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Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer

RecruitingPhase 3

A Randomized Phase III Trial of Carboplatin, Paclitaxel, Pembrolizumab Versus Carboplatin, Paclitaxel, Bevacizumab Versus Carboplatin, Paclitaxel, Pembrolizumab, Bevacizumab in the Treatment of pMMR, TP53 Mutated Advanced or Recurrent Endometrial Cancer

Who can join

Ages 18 and older · Women

Full eligibility criteria
Inclusion Criteria:

* Documentation of disease:

  * Stage III and stage IVA endometrial cancers (with measurable disease),
  * Stage IVB endometrial cancer (with or without measurable disease), or
  * Recurrent endometrial cancer (with or without measurable disease)
* In patients with measurable disease, lesions will be defined and monitored by RECIST 1.1. Measurable disease (RECIST 1.1) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI
* Histologic confirmation of the original primary tumor is required (submission of pathology report\[s\] is required). Patients with the following histologic types are eligible: endometrioid, serous, dedifferentiated/undifferentiated, clear cell, mixed epithelial, carcinosarcoma, adenocarcinoma not otherwise specified (N.O.S.)
* Patients must have:

  * Tumoral mismatch repair proficient (pMMR) disease as assessed by immunohistochemistry (IHC) AND
  * P53 IHC with aberrant staining pattern (aberrant p53 expression is consistent with mutant TP53). TP53 mutation by next-generation sequencing will also be accepted
* A pathology report demonstrating results of institutional MMR IHC and p53 IHC and/or TP53 by next-generation sequencing
* Patients may have received:

  * NO prior chemotherapy for treatment of endometrial cancer OR
  * Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\]) provided adjuvant chemotherapy was completed ≥ 12 months prior to registration
* Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to registration. For patients with recent radiation, they must have RECIST-evaluable disease outside of the radiation field and have recovered their marrow function
* Patients may have received prior hormonal (endocrine) therapy. All hormonal (endocrine) therapy must have been completed at least 1 week prior to registration
* NO prior pembrolizumab (or other anti-PD1, anti-PDL1 or anti-CTLA4 therapy) or bevacizumab (or other antiangiogenic therapy)
* Interval or cytoreductive surgery, after start of treatment on this trial, and prior to documentation of disease progression, is NOT permitted
* Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of disease progression. Patients with brain metastases must have follow up imaging demonstrating no evidence of disease progression and that the disease is stable off of steroids
* Age ≥ 18
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
* Not pregnant and not nursing
* Absolute neutrophil count (ANC) ≥ 1,500 cells/mm\^3
* Platelets ≥ 100,000 cells/mm\^3
* Hemoglobin ≥ 8 g/dl
* Creatinine clearance (CrCl) of ≥ 30 mL/min by the Cockcroft-Gault formula
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x institutional ULN may be enrolled)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x institutional ULN
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
* No active infection requiring parenteral antibiotics
* No current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
* No clinically significant bleeding within 28 days prior to registration
* No uncontrolled hypertension, defined as systolic ≥ 160 mm Hg or diastolic ≥ 100 mm Hg
* No major surgery within 28 days of initiation of bevacizumab
* No active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including corticosteroids. This includes, but is not limited to, patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome because of the risk of recurrence or exacerbation of disease

  * Patients with vitiligo, endocrine deficiencies including type I diabetes mellitus, thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible
  * Topical or inhaled steroids are allowed
  * Patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), and anti-thyroid antibodies should be evaluated with the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible
* No history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
* No history of stem cell or solid organ transplant
* No history of allergic reaction to the study agent(s) or compounds of similar chemical or biologic composition to the study agent(s) (or any of its excipients)

About the study

This phase III trial compares the effect of bevacizumab in combination with carboplatin, paclitaxel and pembrolizumab to the usual treatments of carboplatin and paclitaxel with or without pembrolizumab in treating patients with stage III, IVA or IVB mismatch repair protein proficient (pMMR) and TP53 mutated endometrial cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has come back after a period of improvement (recurrent). Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Adding bevacizumab to the combination of carboplatin, paclitaxel and pembrolizumab may be more effective than the usual treatment combinations of carboplatin and paclitaxel with or without pembrolizumab in treating patients with advanced or recurrent pMMR and TP53 mutated endometrial cancer.

