Study of Pembrolizumab (MK-3475) in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Participants With Newly Diagnosed Endometrial Cancer After Surgery With Curative Intent (MK-3475-B21 / KEYNOTE-B21 / ENGOT-en11 / GOG-3053)

NCT04634877Active, Not RecruitingPHASE3INTERVENTIONAL

Summary

The purpose of this study is to compare pembrolizumab + adjuvant chemotherapy with placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to disease-free survival (DFS) as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to overall survival (OS). The primary hypotheses are that pembrolizumab + adjuvant chemotherapy is superior to placebo + adjuvant chemotherapy, with or without radiotherapy, with respect to DFS as assessed radiographically by the investigator or by histopathologic confirmation of suspected disease recurrence, and with respect to OS.

Key Facts

Lead Sponsor

Merck Sharp & Dohme LLC

Enrollment

990

Start Date

2021-01-10

Completion Date

2026-09-15

Study Type

INTERVENTIONAL

Official Title

A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Adjuvant Chemotherapy With or Without Radiotherapy for the Treatment of Newly Diagnosed High-Risk Endometrial Cancer After Surgery With Curative Intent (KEYNOTE-B21 / ENGOT-en11 / GOG-3053)

Interventions

PembrolizumabCarboplatinPaclitaxelPlacebo for pembrolizumabDocetaxelCisplatinExternal Beam Radiotherapy (EBRT)Cisplatin (as radiosensitizer)Brachytherapy

Conditions

Endometrial Neoplasms

Eligibility

Age Range

18 Years+

Sex

FEMALE

Inclusion Criteria:

* Has a histologically confirmed new diagnosis of Endometrial Carcinoma or Carcinosarcoma (Mixed Mullerian Tumor) and:

  * Has undergone curative intent surgery that included hysterectomy and bilateral salpingo-oophorectomy; and
  * Is at high risk for recurrence following treatment with curative intent surgery, ie: Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) 2009 surgical stage I/II with myometrial invasion of non-endometrioid histology; FIGO 2009 surgical stage I/II with myometrial invasion of any histology with known aberrant p53 expression or p53 mutation; or FIGO (2009) surgical stage III or IVA of any histology.
* Is disease-free with no evidence of loco-regional disease or distant metastasis post operatively and on imaging.
* Has not received any radiation or systemic therapy, including immunotherapy, hormonal therapy, or hyperthermic intraperitoneal chemotherapy (HIPEC), in any setting including the neoadjuvant setting for endometrial cancer (EC).
* Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before randomization.
* Submission of a tumor tissue sample from current diagnosis of Endometrial Carcinoma or Carcinosarcoma for prospective determination of histology and mismatch repair (MMR) status by central vendor is required for all participants.
* Has adequate organ function within 7 days of randomization.

Exclusion Criteria:

* Has recurrent endometrial carcinoma or carcinosarcoma.
* Has uterine mesenchymal tumor such as an endometrial stromal sarcoma, leiomyosarcoma, or other types of pure sarcomas. Adenosarcomas are also not allowed.
* Has FIGO (2009) Surgical Stage I/II EC of endometrioid histology without a known aberrant p53 expression or p53 mutation.
* Is known to have a deoxyribonucleic acid (DNA) polymerase epsilon catalytic subunit A (POLE) mutation.
* Has FIGO Stage IVB disease of any histology even if there is no evidence of disease after surgery.
* Has residual tumor whether measurable or non-measurable after surgery.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years.

  * Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers.
* 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 a live vaccine within 30 days before the first dose of study intervention.

  * Note: killed vaccines are allowed.
* Has a known intolerance to study intervention (or any of the excipients).
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.

  * Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
* Has any contraindication to the use of carboplatin or paclitaxel.
* 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 the first dose of study intervention.
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
* Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
* 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 HIV infection.
* Has a known history of Hepatitis B or known active Hepatitis C virus infection.
* 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 not recovered adequately from surgery and/or any complications from the surgery.
* Is breastfeeding.

