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)

• ClinicalTrials.gov Identifier: NCT04221945
• Recruitment Status: Active, not recruiting
• First Posted: January 9, 2020
• Last Update Posted: March 4, 2024
• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: GOG Foundation; European Network of Gynaecological Oncological Trial Groups (ENGOT)
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Uterine Cervical Neoplasms	Biological: Pembrolizumab; Drug: Placebo for pembrolizumab; Drug: Cisplatin; Radiation: External Beam Radiotherapy (EBRT); Radiation: Brachytherapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 980 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: May 12, 2020
• Estimated Primary Completion Date: January 17, 2025
• Estimated Study Completion Date: January 17, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: chemoradiotherapy + pembrolizumab; Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).	Biological: Pembrolizumab; IV infusion; Other Names: KEYTRUDA®; MK-3475; Drug: Cisplatin; IV infusion; Other Names: Platinol®; Platinol®-AQ; Radiation: External Beam Radiotherapy (EBRT); Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed; Radiation: Brachytherapy; Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed
Experimental: chemoradiotherapy + placebo for pembrolizumab; Participants receive placebo for pembrolizumab IV on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).	Drug: Placebo for pembrolizumab; IV infusion; Drug: Cisplatin; IV infusion; Other Names: Platinol®; Platinol®-AQ; Radiation: External Beam Radiotherapy (EBRT); Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed; Radiation: Brachytherapy; Given as a total radiotherapy dose of 80 Gy for volume-directed and 75 Gy for point-directed

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 38 months ]
   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.
2. Overall Survival (OS) [ Time Frame: Up to approximately 46 months ]
   OS is the time from randomization to death due to any cause.

Secondary Outcome Measures :

1. 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) [ Time Frame: Up to approximately 38 months ]
   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.
2. 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 [ Time Frame: Up to approximately 38 months ]
   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.
3. 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) [ Time Frame: Up to approximately 38 months ]
   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.
4. Overall Survival (OS) at Month 36 [ Time Frame: Up to approximately 46 months ]
   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.
5. 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 [ Time Frame: Up to approximately 38 months ]
   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.
6. 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) [ Time Frame: Up to approximately 38 months ]
   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.
7. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator [ Time Frame: Up to approximately 46 months ]
   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.
8. 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) [ Time Frame: Up to approximately 46 months ]
   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.
9. 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 [ Time Frame: Up to approximately 38 months ]
   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.
10. 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) [ Time Frame: Up to approximately 38 months ]
    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.
11. Overall Survival (OS) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by the Investigator [ Time Frame: Up to approximately 46 months ]
    OS is the time from randomization to death due to any cause.
12. Overall Survival (OS) in Programmed Cell Death 1 Ligand 1 (PD-L1) Positive Participants as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 46 months ]
    OS is the time from randomization to death due to any cause.
13. Progression-Free Survival (PFS) After Next-Line Treatment (PFS 2) Following Discontinuation of Study Treatment [ Time Frame: Up to approximately 46 months ]
    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.
14. 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 [ Time Frame: Baseline and up to approximately 46 months ]
    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.
15. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Function Score [ Time Frame: Baseline and up to approximately 46 months ]
    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.
16. 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 [ Time Frame: Baseline and up to approximately 46 months ]
    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.
17. Number of Participants Who Experience One or More Adverse Events (AEs) [ Time Frame: Up to approximately 46 months ]
    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.
18. Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to approximately 46 months ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

HonorHealth Research Institute - Biltmore ( Site 8009)

Phoenix, Arizona, United States, 85016

United States, California

UCLA Hematology/Oncology - Westwood (Building 200 Suite 120) ( Site 0027)

Los Angeles, California, United States, 90095

Hoag Memorial Hospital Presbyterian ( Site 0038)

Newport Beach, California, United States, 92663

UC Davis Comprehensive Cancer Center ( Site 0017)

Sacramento, California, United States, 95817

United States, Colorado

University of Colorado Health Sciences Center and Hospital ( Site 0028)

Denver, Colorado, United States, 80262

United States, Connecticut

Smilow Cancer Center at Yale-New Haven ( Site 0023)