What is being tested

Sponsor: National Cancer Institute (NCI) · Participants: 255 · Started: Jan 27, 2026

Contact the study team

Official record on ClinicalTrials.gov — NCT07198074

Locations in the U.S.

AlabamaUniversity of Alabama at Birmingham Cancer Center, Birmingham
AlaskaAlaska Women's Cancer Care, Anchorage
ArizonaCancer Center at Saint Joseph's, Phoenix
Banner University Medical Center - Tucson, Tucson
University of Arizona Cancer Center-North Campus, Tucson
ArkansasHighlands Oncology Group - Fayetteville, Fayetteville
University of Arkansas for Medical Sciences, Little Rock
Highlands Oncology Group - Rogers, Rogers
Highlands Oncology Group, Springdale
CaliforniaMercy Cancer Center - Carmichael, Carmichael
Mercy San Juan Medical Center, Carmichael
Kaiser Permanente Dublin, Dublin
Mercy Cancer Center - Elk Grove, Elk Grove
Kaiser Permanente-Fremont, Fremont
Kaiser Permanente Fresno Orchard Plaza, Fresno
Cedars-Sinai Medical Center, Los Angeles
Los Angeles General Medical Center, Los Angeles
USC / Norris Comprehensive Cancer Center, Los Angeles
Kaiser Permanente- Modesto MOB II, Modesto
Kaiser Permanente-Oakland, Oakland
Stanford Cancer Institute Palo Alto, Palo Alto
Eisenhower Medical Center, Rancho Mirage
Mercy Cancer Center - Rocklin, Rocklin
Kaiser Permanente-Roseville, Roseville
Kaiser Permanente Downtown Commons, Sacramento
Kaiser Permanente-South Sacramento, Sacramento
Mercy Cancer Center - Sacramento, Sacramento
University of California Davis Comprehensive Cancer Center, Sacramento
Kaiser Permanente-San Francisco, San Francisco
Kaiser Permanente-Santa Teresa-San Jose, San Jose
Kaiser Permanente San Leandro, San Leandro
Kaiser San Rafael-Gallinas, San Rafael
Kaiser Permanente Medical Center - Santa Clara, Santa Clara
Kaiser Permanente-Santa Rosa, Santa Rosa
Kaiser Permanente-South San Francisco, South San Francisco
Kaiser Permanente-Vallejo, Vallejo
Kaiser Permanente-Walnut Creek, Walnut Creek
Woodland Memorial Hospital, Woodland
ColoradoUCHealth University of Colorado Hospital, Aurora
Memorial Hospital North, Colorado Springs
UCHealth Memorial Hospital Central, Colorado Springs
Cancer Care and Hematology-Fort Collins, Fort Collins
Poudre Valley Hospital, Fort Collins
UCHealth Greeley Hospital, Greeley
UCHealth Highlands Ranch Hospital, Highlands Ranch
Medical Center of the Rockies, Loveland
ConnecticutHartford Hospital, Hartford
Hartford HealthCare - Manchester, Manchester
The Hospital of Central Connecticut, New Britain
DelawareBeebe South Coastal Health Campus, Millville
Helen F Graham Cancer Center, Newark
Medical Oncology Hematology Consultants PA, Newark
Beebe Health Campus, Rehoboth Beach
District of ColumbiaMedStar Washington Hospital Center, Washington D.C.
FloridaSarasota Memorial Hospital-Venice, N. Venice
FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery, Sarasota
Florida Cancer Specialists - Sarasota Downtown, Sarasota
Sarasota Memorial Health Care Center at University Parkway, Sarasota
Sarasota Memorial Hospital, Sarasota
Florida Cancer Specialists - Venice Pinebrook, Venice
GeorgiaEmory University Hospital Midtown, Atlanta
Emory University Hospital/Winship Cancer Institute, Atlanta
Grady Health System, Atlanta
Augusta University Medical Center, Augusta
Emory Decatur Hospital, Decatur
HawaiiKaiser Permanente Moanalua Medical Center, Honolulu
IdahoKootenai Health - Coeur d'Alene, Coeur d'Alene
Kootenai Clinic Cancer Services - Post Falls, Post Falls
Kootenai Clinic Cancer Services - Sandpoint, Sandpoint
IllinoisNorthwestern University, Chicago
Rush MD Anderson Cancer Center, Chicago
University of Chicago Comprehensive Cancer Center, Chicago
Carle at The Riverfront, Danville