Outcome Measures

Primary Outcomes

Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence

DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence, will be presented.

Time frame: Up to approximately 42 months

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to approximately 54 months

Secondary Outcomes

Disease-Free Survival (DFS) as Assessed Radiographically by Blinded Independent Central Review (BICR) or by Histopathologic Confirmation of Suspected Disease Recurrence

DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by BICR or by histopathologic confirmation of suspected disease recurrence, will be presented.

Time frame: Up to approximately 42 months

Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status

DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by CPS-determined PD-L1 status will be presented.

Time frame: Up to approximately 42 months

Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Combined Positivity Score (CPS)-Determined Programmed Cell Death 1 Ligand 1 (PD-L1) Status

OS is defined as the time from randomization to death due to any cause. The OS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by CPS-determined PD-L1 status will be presented.

Time frame: Up to approximately 54 months

Disease-Free Survival (DFS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status

DFS is defined as the time from randomization to the first documented local recurrence, distant metastasis, secondary systemic malignancy, or death due to any cause, whichever occurs first. The DFS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by tumor mutation burden (TMB) status, will be presented.

Time frame: Up to approximately 42 months

Overall Survival (OS) as Assessed Radiographically by Investigator or by Histopathologic Confirmation of Suspected Disease Recurrence by Tumor Mutation Burden (TMB) Status

OS is defined as the time from randomization to death due to any cause. The OS as assessed radiographically by investigator or by histopathologic confirmation of suspected disease recurrence by tumor mutation burden (TMB) status will be presented.

Time frame: Up to approximately 54 months

Number of Participants Who Experience One or More Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.

Time frame: Up to approximately 54 months

Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

Time frame: Up to approximately 52 weeks

Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status/Quality of Life (QoL) Score

The EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. Participant responses to questions 29 ("How would you rate your overall health during the past week?") and 30 ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). A higher score indicates a better overall health/quality of life status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined scores will be presented.

Time frame: Baseline and up to approximately 54 months

Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (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). 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.

Time frame: Baseline and up to approximately 54 months

Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Symptom Specific Scale for Endometrial Cancer (EORTC QLQ-EN24) Score

The EORTC-QLQ-EN24 is a 24-item questionnaire developed to be used in conjunction with the EORTC-QLQ-C30 to assess the quality of life of endometrial cancer patients. Participant responses are scored on a 4-point scale (1=not at all to 4=very much). A higher score indicates a better quality of life. The change from baseline in EORTC QLQ-E24 score will be presented.

Time frame: Baseline and up to approximately 54 months

Locations

University of Alabama - Birmingham ( Site 3061), Birmingham, United States

University of South Alabama, Mitchell Cancer Institute ( Site 3058), Mobile, United States

HonorHealth Research Institute - Biltmore ( Site 3043), Phoenix, United States

Arizona Oncology Associates PC- HOPE ( Site 3049), Tucson, United States

UCSD Moores Cancer Center ( Site 3053), La Jolla, United States

University Of Colorado ( Site 3051), Aurora, United States

Smilow Cancer Hospital at Yale New Haven ( Site 3070), New Haven, United States

Mount Sinai Cancer Center ( Site 3081), Miami Beach, United States

Northside Hospital ( Site 3036), Atlanta, United States

Northwestern Memorial Hospital ( Site 3044), Chicago, United States

Parkview Cancer Institute ( Site 3067), Fort Wayne, United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 3071), Indianapolis, United States

University of Iowa Hospital and Clinics ( Site 3046), Iowa City, United States

Norton Cancer Institute - St. Matthews ( Site 3056), Louisville, United States

WK Physicians Network/Gynecologic Oncology Associates ( Site 3047), Shreveport, United States

University of Massachusetts Medical School ( Site 3037), Worcester, United States

Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 3076), Mineola, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 3042), New York, United States

Montefiore Medical Center ( Site 3065), The Bronx, United States

Duke Cancer Center ( Site 3072), Durham, United States

Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 3080), Fargo, United States

The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C, Columbus, United States

