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Clinical Trials in the USA / NCT04634877
Active, not recruiting Phase 3

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)

NCT04634877 · tracked via the Priya Life Science USA tracker
Sponsor
Merck Sharp & Dohme LLC
Phase
Phase 3
Started
2021-01-10
Last updated
2026-07-24

Condition(s) studied

Endometrial Neoplasms

Investigational drug(s) / intervention(s)

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

Pembrolizumab: IV infusion

Carboplatin: IV infusion

Paclitaxel: IV infusion

Placebo for pembrolizumab: IV infusion

Docetaxel: IV infusion docetaxel 75 mg/m\^2 Q3W or 25 mg/m2 QW may be given in place of paclitaxel following sponsor consultation if a participant experiences severe hypersensitivity to paclitaxel or an adverse event requiring discontinuation of paclitaxel.

Cisplatin: Cisplatin 75 mg/m\^2 IV infusion Q3W may be given in place of carboplatin following sponsor consultation if a participant experiences severe hypersensitivity to carboplatin or an adverse event requiring discontinuation of carboplatin.

External Beam Radiotherapy (EBRT): ≥4500 cGY given according to local practice, at the discretion of the investigator

Cisplatin (as radiosensitizer): If a participant receives external beam radiotherapy (EBRT), then cisplatin 50 mg/m\^2 IV infusion may be administered as a radiosensitizer at the discretion of the investigator, on days 1 and 29

Brachytherapy: Given according to local practice, at the discretion of the investigator

Study 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.

Eligibility

Sex
FEMALE
Min age
18 Years
Max age
Healthy volunteers
No
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.

Primary outcome measure(s)

Trial sites (231)

FacilityCityRegionStatus
University of Alabama - Birmingham ( Site 3061) Birmingham Alabama
University of South Alabama, Mitchell Cancer Institute ( Site 3058) Mobile Alabama
HonorHealth Research Institute - Biltmore ( Site 3043) Phoenix Arizona
Arizona Oncology Associates PC- HOPE ( Site 3049) Tucson Arizona
UCSD Moores Cancer Center ( Site 3053) La Jolla California
University Of Colorado ( Site 3051) Aurora Colorado
Smilow Cancer Hospital at Yale New Haven ( Site 3070) New Haven Connecticut
Mount Sinai Cancer Center ( Site 3081) Miami Beach Florida
Northside Hospital ( Site 3036) Atlanta Georgia
Northwestern Memorial Hospital ( Site 3044) Chicago Illinois
Parkview Cancer Institute ( Site 3067) Fort Wayne Indiana
Indiana University Melvin and Bren Simon Cancer Center ( Site 3071) Indianapolis Indiana
University of Iowa Hospital and Clinics ( Site 3046) Iowa City Iowa
Norton Cancer Institute - St. Matthews ( Site 3056) Louisville Kentucky
WK Physicians Network/Gynecologic Oncology Associates ( Site 3047) Shreveport Louisiana
University of Massachusetts Medical School-Division of Gynecologic Oncology ( Site 3037) Worcester Massachusetts
Perlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 3076) Mineola New York
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 3042) New York New York
Montefiore Medical Center ( Site 3065) The Bronx New York
Duke Cancer Center ( Site 3072) Durham North Carolina
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 3080) Fargo North Dakota
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 3066) Columbus Ohio
Legacy Good Samaritan Medical Center ( Site 3033) Portland Oregon
Sidney Kimmel Cancer Center - Jefferson Health ( Site 3078) Philadelphia Pennsylvania
AHN West Penn Hospital ( Site 3060) Pittsburgh Pennsylvania
Abington Hospital - Asplundh Cancer Center ( Site 3073) Willow Grove Pennsylvania
Sanford Gynecology Oncology ( Site 3045) Sioux Falls South Dakota
UT Southwestern Medical Center ( Site 3063) Dallas Texas
VCU Massey Cancer Center ( Site 3068) Richmond Virginia
Centro de Oncología e Investigación de Buenos Aires ( Site 1005) Berazategui Buenos Aires
IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 1006) CABA Buenos Aires
CEMIC ( Site 1009) CABA Buenos Aires
Hospital Britanico de Buenos Aires ( Site 1002) Ciudad Autónoma de Buenos Aires Buenos Aires
Instituto de Investigaciones Clinicas Mar del Plata ( Site 1003) Mar del Plata Buenos Aires
Instituto de Oncologia de Rosario ( Site 1004) Rosario Santa Fe Province
IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 1010) Buenos Aires Argentina
Hospital Aleman ( Site 1001) Buenos Aires Argentina
Centro Oncologico Riojano Integral ( Site 1007) La Rioja Argentina
Medizinische Universitat Graz ( Site 2004) Graz Styria
Medizinische Universitaet Innsbruck ( Site 2001) Innsbruck Tyrol

+ 191 more sites — see the full list on the official registry below.

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04634877 on ClinicalTrials.gov ↗ ← All trials in the USA