site 0973)	Westmead	New South Wales
Austria	Medizinische Universitat Graz ( Site 0569)	Graz	Steiermark
Austria	Medizinische Universitat Innsbruck ( Site 0566)	Innsbruck	Tirol
Austria	Medizinische Universität Wien ( Site 0567)	Vienna	Wien
Belgium	OLV Ziekenhuis ( Site 0352)	Aalst	Oost-Vlaanderen
Belgium	UZA University Hospital Antwerp ( Site 0351)	Edegem	Antwerpen
Belgium	AZ St Lucas ( Site 0349)	Gent	Oost-Vlaanderen
Belgium	UZ Leuven ( Site 0354)	Leuven	Vlaams-Brabant
Belgium	C.I.U. Hopital Ambroise Pare ( Site 0353)	Mons	Hainaut
Belgium	GZA Sint Augustinus ( Site 0356)	Wilrijk	Antwerpen
Brazil	Hospital das Clinicas da UFMG ( Site 0172)	Belo Horizonte	Minas Gerais
Brazil	Liga Norte Riograndense Contra o Cancer ( Site 0170)	Natal	Rio Grande Do Norte
Brazil	Hospital de Clínicas de Ribeirão Preto ( Site 0171)	Ribeirão Preto	Sao Paulo
Brazil	Instituto Nacional Do Cancer II ( Site 0173)	Rio de Janeiro
Brazil	Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0166)	São Paulo	Sao Paulo
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0101)	Montreal	Quebec
Canada	McGill University Health Centre ( Site 0105)	Montreal	Quebec
Canada	Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0	Quebec City	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0102)	Toronto	Ontario
Chile	Iram Cancer Research ( Site 0198)	Santiago	Region M. De Santiago
Chile	Sociedad Oncovida S.A. ( Site 0196)	Santiago	Region M. De Santiago
Chile	Centro Investigación del Cáncer James Lind ( Site 0194)	Temuco	Araucania
Chile	Oncocentro ( Site 0195)	Vina del Mar	Valparaiso
China	Peking Union Medical College Hospital ( Site 1001)	Beijing	Beijing
China	Hunan Cancer Hospital ( Site 1015)	Changsha	Hunan
China	Xiangya Hospital Central-South University ( Site 1009)	Changsha	Hunan
China	Sichuan Cancer Hospital ( Site 1018)	Chengdu	Sichuan
China	Chongqing Cancer Hospital ( Site 1030)	Chongqing	Chongqing
China	The First Affiliated Hospital.Sun Yat-sen University ( Site 1005)	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital ( Site 1004)	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital ( Site 1021)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 1013)	Harbin	Heilongjiang
China	Anhui Provincial Cancer Hospital ( Site 1007)	Hefei	Anhui
China	Anhui Provincial Hospital ( Site 1029)	Hefei	Anhui
China	Affiliated Cancer Hospital of Guangxi Medical University ( Site 1036)	Nanning	Guangxi
China	Shanghai Cancer Hospital ( Site 1000)	Shanghai	Shanghai
China	Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 1039)	Shanghai	Shanghai
China	The First Affiliated Hospital of Xinjiang Medical University ( Site 1012)	Urumqi	Xinjiang
China	The First Affiliated Hospital of Xiamen University ( Site 1025)	Xiamen	Fujian
Colombia	Instituto Nacional de Cancerologia E.S.E ( Site 0228)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 0227)	Cali	Valle Del Cauca
Colombia	Fundacion Valle del Lili ( Site 0230)	Cali	Valle Del Cauca
Colombia	Fundacion Centro de Investigacion Clinica CIC ( Site 0231)	Medellin	Antioquia
Czechia	Fakultni Nemocnice Brno Bohunice ( Site 0912)	Brno	Brno-mesto
Czechia	Fakultni nemocnice Ostrava ( Site 0909)	Ostrava	Moravskoslezsky Kraj
Czechia	Fakultni nemocnice Kralovske Vinohrady ( Site 0913)	Praha 10
France	CHU Jean Minjoz ( Site 0411)	Besancon	Doubs
France	Centre Hospitalier Lyon Sud ( Site 0413)	Pierre Benite	Rhone
France	Institut Claudius Regaud ( Site 0417)	Toulouse	Haute-Garonne
Germany	Charite Universitaetsmedizin Berlin ( Site 0442)	Berlin
Germany	Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 0452)	Dresden	Sachsen
Germany	Universitaetsklinikum Freiburg ( Site 0454)	Freiburg	Baden-Wurttemberg
Germany	Universitaetsklinikum Hamburg-Eppendorf ( Site 0445)	Hamburg
Germany	Universitaetsklinik Leipzig ( Site 0456)	Leipzig	Sachsen
Germany	Universitätsmedizin Mannheim-Department of Obstetrics and Gynecology ( Site 0443)	Mannheim	Baden-Wurttemberg