Legacy Good Samaritan Medical Center ( Site 3033), Portland, United States

Sidney Kimmel Cancer Center - Jefferson Health ( Site 3078), Philadelphia, United States

AHN West Penn Hospital ( Site 3060), Pittsburgh, United States

Abington Hospital - Asplundh Cancer Center ( Site 3073), Willow Grove, United States

Sanford Gynecology Oncology ( Site 3045), Sioux Falls, United States

UT Southwestern Medical Center ( Site 3063), Dallas, United States

VCU Massey Cancer Center ( Site 3068), Richmond, United States

Centro de Oncología e Investigación de Buenos Aires ( Site 1005), Berazategui, Argentina

IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006), Caba, Argentina

Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003), Mar del Plata, Argentina

Hospital Britanico de Buenos Aires ( Site 1002), Buenos Aires, Argentina

Instituto de Oncologia de Rosario ( Site 1004), Rosario, Argentina

IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010), Buenos Aires, Argentina

Hospital Aleman ( Site 1001), Buenos Aires, Argentina

CEMIC ( Site 1009), Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 1007), La Rioja, Argentina

Medizinische Universitat Graz ( Site 2004), Graz, Austria

Medizinische Universitaet Innsbruck ( Site 2001), Innsbruck, Austria

Saint-Luc UCL ( Site 2042), Brussels, Belgium

C.I.U. Hopital Ambroise Pare ( Site 2039), Mons, Belgium

CHR Verviers ( Site 2035), Verviers, Belgium

OLV Ziekenhuis ( Site 2038), Aalst, Belgium

AZ Maria Middelares Gent ( Site 2032), Ghent, Belgium

Universitair Ziekenhuis Gent ( Site 2037), Ghent, Belgium

AZ Nikolaas ( Site 2031), Sint-Niklaas, Belgium

UZ Leuven ( Site 2040), Leuven, Belgium

AZ Groeninge ( Site 2036), Kortrijk, Belgium

CHC - Groupe Sante ( Site 2041), Liège, Belgium

CHU Liege Sart-Tilman ( Site 2044), Liège, Belgium

Tom Baker Cancer Centre ( Site 3007), Calgary, Canada

Kingston Health Sciences Centre ( Site 3003), Kingston, Canada

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 3006), Montreal, Canada

McGill University Health Centre ( Site 3005), Montreal, Canada

Centre intégré de cancérologie du CHU de Québec Université Laval, Hôpital de l'Enfant-Jésus ( Site 3, Québec, Canada

Fundacion Arturo Lopez Perez FALP ( Site 1062), Santiago, Chile

Centro de Cancer Nuestra Senora de la Esperanza ( Site 1063), Santiago, Chile

Bradfordhill-Clinical Area ( Site 1070), Santiago, Chile

Centro Investigación del Cáncer James Lind ( Site 1061), Temuco, Chile

Oncocentro ( Site 1065), Viña del Mar, Chile

Anhui Provincial Hospital-Obstetrics and Gynecology ( Site 4034), Hefei, China

Beijing Cancer Hospital ( Site 4048), Beijing, China

Peking Union Medical College Hospital ( Site 4036), Beijing, China

Chongqing Cancer Hospital ( Site 4040), Chongqing, China

The First Affiliated Hospital of Xiamen University ( Site 4060), Xiamen, China

The First Affiliated Hospital ( Site 4043), Guangzhou, China

Guangxi Medical University Affiliated Tumor Hospital ( Site 4049), Nanning, China

Harbin Medical University Cancer Hospital ( Site 4033), Harbin, China

Hubei Cancer Hospital ( Site 4059), Wuhan, China

Xiangya Hospital Central-South University ( Site 4035), Changsha, China

Hunan Cancer Hospital ( Site 4050), Changsha, China

Nanjing Drum Tower Hospital ( Site 4037), Nanjing, China

Jiangxi Maternal and Child Health Hospital ( Site 4051), Nanchang, China

The First Bethune Hospital of Jilin University ( Site 4057), Changchun, China

The First Affiliated Hospital of Xi an Jiaotong University ( Site 4045), Xi'an, China