Northwestern Medicine Cancer Center Kishwaukee, DeKalb
Cancer Care Specialists of Illinois - Decatur, Decatur
Decatur Memorial Hospital, Decatur
Carle Physician Group-Effingham, Effingham
NorthShore University HealthSystem-Evanston Hospital, Evanston
Northwestern Medicine Cancer Center Delnor, Geneva
NorthShore University HealthSystem-Glenbrook Hospital, Glenview
Ingalls Memorial Hospital, Harvey
NorthShore University HealthSystem-Highland Park Hospital, Highland Park
Carle Physician Group-Mattoon/Charleston, Mattoon
UC Comprehensive Cancer Center at Silver Cross, New Lenox
Carle BroMenn Medical Center, Normal
Carle Cancer Institute Normal, Normal
Cancer Care Center of O'Fallon, O'Fallon
HSHS Saint Elizabeth's Hospital, O'Fallon
Northwestern Medicine Oak Brook, Oak Brook
Rush MD Anderson Cancer Center at Rush Oak Park, Oak Park
Northwestern Medicine Orland Park, Orland Park
University of Chicago Medicine-Orland Park, Orland Park
OSF Saint Francis Medical Center, Peoria
Southern Illinois University School of Medicine, Springfield
Springfield Clinic, Springfield
Springfield Memorial Hospital, Springfield
Carle Cancer Center, Urbana
Northwestern Medicine Cancer Center Warrenville, Warrenville
IndianaUChicago Medicine Northwest Indiana, Crown Point
Goshen Center for Cancer Care, Goshen
Ascension Saint Vincent Indianapolis Hospital, Indianapolis
IowaUI Health Care Mission Cancer and Blood - Ankeny Clinic, Ankeny
Saint Anthony Regional Hospital, Carroll
Mercy Hospital, Cedar Rapids
Oncology Associates at Mercy Medical Center, Cedar Rapids
UI Health Care Mission Cancer and Blood - West Des Moines Clinic, Clive
Broadlawns Medical Center, Des Moines
Iowa Methodist Medical Center, Des Moines
Mercy Medical Center - Des Moines, Des Moines
UI Health Care Mission Cancer and Blood - Des Moines Clinic, Des Moines
UI Health Care Mission Cancer and Blood - Laurel Clinic, Des Moines
UI Healthcare Mission Cancer and Blood - Fort Dodge, Fort Dodge
University of Iowa/Holden Comprehensive Cancer Center, Iowa City
UI Health Care Mission Cancer and Blood - Waukee Clinic, Waukee
KentuckyBaptist Health Lexington, Lexington
University of Kentucky/Markey Cancer Center, Lexington
LouisianaWest Jefferson Medical Center, Marrero
East Jefferson General Hospital, Metairie
LSU Healthcare Network / Metairie Multi-Specialty Clinic, Metairie
University Medical Center New Orleans, New Orleans
MaineLafayette Family Cancer Center-EMMC, Brewer
MaineHealth Maine Medical Center- Scarborough, Scarborough
MarylandJohns Hopkins University/Sidney Kimmel Cancer Center, Baltimore
MedStar Franklin Square Medical Center/Weinberg Cancer Institute, Baltimore
MassachusettsDana-Farber Cancer Institute, Boston
MichiganUniversity of Michigan Rogel Cancer Center, Ann Arbor
Bronson Battle Creek, Battle Creek
Trinity Health IHA Medical Group Hematology Oncology - Brighton, Brighton
University of Michigan - Brighton Center for Specialty Care, Brighton
Trinity Health IHA Medical Group Hematology Oncology - Canton, Canton
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital, Chelsea
Wayne State University/Karmanos Cancer Institute, Detroit
OSF Saint Francis Hospital and Medical Group, Escanaba
Weisberg Cancer Treatment Center, Farmington Hills
Cancer Hematology Centers - Flint, Flint
Genesys Hurley Cancer Institute, Flint
Hurley Medical Center, Flint
Corewell Health Grand Rapids Hospitals - Butterworth Hospital, Grand Rapids
Trinity Health Grand Rapids Hospital, Grand Rapids
Bronson Methodist Hospital, Kalamazoo
West Michigan Cancer Center, Kalamazoo
University of Michigan Health - Sparrow Lansing, Lansing
Trinity Health Saint Mary Mercy Livonia Hospital, Livonia
Trinity Health Muskegon Hospital, Muskegon