Germany	Klinikum der Universitaet in Muenchen ( Site 0446)	Muenchen	Bayern
Germany	Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0453)	Muenchen	Bayern
Greece	Alexandra General Hospital ( Site 0477)	Athens	Attiki
Greece	Hospital Hygeia ( Site 0478)	Athens	Attiki
Greece	General Hospital of Patras. St Andrews ( Site 0473)	Patras	Achaia
Greece	Euromedica General Clinic of Thessaloniki ( Site 0474)	Thessaloniki
Guatemala	Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0321)	Guatemala
Guatemala	Grupo Angeles SA ( Site 0319)	Guatemala
Guatemala	Medi-K Cayala ( Site 0318)	Guatemala
Guatemala	Oncologika S.A. ( Site 0323)	Guatemala
Guatemala	Oncomedica ( Site 0320)	Guatemala
Guatemala	Centro Medico Integral De Cancerología (CEMIC) ( Site 0322)	Quetzaltenango
Hungary	Orszagos Onkologiai Intezet ( Site 0846)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 0845)	Debrecen
Ireland	Cork University Hospital ( Site 0504)	Cork
Ireland	St James Hospital ( Site 0505)	Dublin
Israel	Rambam Medical Center ( Site 0815)	Haifa
Israel	Hadassah Medical Center. Ein Kerem ( Site 0816)	Jerusalem
Israel	Chaim Sheba Medical Center ( Site 0814)	Ramat Gan
Israel	Sourasky Medical Center ( Site 0819)	Tel Aviv
Italy	A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0541)	Bologna
Italy	Istituto di Candiolo - IRCCS ( Site 0546)	Candiolo	Piemonte
Italy	Ospedale Vito Fazzi ( Site 0547)	Lecce
Italy	Istituto Europeo di Oncologia ( Site 0536)	Milan	Milano
Italy	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0542)	Milano
Italy	IRCCS Ospedale San Raffaele ( Site 0539)	Milano
Italy	Fondazione Giovanni Pascale Di Napoli ( Site 0544)	Napoli
Italy	Policlinico Universitario Gemelli ( Site 0538)	Roma
Italy	Istituto Nazionale Tumori Regina Elena ( Site 0540)	Rome	Roma
Italy	A.O.U. Citta della Salute e della Scienza di Torino ( Site 0535)	Torino
Japan	National Hospital Organization Kyushu Cancer Center ( Site 1167)	Fukuoka
Japan	Saitama Medical University International Medical Center ( Site 1168)	Hidaka	Saitama
Japan	Kagoshima City Hospital ( Site 1166)	Kagoshima
Japan	National Cancer Center Hospital East ( Site 1159)	Kashiwa	Chiba
Japan	Saitama Cancer Center ( Site 1169)	Kitaadachi-gun	Saitama
Japan	Kurume University Hospital ( Site 1164)	Kurume	Fukuoka
Japan	National Hospital Organization Shikoku Cancer Center ( Site 1162)	Matsuyama	Ehime
Japan	Kyorin University Hospital ( Site 1158)	Mitaka	Tokyo
Japan	Aichi Cancer Center Hospital ( Site 1155)	Nagoya	Aichi
Japan	University of the Ryukyus Hospital ( Site 1156)	Nakagami-gun	Okinawa
Japan	Osaka International Cancer Institute ( Site 1161)	Osaka
Japan	Hokkaido University Hospital ( Site 1163)	Sapporo	Hokkaido
Japan	Iwate Medical University Hospital ( Site 1165)	Shiwa-gun	Iwate
Japan	Japanese Foundation for Cancer Research-Gynecologic Oncology ( Site 1171)	Tokyo
Japan	Keio University Hospital ( Site 1170)	Tokyo
Japan	National Cancer Center Hospital ( Site 1172)	Tokyo
Japan	Ehime University Hospital ( Site 1157)	Toon	Ehime
Korea, Republic of	Keimyung University Dongsan Medical Center ( Site 1066)	Daegu	Taegu-Kwangyokshi
Korea, Republic of	National Cancer Center ( Site 1065)	Goyang-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 1064)	Seoul
Korea, Republic of	Severance Hospital ( Site 1063)	Seoul
Korea, Republic of	Asan Medical Center ( Site 1062)	Seoul.	Seoul
Norway	Helse Bergen HF Haukeland Universitetssjukehus ( Site 0601)	Bergen	Hordaland
Norway	Oslo Universitetssykehus Radiumhospitalet ( Site 0600)	Oslo
Peru	Centro Medico Monte Carmelo ( Site 0289)	Arequipa	Ariqipa
Peru	Hospital Nacional Daniel Alcides Carrion ( Site 0293)	Callao	Lima
Peru	Hospital Nacional Arzobispo Loayza ( Site 0292)	Lima
Peru	Hospital Nacional Guillermo Almenara Irigoyen ( Site 0291)	Lima
Peru	Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 0290)	Lima
Peru	Clinica San Gabriel ( Site 0296)	San Miguel	Lima