Obstetrics and Gynecology Hosp. Fudan University ( Site 4041), Shanghai, China

Shanghai Renji Hospital Affiliated to Jiao Tong University ( Site 4053), Shanghai, China

Shanghai First Maternity and Infant Hospital-Gynecology department ( Site 4001), Shanghai, China

Sichuan Cancer Hospital ( Site 4039), Chengdu, China

Tianjin Medical University Cancer Institute & Hospital ( Site 4054), Tianjin, China

Yunnan Province Cancer Hospital-Gynecology Department ( Site 4055), Kunming, China

The First Affiliated Hospital, Zhejiang University-Gynecology ( Site 4002), Hangzhou, China

Women s Hospital School of Medicine Zhejiang University ( Site 4032), Hangzhou, China

The First Affiliated Hospital of Wenzhou Medical University ( Site 4056), Wenzhou, China

Clínica Vida Fundación - Sede Poblado ( Site 1096), Medellín, Colombia

Instituto Nacional de Cancerología E.S.E ( Site 1094), Bogotá, Colombia

Instituto Cancerologico de Narino Ltda ( Site 1092), Pasto, Colombia

Fundacion Valle del Lili ( Site 1093), Cali, Colombia

Fakultní nemocnice Brno Bohunice-Gynekologicko-porodnicka klinika ( Site 2394), Brno, Czechia

Fakultni nemocnice Kralovske Vinohrady ( Site 2393), Prague, Czechia

Vseobecna fakultni nemocnice v Praze ( Site 2391), Prague, Czechia

Fakultni nemocnice Olomouc ( Site 2392), Olomouc, Czechia

Rigshospitalet University Hospital ( Site 2515), Copehagen, Denmark

Herlev Hospital ( Site 2514), Herlev, Denmark

Aalborg Universitetshospital ( Site 2511), Aalborg, Denmark

Roskilde Sygehus ( Site 2513), Roskilde, Denmark

Odense Universitetshospital ( Site 2512), Odense, Denmark

Kuopio University Hospital ( Site 2543), Kuopio, Finland

Tampere University Hospital ( Site 2541), Tampere, Finland

Turku University Hospital ( Site 2542), Turku, Finland

Institut De Cancerologie De Lorraine ( Site 2072), Vandœuvre-lès-Nancy, France

Centre Antoine Lacassagne ( Site 2073), Nice, France

Centre Francois Baclesse ( Site 2062), Caen, France

Hôpital Privé Des Côtes d'Armor ( Site 2063), Plérin, France

CHU Besancon - Hopital Jean Minjoz ( Site 2068), Besançon, France

Institut Bergonie ( Site 2067), Bordeaux, France

Institut Universitaire du Cancer Toulouse - Oncopole ( Site 2065), Toulouse, France

Institut Regional du Cancer de Montpellier - ICM ( Site 2069), Montpellier, France

Hopital prive du Confluent ( Site 2061), Nantes, France

Centre Hospitalier Lyon Sud ( Site 2064), Pierre-Bénite, France

Hopital Cochin ( Site 2070), Paris, France

Gustave Roussy ( Site 2071), Villejuif, France

SLK-Kliniken Heilbronn GmbH ( Site 2116), Heilbronn, Germany

Klinikum Ludwigsburg ( Site 2111), Ludwigsburg, Germany

Universitaetsklinikum Tuebingen ( Site 2113), Tübingen, Germany

Medizinische Hochschule Hannover-Department of Obstetrics and Gynecology ( Site 2109), Hanover, Germany

Universitätsklinikum Bonn-Gynaecological oncology ( Site 2103), Bonn, Germany

Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung ( Site 2105), Essen, Germany

Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Frauenheilkunde und Gebur, Dresden, Germany