Corewell Health Lakeland Hospitals - Niles Hospital, Niles
Cancer and Hematology Centers of Western Michigan - Norton Shores, Norton Shores
Trinity Health Saint Joseph Mercy Oakland Hospital, Pontiac
Corewell Health Reed City Hospital, Reed City
Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center, Saint Joseph
Corewell Health Lakeland Hospitals - Saint Joseph Hospital, Saint Joseph
Munson Medical Center, Traverse City
University of Michigan Health - West, Wyoming
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus, Ypsilanti
MinnesotaEssentia Health Saint Joseph's Medical Center, Brainerd
Mercy Hospital, Coon Rapids
Essentia Health - Deer River Clinic, Deer River
Essentia Health Cancer Center, Duluth
Fairview Southdale Hospital, Edina
Minnesota Oncology - Edina, Edina
Essentia Health Hibbing Clinic, Hibbing
Abbott-Northwestern Hospital, Minneapolis
Park Nicollet Clinic - Saint Louis Park, Saint Louis Park
Regions Hospital, Saint Paul
United Hospital, Saint Paul
Essentia Health Sandstone, Sandstone
Essentia Health Virginia Clinic, Virginia
Minnesota Oncology Hematology PA-Woodbury, Woodbury
MissouriMU Health - University Hospital/Ellis Fischel Cancer Center, Columbia
CoxHealth South Hospital, Springfield
Mercy Hospital Springfield, Springfield
Washington University School of Medicine, St Louis
MontanaCommunity Hospital of Anaconda, Anaconda
Billings Clinic Cancer Center, Billings
Intermountain Health West End Clinic, Billings
Saint Vincent Frontier Cancer Center, Billings
Bozeman Health Deaconess Hospital, Bozeman
Benefis Sletten Cancer Institute, Great Falls
Logan Health Medical Center, Kalispell
Community Medical Center, Missoula
NebraskaNebraska Medicine-Bellevue, Bellevue
Fred and Pamela Buffett Cancer Center - Kearney, Kearney
Nebraska Medicine-Village Pointe, Omaha
Nebraska Methodist Hospital, Omaha
University of Nebraska Medical Center, Omaha
NevadaWomen's Cancer Center of Nevada, Las Vegas
New JerseyMemorial Sloan Kettering Basking Ridge, Basking Ridge
Cooperman Barnabas Medical Center, Livingston
Memorial Sloan Kettering Monmouth, Middletown
Memorial Sloan Kettering Bergen, Montvale
Rutgers Cancer Institute of New Jersey, New Brunswick
Rutgers New Jersey Medical School, Newark
The Valley Hospital - Luckow Pavilion, Paramus
Valley Health System Ridgewood Campus, Ridgewood
Sidney Kimmel Cancer Center Washington Township, Sewell
New MexicoUniversity of New Mexico Cancer Center, Albuquerque
New YorkNorthwell Health Imbert Cancer Center, Bay Shore
Memorial Sloan Kettering Commack, Commack
Northwell Health Physician Partners at Flushing, Flushing
Northwell Health Cancer Institute at Huntington, Greenlawn
Memorial Sloan Kettering Westchester, Harrison
Northwell Health/Center for Advanced Medicine, Lake Success
Lenox Hill Hospital, New York
Manhattan Eye Ear and Throat Hospital, New York
Memorial Sloan Kettering Cancer Center, New York
Mount Sinai Chelsea, New York
Mount Sinai Hospital, New York
Mount Sinai West, New York
Queens Cancer Center, Rego Park
University of Rochester, Rochester
Phelps Memorial Hospital Center, Sleepy Hollow
Staten Island University Hospital, Staten Island
Stony Brook University Medical Center, Stony Brook
State University of New York Upstate Medical University, Syracuse
Montefiore Medical Center - Moses Campus, The Bronx
Montefiore Medical Center-Einstein Campus, The Bronx
Montefiore Medical Center-Weiler Hospital, The Bronx
Memorial Sloan Kettering Nassau, Uniondale
Wilmot Cancer Institute at Webster, Webster
North CarolinaUNC Lineberger Comprehensive Cancer Center, Chapel Hill
Southeastern Medical Oncology Center-Clinton, Clinton
Duke University Medical Center, Durham