New Haven, Connecticut, United States, 06510

United States, Florida

AdventHealth Orlando-AdventHealth Medical Group Gynecological Oncology ( Site 0009)

Orlando, Florida, United States, 32804

United States, Indiana

Parkview Research Center at Parkview Regional Medical Center ( Site 0026)

Fort Wayne, Indiana, United States, 46845

United States, Kentucky

University of Kentucky Markey Cancer Center ( Site 0015)

Lexington, Kentucky, United States, 40536

United States, Louisiana

Our Lady of the Lake Regional Medical Center. ( Site 0031)

Baton Rouge, Louisiana, United States, 70817

Women's Cancer Care ( Site 0039)

Covington, Louisiana, United States, 70433

United States, Michigan

Karmanos Cancer Institute ( Site 0018)

Detroit, Michigan, United States, 48201

United States, Minnesota

Minnesota Oncology Hematology, PA ( Site 8007)

Minneapolis, Minnesota, United States, 55404

United States, New Mexico

University of New Mexico Comprehensive Cancer Center-Clinical Research Office ( Site 0019)

Albuquerque, New Mexico, United States, 87106

United States, North Carolina

University of North Carolina at Chapel Hill ( Site 0025)

Chapel Hill, North Carolina, United States, 27514

United States, North Dakota

Sanford Bismarck Medical Center ( Site 0046)

Bismarck, North Dakota, United States, 58501

United States, Ohio

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C

Columbus, Ohio, United States, 43210

United States, Oregon

Willamette Valley Cancer Institute and Research Center ( Site 8000)

Eugene, Oregon, United States, 97401

Legacy Good Samaritan Medical Center ( Site 0013)

Portland, Oregon, United States, 97210

United States, Pennsylvania

Allegheny Health Network West Penn Hospital-Gynecologic Oncology ( Site 0030)

Pittsburgh, Pennsylvania, United States, 15244

United States, South Carolina

Hollings Cancer Center ( Site 0007)

Charleston, South Carolina, United States, 29425

United States, South Dakota

Sanford Gynecology Oncology ( Site 0003)

Sioux Falls, South Dakota, United States, 57104

United States, Texas

Texas Oncology-Austin Central ( Site 8006)

Austin, Texas, United States, 78731

Texas Oncology-Fort Worth Cancer Center ( Site 8001)

Fort Worth, Texas, United States, 76104

Texas Oncology-San Antonio Medical Center ( Site 8002)

San Antonio, Texas, United States, 78240

Texas Oncology-The Woodlands ( Site 8003)

The Woodlands, Texas, United States, 77380

United States, Virginia

UVA Health System ( Site 0005)

Charlottesville, Virginia, United States, 22908

Virginia Commonwealth University ( Site 0024)

Richmond, Virginia, United States, 23219

Australia, New South Wales

Westmead Hospital ( Site 0973)

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Royal Brisbane and Women s Hospital ( Site 0972)

Herston, Queensland, Australia, 4029

Australia, Victoria

Monash Health-Monash Medical Centre ( Site 0970)

Clayton, Victoria, Australia, 3168

Peter MacCallum Cancer Centre ( Site 0971)

Melbourne, Victoria, Australia, 3000

Australia, Western Australia

St John of God Subiaco Hospital ( Site 0969)

Subiaco, Western Australia, Australia, 6008

Austria

Medizinische Universitat Graz ( Site 0569)

Graz, Steiermark, Austria, 8036

Medizinische Universitat Innsbruck ( Site 0566)

Innsbruck, Tirol, Austria, 6020

Medizinische Universität Wien ( Site 0567)

Vienna, Wien, Austria, 1090

Belgium

UZA University Hospital Antwerp ( Site 0351)

Edegem, Antwerpen, Belgium, 2650

GZA Sint Augustinus ( Site 0356)

Wilrijk, Antwerpen, Belgium, 2610

C.I.U. Hopital Ambroise Pare ( Site 0353)

Mons, Hainaut, Belgium, 7000

OLV Ziekenhuis ( Site 0352)