Peru	Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 0287)	Trujillo	La Libertad
Russian Federation	Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine ( Site 0741)	Chelyabinsk	Chelyabinskaya Oblast
Russian Federation	Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0729)	Krasnoyarsk	Krasnoyarskiy Kray
Russian Federation	MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 0722)	Moscow	Moskva
Russian Federation	GBUZ SPb CRPCstmc(o) ( Site 0746)	Saint Petersburg	Sankt-Peterburg
Russian Federation	National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0725)	St. Petersburg	Sankt-Peterburg
Russian Federation	Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0734)	Yaroslavl	Yaroslavskaya Oblast
Spain	Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0637)	Badalona	Barcelona
Spain	Hospital Universitari Vall d Hebron ( Site 0634)	Barcelona
Spain	Complejo Hospitalario de Jaen ( Site 0632)	Jaen
Spain	HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 0638)	Pozuelo de Alarcon	Madrid
Spain	Hosp Clin Univ de Santiago ( Site 0629)	Santiago de Compostela	La Coruna
Spain	Hospital Clinico Universitario Lozano Blesa ( Site 0630)	Zaragoza
Sweden	Karolinska Universitetssjukhuset ( Site 0784)	Stockholm	Stockholms Lan
Taiwan	Mackay Memorial Hospital ( Site 1094)	Taipei
Taiwan	National Taiwan University Hospital ( Site 1095)	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital ( Site 1097)	Taoyuan
Thailand	Maharaj Nakorn Chiang Mai Hospital ( Site 1133)	Chiang Mai
Thailand	Songklanagarind Hospital ( Site 1130)	Hatyai	Songkhla
Thailand	Srinagarind Hospital. Khon Kaen University ( Site 1132)	Mueang	Khon Kaen
Thailand	Ramathibodi Hospital, Mahidol University ( Site 1131)	Rajthevee	Krung Thep Maha Nakhon
Turkey	Acibadem Adana Hastanesi ( Site 0756)	Adana
Turkey	Baskent Universitesi Ankara Hastanesi ( Site 0754)	Ankara
Turkey	I.U. Cerrahpasa Medical Faculty ( Site 0755)	Istambul	Istanbul
Ukraine	Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0876)	Kharkiv	Kharkivska Oblast
Ukraine	Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0882)	Lviv	Lvivska Oblast
United Kingdom	Royal Devon and Exeter Foundation Trust Hospital ( Site 0699)	Exeter	England
United Kingdom	ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 0701)	London	London, City Of
United Kingdom	Royal Marsden Hospital (Sutton)-Gynaecology Unit ( Site 0696)	London	Surrey
United States	University of New Mexico Comprehensive Cancer Center-Clinical Research Office ( Site 0019)	Albuquerque	New Mexico
United States	Texas Oncology-Austin Central ( Site 8006)	Austin	Texas
United States	Our Lady of the Lake Regional Medical Center. ( Site 0031)	Baton Rouge	Louisiana
United States	Sanford Bismarck Medical Center ( Site 0046)	Bismarck	North Dakota
United States	University of North Carolina at Chapel Hill ( Site 0025)	Chapel Hill	North Carolina
United States	Hollings Cancer Center ( Site 0007)	Charleston	South Carolina
United States	UVA Health System ( Site 0005)	Charlottesville	Virginia
United States	The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C	Columbus	Ohio
United States	Women's Cancer Care ( Site 0039)	Covington	Louisiana
United States	University of Colorado Health Sciences Center and Hospital ( Site 0028)	Denver	Colorado
United States	Karmanos Cancer Institute ( Site 0018)	Detroit	Michigan
United States	Willamette Valley Cancer Institute and Research Center ( Site 8000)	Eugene	Oregon
United States	Parkview Research Center at Parkview Regional Medical Center ( Site 0026)	Fort Wayne	Indiana
United States	Texas Oncology-Fort Worth Cancer Center ( Site 8001)	Fort Worth	Texas
United States	University of Kentucky Markey Cancer Center ( Site 0015)	Lexington	Kentucky
United States	UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0027)	Los Angeles	California
United States	Minnesota Oncology Hematology, PA ( Site 8007)	Minneapolis	Minnesota