Southeastern Medical Oncology Center-Goldsboro, Goldsboro
Southeastern Medical Oncology Center-Jacksonville, Jacksonville
Duke Women's Cancer Care Raleigh, Raleigh
North DakotaEssentia Health Cancer Center-South University Clinic, Fargo
OhioOhioHealth O'Bleness Hospital, Athens
UHHS-Chagrin Highlands Medical Center, Beachwood
Aultman Health Foundation, Canton
Geauga Hospital, Chardon
Case Western Reserve University, Cleveland
Columbus Oncology and Hematology Associates Inc, Columbus
Doctors Hospital, Columbus
Grant Medical Center, Columbus
Ohio State University Comprehensive Cancer Center, Columbus
Riverside Methodist Hospital, Columbus
Delaware Health Center-Grady Cancer Center, Delaware
Grady Memorial Hospital, Delaware
Columbus Oncology and Hematology Associates, Dublin
Dublin Methodist Hospital, Dublin
OhioHealth Mansfield Hospital, Mansfield
OhioHealth Marion General Hospital, Marion
UH Seidman Cancer Center at Lake Health Mentor Campus, Mentor
University Hospitals Parma Medical Center, Parma
OhioHealth Pickerington Methodist Hospital, Pickerington
ProMedica Flower Hospital, Sylvania
OhioHealth Westerville Medical Campus/Westerville Cancer Center, Westerville
UH Seidman Cancer Center at Saint John Medical Center, Westlake
OklahomaUniversity of Oklahoma Health Sciences Center, Oklahoma City
OregonLegacy Good Samaritan Hospital and Medical Center, Portland
Providence Portland Medical Center, Portland
Providence Saint Vincent Medical Center, Portland
Legacy Meridian Park Hospital, Tualatin
PennsylvaniaUPMC Hillman Cancer Center Erie, Erie
UPMC Cancer Centers - Arnold Palmer Pavilion, Greensburg
Penn State Milton S Hershey Medical Center, Hershey
UPMC Hillman Cancer Center at Rocco And Nancy Ortenzio Cancer Pavilion, Mechanicsburg
Jefferson Torresdale Hospital, Philadelphia
Thomas Jefferson University Hospital, Philadelphia
UPMC-Magee Womens Hospital, Pittsburgh
UPMC-Passavant Hospital, Pittsburgh
UPMC Cancer Center-Washington, Washington
Asplundh Cancer Pavilion, Willow Grove
Rhode IslandRhode Island Hospital, Providence
Women and Infants Hospital, Providence
TennesseeVanderbilt-Ingram Cancer Center Cool Springs, Franklin
Vanderbilt Breast Center at One Hundred Oaks, Nashville
Vanderbilt University/Ingram Cancer Center, Nashville
UtahHuntsman Cancer Institute/University of Utah, Salt Lake City
University of Utah Sugarhouse Health Center, Salt Lake City
South Jordan Health Center, South Jordan
VirginiaUniversity of Virginia Cancer Center, Charlottesville
VCU Massey Comprehensive Cancer Center, Richmond
WashingtonSwedish Cancer Institute-Edmonds, Edmonds
Swedish Cancer Institute-Issaquah, Issaquah
Swedish Medical Center-First Hill, Seattle
Legacy Salmon Creek Hospital, Vancouver
West VirginiaUnited Hospital Center, Bridgeport
West Virginia University Charleston Division, Charleston
WVUH-Berkely Medical Center, Martinsburg
West Virginia University Healthcare, Morgantown
Camden Clark Medical Center, Parkersburg
WisconsinDuluth Clinic Ashland, Ashland
Saint Vincent Hospital Cancer Center Green Bay, Green Bay
Saint Vincent Hospital Cancer Center at Saint Mary's, Green Bay
Gundersen Lutheran Medical Center, La Crosse
Medical College of Wisconsin, Milwaukee
Saint Vincent Hospital Cancer Center at Oconto Falls, Oconto Falls
Saint Vincent Hospital Cancer Center at Sheboygan, Sheboygan
Sheboygan Physicians Group, Sheboygan
Essentia Health-Spooner Clinic, Spooner
Saint Vincent Hospital Cancer Center at Sturgeon Bay, Sturgeon Bay
Essentia Health Saint Mary's Hospital - Superior, Superior

Conditions

From ClinicalTrials.gov, data retrieved Sep 29, 2026. Each study sets its own eligibility; the study team decides who can join.