Aalst, Oost-Vlaanderen, Belgium, 9300

AZ St Lucas ( Site 0349)

Gent, Oost-Vlaanderen, Belgium, 9000

UZ Leuven ( Site 0354)

Leuven, Vlaams-Brabant, Belgium, 3000

Brazil

Hospital das Clinicas da UFMG ( Site 0172)

Belo Horizonte, Minas Gerais, Brazil, 30130-100

Liga Norte Riograndense Contra o Cancer ( Site 0170)

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

Hospital de Clínicas de Ribeirão Preto ( Site 0171)

Ribeirão Preto, Sao Paulo, Brazil, 14048900

Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0166)

São Paulo, Sao Paulo, Brazil, 04014-002

Instituto Nacional Do Cancer II ( Site 0173)

Rio de Janeiro, Brazil, 20220-410

Canada, Ontario

Princess Margaret Cancer Centre ( Site 0102)

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0101)

Montreal, Quebec, Canada, H2X 0A9

McGill University Health Centre ( Site 0105)

Montreal, Quebec, Canada, H4A 3J1

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 0

Quebec City, Quebec, Canada, G1J 1Z4

Chile

Centro Investigación del Cáncer James Lind ( Site 0194)

Temuco, Araucania, Chile, 4800827

Sociedad Oncovida S.A. ( Site 0196)

Santiago, Region M. De Santiago, Chile, 7510032

Iram Cancer Research ( Site 0198)

Santiago, Region M. De Santiago, Chile, 7630370

Oncocentro ( Site 0195)

Vina del Mar, Valparaiso, Chile

China, Anhui

Anhui Provincial Hospital ( Site 1029)

Hefei, Anhui, China, 230001

Anhui Provincial Cancer Hospital ( Site 1007)

Hefei, Anhui, China, 230031

China, Beijing

Peking Union Medical College Hospital ( Site 1001)

Beijing, Beijing, China, 100730

China, Chongqing

Chongqing Cancer Hospital ( Site 1030)

Chongqing, Chongqing, China, 400030

China, Fujian

The First Affiliated Hospital of Xiamen University ( Site 1025)

Xiamen, Fujian, China, 361003

China, Guangdong

The First Affiliated Hospital.Sun Yat-sen University ( Site 1005)

Guangzhou, Guangdong, China, 510080

China, Guangxi

Affiliated Cancer Hospital of Guangxi Medical University ( Site 1036)

Nanning, Guangxi, China, 530021

China, Heilongjiang

Harbin Medical University Cancer Hospital ( Site 1013)

Harbin, Heilongjiang, China, 150081

China, Hunan

Hunan Cancer Hospital ( Site 1015)

Changsha, Hunan, China, 233004

Xiangya Hospital Central-South University ( Site 1009)

Changsha, Hunan, China, 410008

China, Shanghai

Shanghai Cancer Hospital ( Site 1000)

Shanghai, Shanghai, China, 200032

Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 1039)

Shanghai, Shanghai, China, 201204

China, Sichuan

Sichuan Cancer Hospital ( Site 1018)

Chengdu, Sichuan, China, 610041

China, Xinjiang

The First Affiliated Hospital of Xinjiang Medical University ( Site 1012)

Urumqi, Xinjiang, China, 830054

China, Zhejiang

Zhejiang Provincial People's Hospital ( Site 1021)

Hangzhou, Zhejiang, China, 310014

Zhejiang Cancer Hospital ( Site 1004)

Hangzhou, Zhejiang, China, 310022

Colombia

Fundacion Centro de Investigacion Clinica CIC ( Site 0231)

Medellin, Antioquia, Colombia, 050021

Instituto Nacional de Cancerologia E.S.E ( Site 0228)

Bogota, Distrito Capital De Bogota, Colombia, 110321

Fundacion Valle del Lili ( Site 0230)

Cali, Valle Del Cauca, Colombia, 760032

Centro Medico Imbanaco de Cali S.A ( Site 0227)