United States	Smilow Cancer Center at Yale-New Haven ( Site 0023)	New Haven	Connecticut
United States	Hoag Memorial Hospital Presbyterian ( Site 0038)	Newport Beach	California
United States	AdventHealth Orlando-AdventHealth Medical Group Gynecological Oncology ( Site 0009)	Orlando	Florida
United States	HonorHealth Research Institute - Biltmore ( Site 8009)	Phoenix	Arizona
United States	Allegheny Health Network West Penn Hospital-Gynecologic Oncology ( Site 0030)	Pittsburgh	Pennsylvania
United States	Legacy Good Samaritan Medical Center ( Site 0013)	Portland	Oregon
United States	Virginia Commonwealth University ( Site 0024)	Richmond	Virginia
United States	UC Davis Comprehensive Cancer Center ( Site 0017)	Sacramento	California
United States	Texas Oncology-San Antonio Medical Center ( Site 8002)	San Antonio	Texas
United States	Sanford Gynecology Oncology ( Site 0003)	Sioux Falls	South Dakota
United States	Texas Oncology-The Woodlands ( Site 8003)	The Woodlands	Texas

Sponsors (3)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Czechia,  France,  Germany,  Greece,  Guatemala,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Norway,  Peru,  Russian Federation,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  Ukraine,  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 the Investigator	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, or by histopathologic confirmation of suspected disease progression, 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. Unequivocal progression of non-target lesions is also considered PD.	Up to approximately 38 months
Primary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 46 months
Secondary	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. Unequivocal progression of non-target lesions is also considered PD.	Up to approximately 38 months
Secondary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) at Month 24 as Assessed by the Investigator	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, or by histopathologic confirmation of suspected disease progression, 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. Unequivocal progression of non-target lesions is also considered PD. PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at Month 24 using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 38 months.	Up to approximately 38 months
Secondary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) at Month 24 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. Unequivocal progression of non-target lesions is also considered PD. PFS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the PFS rate at Month 24 using the entire PFS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 38 months.	Up to approximately 38 months
Secondary	Overall Survival (OS) at Month 36	OS is the time from randomization to death due to any cause. OS data will be cumulated to a certain cut-off date and the analysis will be performed via Kaplan-Meier approach to estimate the OS rate at Month 36 using the entire OS data up to the cut-off date. The cut-off date is event-driven and estimated to be approximately 46 months.	Up to approximately 46 months
Secondary	Complete Response (CR) Rate Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) at Week 12 as Assessed by the Investigator	For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) per RECIST 1.1, CR rate is defined as the percentage of participants who experienced a CR. CR data will be cumulated to a certain cut-off date and the analysis will be performed to estimate the CR rate at Week 12 using the entire CR data up to the cut-off date. The cut-off date is estimated to be approximately 38 months.	Up to approximately 38 months