Universitätsklinikum Schleswig-Holstein ( Site 2101), Lübeck, Germany

General Hospital of Patras. St Andrews ( Site 2421), Pátrai, Greece

Geniko Panepistimako Nosokomeio ARETEIO ( Site 2423), Athens, Greece

Perifereiako Geniko Nosokomeio ALEXANDRA ( Site 2425), Athens, Greece

Athens University Hospital ATTIKON ( Site 2424), Chaïdári, Greece

Hospital Hygeia ( Site 2426), Marousi, Greece

Euromedica General Clinic of Thessaloniki ( Site 2422), Thessaloniki, Greece

Rambam Medical Center ( Site 2307), Haifa, Israel

Edith Wolfson Medical Center ( Site 2306), Holon, Israel

Hadassah Medical Center. Ein Kerem ( Site 2303), Jerusalem, Israel

Rabin Medical Center ( Site 2305), Petah Tikva, Israel

Chaim Sheba Medical Center ( Site 2301), Ramat Gan, Israel

Istittuto Nazionale dei Tumori Regina Elena IRCCS - IFO ( Site 2121), Roma, Italy

Fondazione Policlinico Universitario Agostino Gemelli ( Site 2124), Rome, Italy

Istituto di Candiolo - IRCCS ( Site 2125), Candiolo, Italy

Azienda Ospedaliera Spedali Civili di Brescia ( Site 2135), Brescia, Italy

IRCCS Ospedale San Raffaele ( Site 2130), Milan, Italy

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2122), Milan, Italy

Istituto Europeo di Oncologia IRCCS-Divisione di Ginecologia Oncologica ( Site 2132), Milan, Italy

Azienda Ospedaliera Universitaria Federico II ( Site 2123), Naples, Italy

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 2127), Naples, Italy

Istituto Oncologico Veneto IRCCS-Oncologia 2 ( Site 2134), Padua, Italy

Aichi Cancer Center Hospital ( Site 4190), Nagoya, Japan

National Cancer Center Hospital East ( Site 4197), Kashiwa, Japan

National Hospital Organization Shikoku Cancer Center ( Site 4181), Matsuyama, Japan

Ehime University Hospital ( Site 4187), Tōon, Japan

Kurume University Hospital ( Site 4186), Kurume, Japan

Gunma Prefectural Cancer Center ( Site 4183), Ōta, Japan

Hokkaido University Hospital ( Site 4194), Sapporo, Japan

Hyogo Cancer Center ( Site 4195), Akashi, Japan

Iwate Medical University Hospital ( Site 4189), Shiwa-gun, Japan

University of the Ryukyus Hospital ( Site 4184), Nakagami-gun, Japan

Saitama Medical University International Medical Center ( Site 4182), Hidaka, Japan

Shizuoka Cancer Center Hospital and Research Institute ( Site 4192), Sunto-gun, Japan

National Hospital Organization Kyushu Cancer Center ( Site 4193), Fukuoka, Japan

Niigata Cancer Center Hospital ( Site 4185), Niigata, Japan

Osaka International Cancer Institute ( Site 4188), Osaka, Japan

The Cancer Institute Hospital of JFCR ( Site 4196), Tokyo, Japan

Keio University Hospital ( Site 4191), Tokyo, Japan

Investigacion Onco Farmaceutica S de RL de CV ( Site 1127), La Paz, Mexico

Hospital San Lucas Cardiologica del Sureste ( Site 1122), Tuxtla Gutiérrez, Mexico

Instituto Nacional de Cancerologia ( Site 1124), Mexico City, Mexico

Christus Muguerza Clinica Vidriera ( Site 1125), Monterrey, Mexico

I Can Oncology Center SA de CV ( Site 1126), Monterrey, Mexico

Centro Oncologico Internacional. SEDNA ( Site 1121), Mexico City, Mexico

Hospital Angeles Roma ( Site 1123), Mexico City, Mexico

University Hospital of North Norway ( Site 2153), Tromsø, Norway

Soerlandet sykehus HF Kristiansand ( Site 2152), Kristiansand, Norway

Oslo Universitetssykehus Radiumhospitalet ( Site 2151), Oslo, Norway

Wielkopolskie Centrum Onkologii im.M.Sklodowskiej-Curie ( Site 2484), Poznan, Poland

Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 2487), Siedlce, Poland

Szpital Kliniczny im Ks Anny Mazowieckiej ( Site 2481), Warsaw, Poland

Bialostockie Centrum Onkologii ( Site 2483), Bialystok, Poland

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 2482), Gliwice, Poland

SPZOZ MSWIA z Warminsko-Mazurskim Centrum Onkologii w Olsztynie ( Site 2486), Olsztyn, Poland

Swietokrzyskie Centrum Onkologii SPZOZ ( Site 2485), Kielce, Poland

Arkhangelsk Clinical Oncological Dispensary ( Site 2637), Arkhangelsk, Russia

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 2645), Ufa, Russia

Chelyabinsk Regional Clinical Center Oncology and Nuclear Medicine ( Site 2644), Chelyabinsk, Russia

Krasnoyarsk Regional Clinical oncology dispensary ( Site 2643), Krasnoyarsk, Russia

National Research Ogarev Mordovia State University ( Site 2648), Saransk, Russia

FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 2634), Moscow, Russia

Moscow Research Oncology Institute named after P.A. Hertsen ( Site 2631), Moscow, Russia

Nizhegorodsky Regional Oncology Dispensary-chemotherapy department (Branch№1) ( Site 2639), Nizhny Novgorod, Russia

Samara Regional Clinical Oncology Center-Chemotherapy Dapartment ( Site 2649), Samara, Russia

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 2636), Saint Petersburg, Russia

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 2646), Kazan', Russia

Tomsk Scientific Research Institute of Oncology-Chemotherapy ( Site 2638), Tomsk, Russia

Yaroslavl Regional SBIH Clinical Oncology Hospital ( Site 2641), Yaroslavl, Russia

National Cancer Center ( Site 4065), Goyang-si, South Korea

Seoul National University Bundang Hospital ( Site 4063), Seongnam-si, South Korea

Severance Hospital Yonsei University Health System ( Site 4062), Seoul, South Korea

Asan Medical Center ( Site 4061), Seoul, South Korea

Samsung Medical Center ( Site 4064), Seoul, South Korea

Hospital Josep Trueta ( Site 2184), Girona, Spain

Clinica Universitaria de Navarra ( Site 2181), Madrid, Spain

Hospital Vall D Hebron ( Site 2182), Barcelona, Spain

Hospital Clinic i Provincial ( Site 2185), Barcelona, Spain

Hospital Universitario Reina Sofia ( Site 2183), Córdoba, Spain

Hospital Clinico San Carlos ( Site 2187), Madrid, Spain

Hospital Universitario La Paz ( Site 2186), Madrid, Spain

Karolinska Universitetssjukhuset Solna ( Site 2220), Solna, Sweden

Blod-och Tumorsjukdomar ( Site 2221), Uppsala, Sweden

Universitetssjukhuset i Linkoping. ( Site 2222), Linköping, Sweden

Changhua Christian Hospital ( Site 4095), Changhua, Taiwan

Taichung Veterans General Hospital ( Site 4094), Taichung, Taiwan

MacKay Memorial Hospital ( Site 4092), Taipei, Taiwan

Taipei Veterans General Hospital ( Site 4093), Taipei, Taiwan

Linkou Chang Gung Memorial Hospital ( Site 4091), Taoyuan District, Taiwan

Baskent Adana Dr Turgut Noyan Uygulama ve Arastirma Merkezi ( Site 2355), Adana, Turkey (Türkiye)

Cukurova Uni. Tip Fakultesi ( Site 2353), Adana, Turkey (Türkiye)

Baskent Universitesi Ankara Hastanesi ( Site 2354), Ankara, Turkey (Türkiye)

Ankara Universitesi Tıp Fakultesi Hastanesi ( Site 2350), Ankara, Turkey (Türkiye)