Cali, Valle Del Cauca, Colombia, 760042

Czechia

Fakultni Nemocnice Brno Bohunice ( Site 0912)

Brno, Brno-mesto, Czechia, 602 00

Fakultni nemocnice Ostrava ( Site 0909)

Ostrava, Moravskoslezsky Kraj, Czechia, 708 52

Fakultni nemocnice Kralovske Vinohrady ( Site 0913)

Praha 10, Czechia, 100 34

France

CHU Jean Minjoz ( Site 0411)

Besancon, Doubs, France, 25000

Institut Claudius Regaud ( Site 0417)

Toulouse, Haute-Garonne, France, 31059

Centre Hospitalier Lyon Sud ( Site 0413)

Pierre Benite, Rhone, France, 69310

Germany

Universitaetsklinikum Freiburg ( Site 0454)

Freiburg, Baden-Wurttemberg, Germany, 79106

Universitätsmedizin Mannheim-Department of Obstetrics and Gynecology ( Site 0443)

Mannheim, Baden-Wurttemberg, Germany, 68167

Klinikum der Universitaet in Muenchen ( Site 0446)

Muenchen, Bayern, Germany, 80336

Klinikum Rechts der Isar. Technischen Universitaet Muenchen ( Site 0453)

Muenchen, Bayern, Germany, 81675

Universitaetsklinikum Carl Gustav Carus der Technischen Univ ( Site 0452)

Dresden, Sachsen, Germany, 01307

Universitaetsklinik Leipzig ( Site 0456)

Leipzig, Sachsen, Germany, 04103

Charite Universitaetsmedizin Berlin ( Site 0442)

Berlin, Germany, 13353

Universitaetsklinikum Hamburg-Eppendorf ( Site 0445)

Hamburg, Germany, 20246

Greece

General Hospital of Patras. St Andrews ( Site 0473)

Patras, Achaia, Greece, 262 00

Alexandra General Hospital ( Site 0477)

Athens, Attiki, Greece, 11528

Hospital Hygeia ( Site 0478)

Athens, Attiki, Greece, 151 23

Euromedica General Clinic of Thessaloniki ( Site 0474)

Thessaloniki, Greece, 546 45

Guatemala

Centro de Investigaciones Clinicas de Latinoamerica S.A. - CELAN ( Site 0321)

Guatemala, Guatemala, 01010

Oncologika S.A. ( Site 0323)

Guatemala, Guatemala, 01010

Oncomedica ( Site 0320)

Guatemala, Guatemala, 01010

Grupo Angeles SA ( Site 0319)

Guatemala, Guatemala, 01015

Medi-K Cayala ( Site 0318)

Guatemala, Guatemala, 01016

Centro Medico Integral De Cancerología (CEMIC) ( Site 0322)

Quetzaltenango, Guatemala, 09002

Hungary

Orszagos Onkologiai Intezet ( Site 0846)

Budapest, Hungary, 1122

Debreceni Egyetem Klinikai Kozpont ( Site 0845)

Debrecen, Hungary, 4032

Ireland

Cork University Hospital ( Site 0504)

Cork, Ireland, T12 DC4A

St James Hospital ( Site 0505)

Dublin, Ireland, D8

Israel

Rambam Medical Center ( Site 0815)

Haifa, Israel, 3109601

Hadassah Medical Center. Ein Kerem ( Site 0816)

Jerusalem, Israel, 9112001

Chaim Sheba Medical Center ( Site 0814)

Ramat Gan, Israel, 5262000

Sourasky Medical Center ( Site 0819)

Tel Aviv, Israel, 6423906

Italy

Istituto Europeo di Oncologia ( Site 0536)

Milan, Milano, Italy, 20141

Istituto di Candiolo - IRCCS ( Site 0546)

Candiolo, Piemonte, Italy, 10060

Istituto Nazionale Tumori Regina Elena ( Site 0540)

Rome, Roma, Italy, 00144

A.O. Universitaria Policlinico S. Orsola-Malpighi ( Site 0541)

Bologna, Italy, 40138

Ospedale Vito Fazzi ( Site 0547)