Secondary	Complete Response (CR) Rate Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) at Week 12 as Assessed by Blinded Independent Central Review (BICR)	For participants who demonstrated a confirmed Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) per RECIST 1.1, CR rate is defined as the percentage of participants who experienced a CR. CR data will be cumulated to a certain cut-off date and the analysis will be performed to estimate the CR rate at Week 12 using the entire CR data up to the cut-off date. The cut-off date is estimated to be approximately 38 months.	Up to approximately 38 months
Secondary	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator	ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target and non-target lesions and also includes reduction of all nodal lesions to <10mm) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions and includes no unequivocal progression in non-target lesions) per RECIST 1.1.	Up to approximately 46 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 and non-target lesions and also includes reduction of all nodal lesions to <10mm) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions and includes no unequivocal progression in non-target lesions) per RECIST 1.1.	Up to approximately 46 months
Secondary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by the Investigator	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, or by histopathologic confirmation of suspected disease progression, 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. Unequivocal progression of non-target lesions is also considered PD.	Up to approximately 38 months
Secondary	Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants 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. Unequivocal progression of non-target lesions is also considered PD.	Up to approximately 38 months
Secondary	Overall Survival (OS) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by the Investigator	OS is the time from randomization to death due to any cause.	Up to approximately 46 months
Secondary	Overall Survival (OS) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by Blinded Independent Central Review (BICR)	OS is the time from randomization to death due to any cause.	Up to approximately 46 months
Secondary	Progression-Free Survival (PFS) After Next-Line Treatment (PFS 2) Following Discontinuation of Study Treatment	PFS is defined as the time from randomization to the first documented progressive disease (PD) on next-line treatment or death due to any cause, whichever occurs first, as assessed by the investigator.	Up to approximately 46 months
Secondary	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status Score	The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. The change from baseline in EORTC QLQ-C30 score will be presented.	Baseline and up to approximately 46 months
Secondary	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=not at all to 4=very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score indicates a better quality of life. The change from baseline in physical function (EORTC QLQ-C30 Items 1-5) score will be presented.	Baseline and up to approximately 46 months
Secondary	Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Cervical Cancer (EORTC QLQ-CX24) Score	The EORTC QLQ-CX24 is a questionnaire that rates the symptoms common to women with cervical cancer and evaluates the impact of disease and/or treatments. The 24 items use a 4-point scale (1=not at all to 4=very much) and are classified into 3 multi-item scales, 11 items with symptom experience, 3 items with body image, and 4 items with sexual/ vaginal functioning. The other items of the questionnaire are lymphedema, peripheral neuropathy, menopausal symptom, sexual worry, sexual activity, and sexual enjoyment. The change from baseline in EORTC QLQ-CX24 score will be presented.	Baseline and up to approximately 46 months
Secondary	Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 46 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 46 months

External Links

•   Merck Clinical Trials Information