Medipol Universite Hastanesi ( Site 2352), Istanbul, Turkey (Türkiye)

Ege University Medical Faculty ( Site 2351), Izmir, Turkey (Türkiye)

I.E.U. Medical Point Hastanesi ( Site 2356), Izmir, Turkey (Türkiye)

Chernihiv Medical Center of Modern Oncology ( Site 2368), Chernihiv, Ukraine

Municipal Enterprise "Bukovinian сlinical oncology сenter" ( Site 2366), Chernivtsi, Ukraine

SO Grigoriev Institute for Medical Radiology and Oncology of NAMS of Ukraine ( Site 2363), Kharkiv, Ukraine

MNE "Khmelnytskyi regional antitumor center" ( Site 2365), Khmelnitskyi, Ukraine

LISOD - Israeli Oncological Hospital MedX-ray International Group, LLC ( Site 2364), Kiev, Ukraine

Lviv State Regional Oncological Center ( Site 2361), Lviv, Ukraine

The Municipal Enterprise Volyn Regional Medical Oncology Centre ( Site 2362), Lutsk, Ukraine

Bristol Haematology and Oncology Centre ( Site 2244), Bristol, United Kingdom

Castle Hill Hospital-Academic Oncology ( Site 2252), Cottingham, United Kingdom

Beatson West of Scotland Cancer Centre ( Site 2247), Glasgow, United Kingdom

UCLH NHS Foundation Trust ( Site 2242), London, United Kingdom

Royal Marsden NHS Foundation Trust ( Site 2248), London, United Kingdom

Royal Marsden Hospital Sutton-Surrey ( Site 2241), Sutton, United Kingdom

Leicester Royal Infirmary. Univ. Hosp. of Leicester NHS Trust ( Site 2249), Leicester, United Kingdom

The Christie Hospital NHS Foundation Trust ( Site 2243), Manchester, United Kingdom

Linked Diseases

Endometrial Neoplasms

Endometrial Neoplasms — a type of gynecological cancer.

Linked Papers

2024-09-14

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer

Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery. We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy. Patients were randomised to pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for six cycles added to carboplatin-paclitaxel followed by pembrolizumab 400 mg or placebo every 6 weeks (Q6W) for six cycles per treatment assignment. Radiotherapy was at the investigator's discretion. The primary endpoints were investigator-assessed disease-free survival (DFS) and overall survival in the intention-to-treat population. A total of 1095 patients were randomised (pembrolizumab, n = 545; placebo, n = 550). At this interim analysis (data cut-off, 4 March 2024), 119 (22%) DFS events occurred in the pembrolizumab group and 121 (22%) occurred in the placebo group [hazard ratio 1.02, 95% confidence interval (CI) 0.79-1.32; P = 0.570]. Kaplan-Meier estimates of 2-year DFS rates were 75% and 76% in the pembrolizumab and placebo groups, respectively. The hazard ratio for DFS was 0.31 (95% CI 0.14-0.69) in the dMMR population (n = 281) and 1.20 (95% CI 0.91-1.57) in the pMMR population (n = 814). Grade ≥3 adverse events (AEs) occurred in 386 of 543 (71%) and 348 of 549 (63%) patients in the pembrolizumab and placebo groups, respectively. No treatment-related grade 5 AEs occurred. Adjuvant pembrolizumab plus chemotherapy did not improve DFS in patients with newly diagnosed, high-risk, all-comer endometrial cancer. Preplanned subgroup analyses for stratification factors suggest that pembrolizumab plus chemotherapy improved DFS in patients with dMMR tumours. Safety was manageable. ClinicalTrials.gov, NCT04634877; EudraCT, 2020-003424-17. Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Study of Pembrolizumab (MK-3475) in Combination With Adjuvant Chemotherapy With or Without Radiotherapy in Participants With Newly Diagnosed Endometrial Cancer After Surgery With Curative Intent (MK-3475-B21 / KEYNOTE-B21 / ENGOT-en11 / GOG-3053)