Lecce, Italy, 73100

IRCCS Ospedale San Raffaele ( Site 0539)

Milano, Italy, 20132

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 0542)

Milano, Italy, 20133

Fondazione Giovanni Pascale Di Napoli ( Site 0544)

Napoli, Italy, 80131

Policlinico Universitario Gemelli ( Site 0538)

Roma, Italy, 00168

A.O.U. Citta della Salute e della Scienza di Torino ( Site 0535)

Torino, Italy, 10126

Japan

Aichi Cancer Center Hospital ( Site 1155)

Nagoya, Aichi, Japan, 464-8681

National Cancer Center Hospital East ( Site 1159)

Kashiwa, Chiba, Japan, 2778577

National Hospital Organization Shikoku Cancer Center ( Site 1162)

Matsuyama, Ehime, Japan, 791-0280

Ehime University Hospital ( Site 1157)

Toon, Ehime, Japan, 790-0295

Kurume University Hospital ( Site 1164)

Kurume, Fukuoka, Japan, 830-0011

Hokkaido University Hospital ( Site 1163)

Sapporo, Hokkaido, Japan, 060-8648

Iwate Medical University Hospital ( Site 1165)

Shiwa-gun, Iwate, Japan, 028-3695

University of the Ryukyus Hospital ( Site 1156)

Nakagami-gun, Okinawa, Japan, 903-0215

Saitama Medical University International Medical Center ( Site 1168)

Hidaka, Saitama, Japan, 350-1298

Saitama Cancer Center ( Site 1169)

Kitaadachi-gun, Saitama, Japan, 362-0806

Kyorin University Hospital ( Site 1158)

Mitaka, Tokyo, Japan, 181-8611

National Hospital Organization Kyushu Cancer Center ( Site 1167)

Fukuoka, Japan, 811-1395

Kagoshima City Hospital ( Site 1166)

Kagoshima, Japan, 890-8760

Osaka International Cancer Institute ( Site 1161)

Osaka, Japan, 541-8567

National Cancer Center Hospital ( Site 1172)

Tokyo, Japan, 104-0045

Japanese Foundation for Cancer Research-Gynecologic Oncology ( Site 1171)

Tokyo, Japan, 135-8550

Keio University Hospital ( Site 1170)

Tokyo, Japan, 160-8582

Korea, Republic of

National Cancer Center ( Site 1065)

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

Asan Medical Center ( Site 1062)

Seoul., Seoul, Korea, Republic of, 05505

Keimyung University Dongsan Medical Center ( Site 1066)

Daegu, Taegu-Kwangyokshi, Korea, Republic of, 42601

Severance Hospital ( Site 1063)

Seoul, Korea, Republic of, 03722

Samsung Medical Center ( Site 1064)

Seoul, Korea, Republic of, 06351

Norway

Helse Bergen HF Haukeland Universitetssjukehus ( Site 0601)

Bergen, Hordaland, Norway, 5021

Oslo Universitetssykehus Radiumhospitalet ( Site 0600)

Oslo, Norway, 0379

Peru

Centro Medico Monte Carmelo ( Site 0289)

Arequipa, Ariqipa, Peru, 04001

Hospital de Alta Complejidad de La Libertad Virgen de La Puerta ( Site 0287)

Trujillo, La Libertad, Peru, 13013

Hospital Nacional Daniel Alcides Carrion ( Site 0293)

Callao, Lima, Peru, 07021

Clinica San Gabriel ( Site 0296)

San Miguel, Lima, Peru, 15087

Instituto de Oncologia y Radioterapia Clinica Ricardo Palma ( Site 0290)

Lima, Peru, 15036

Hospital Nacional Arzobispo Loayza ( Site 0292)

Lima, Peru, 15082

Hospital Nacional Guillermo Almenara Irigoyen ( Site 0291)

Lima, Peru, 15082

Russian Federation

Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine ( Site 0741)

Chelyabinsk, Chelyabinskaya Oblast, Russian Federation, 454087

Krasnoyarsk Regional Clinical Oncological Dispensary ( Site 0729)

Krasnoyarsk, Krasnoyarskiy Kray, Russian Federation, 660133

MSROI named after P.A. Hertsen branch of FSBI NMRC Radiology ( Site 0722)

Moscow, Moskva, Russian Federation, 125284

GBUZ SPb CRPCstmc(o) ( Site 0746)

Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758

National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 0725)

St. Petersburg, Sankt-Peterburg, Russian Federation, 197758

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 0734)

Yaroslavl, Yaroslavskaya Oblast, Russian Federation, 150054

Spain

Hospital Germans Trias i Pujol-Instituto Catalán de Oncología de Badalona ( Site 0637)

Badalona, Barcelona, Spain, 08916

Hosp Clin Univ de Santiago ( Site 0629)

Santiago de Compostela, La Coruna, Spain, 15706

HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 0638)

Pozuelo de Alarcon, Madrid, Spain, 28223

Hospital Universitari Vall d Hebron ( Site 0634)

Barcelona, Spain, 08035

Complejo Hospitalario de Jaen ( Site 0632)

Jaen, Spain, 23007

Hospital Clinico Universitario Lozano Blesa ( Site 0630)

Zaragoza, Spain, 50009

Sweden

Karolinska Universitetssjukhuset ( Site 0784)

Stockholm, Stockholms Lan, Sweden, 171 76

Taiwan

National Taiwan University Hospital ( Site 1095)

Taipei, Taiwan, 100

Mackay Memorial Hospital ( Site 1094)

Taipei, Taiwan, 104

Linkou Chang Gung Memorial Hospital ( Site 1097)

Taoyuan, Taiwan, 333

Thailand

Srinagarind Hospital. Khon Kaen University ( Site 1132)

Mueang, Khon Kaen, Thailand, 40002

Ramathibodi Hospital, Mahidol University ( Site 1131)

Rajthevee, Krung Thep Maha Nakhon, Thailand, 10400

Songklanagarind Hospital ( Site 1130)

Hatyai, Songkhla, Thailand, 90110

Maharaj Nakorn Chiang Mai Hospital ( Site 1133)

Chiang Mai, Thailand, 50200

Turkey

I.U. Cerrahpasa Medical Faculty ( Site 0755)

Istambul, Istanbul, Turkey, 34093

Acibadem Adana Hastanesi ( Site 0756)

Adana, Turkey, 01130

Baskent Universitesi Ankara Hastanesi ( Site 0754)

Ankara, Turkey, 06490

Ukraine

Grigoriev Institute for medical Radiology NAMS of Ukraine ( Site 0876)

Kharkiv, Kharkivska Oblast, Ukraine, 61024

Lviv State Oncology Regional Treatment and Diagnostic Center ( Site 0882)

Lviv, Lvivska Oblast, Ukraine, 79031

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, SW3 6JJ

Royal Marsden Hospital (Sutton)-Gynaecology Unit ( Site 0696)

London, Surrey, United Kingdom, SM3 5PT

Sponsors and Collaborators

Merck Sharp & Dohme LLC

GOG Foundation

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

More Information

Additional Information:

Merck Clinical Trials Information 

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT04221945
• Other Study ID Numbers: 3475-A18; MK-3475-A18 ( Other Identifier: Merck ); KEYNOTE-A18 ( Other Identifier: Merck ); ENGOT-cx11 ( Other Identifier: European Network for Gynaecological Oncological Trial groups ); 205189 ( Registry Identifier: JAPAC-CTI ); GOG-3047 ( Other Identifier: Gynecologic Oncology Group Foundation ); 2022-501972-25-00 ( Registry Identifier: EU CT ); 2019-003152-37 ( EudraCT Number )
• First Posted: January 9, 2020
• Last Update Posted: March 4, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

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

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme LLC:

Programmed Cell Death Receptor 1 (PD-1, PD1); Programmed Cell Death Receptor Ligand 1 (PD-L1, PDL1); Programmed Cell Death Receptor Ligand 2 (PD-L2, PDL2)

Additional relevant MeSH terms:

Uterine Cervical Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Cisplatin; Pembrolizumab; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action