Testing the Addition of an Antiangiogenic Drug (Bevacizumab) to Chemotherapy (Carboplatin and Paclitaxel) Combined With Immunotherapy (Pembrolizumab) for pMMR, TP53 Mutated Endometrial Cancer
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
- Advanced Endometrial Carcinoma
- Recurrent Endometrial Carcinoma
At a glance
- Phase
- Phase 3
- Study type
- Interventional
- Sponsor
- National Cancer Institute (NCI)
- Enrolment target
- 255
- Started
- 27 January 2026
- Main results due
- 1 July 2028
- Study sites
- 294
- Registry updated
- 29 September 2026
Can you take part?
- Aged 18 years and over.
- Women only.
- You need the condition being studied — healthy volunteers are not accepted.
These are the headline rules only. Every study has a longer list, and whether you are eligible is decided by the research team at the site — never by this page.
Read the 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)
What this study is about
In the sponsor’s own words, from the registry.
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.
Study sites(294)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Recruiting
Alaska Women's Cancer Care
Anchorage, Alaska, United States
Recruiting
Cancer Center at Saint Joseph's
Phoenix, Arizona, United States
Recruiting
Banner University Medical Center - Tucson
Tucson, Arizona, United States
Recruiting
University of Arizona Cancer Center-North Campus
Tucson, Arizona, United States
Recruiting
Highlands Oncology Group - Fayetteville
Fayetteville, Arkansas, United States
Recruiting
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Recruiting
Highlands Oncology Group - Rogers
Rogers, Arkansas, United States
Recruiting
Highlands Oncology Group
Springdale, Arkansas, United States
Recruiting
Mercy Cancer Center - Carmichael
Carmichael, California, United States
Recruiting
Mercy San Juan Medical Center
Carmichael, California, United States
Recruiting
Kaiser Permanente Dublin
Dublin, California, United States
Recruiting
Mercy Cancer Center - Elk Grove
Elk Grove, California, United States
Recruiting
Kaiser Permanente-Fremont
Fremont, California, United States
Recruiting
Kaiser Permanente Fresno Orchard Plaza
Fresno, California, United States
Recruiting
Los Angeles General Medical Center
Los Angeles, California, United States
Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Recruiting
Cedars-Sinai Medical Center
Los Angeles, California, United States
Recruiting
Kaiser Permanente- Modesto MOB II
Modesto, California, United States
Recruiting
Kaiser Permanente-Oakland
Oakland, California, United States
Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Recruiting
Eisenhower Medical Center
Rancho Mirage, California, United States
Recruiting
Mercy Cancer Center - Rocklin
Rocklin, California, United States
Recruiting
Kaiser Permanente-Roseville
Roseville, California, United States
Recruiting
Kaiser Permanente Downtown Commons
Sacramento, California, United States
Recruiting
Mercy Cancer Center - Sacramento
Sacramento, California, United States
Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
Recruiting
Kaiser Permanente-South Sacramento
Sacramento, California, United States
Recruiting
Kaiser Permanente-San Francisco
San Francisco, California, United States
Recruiting
Kaiser Permanente-Santa Teresa-San Jose
San Jose, California, United States
Recruiting
Kaiser Permanente San Leandro
San Leandro, California, United States
Recruiting
Kaiser San Rafael-Gallinas
San Rafael, California, United States
Recruiting
Kaiser Permanente Medical Center - Santa Clara
Santa Clara, California, United States
Recruiting
Kaiser Permanente-Santa Rosa
Santa Rosa, California, United States
Recruiting
Kaiser Permanente-South San Francisco
South San Francisco, California, United States
Recruiting
Kaiser Permanente-Vallejo
Vallejo, California, United States
Recruiting
Kaiser Permanente-Walnut Creek
Walnut Creek, California, United States
Recruiting
Woodland Memorial Hospital
Woodland, California, United States
Recruiting
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Recruiting
UCHealth Memorial Hospital Central
Colorado Springs, Colorado, United States
Recruiting
Memorial Hospital North
Colorado Springs, Colorado, United States
Recruiting
Poudre Valley Hospital
Fort Collins, Colorado, United States
Recruiting
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado, United States
Recruiting
UCHealth Greeley Hospital
Greeley, Colorado, United States
Recruiting
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, United States
Recruiting
Medical Center of the Rockies
Loveland, Colorado, United States
Recruiting
Hartford Hospital
Hartford, Connecticut, United States
Recruiting
Hartford HealthCare - Manchester
Manchester, Connecticut, United States
Recruiting
The Hospital of Central Connecticut
New Britain, Connecticut, United States
Recruiting
Beebe South Coastal Health Campus
Millville, Delaware, United States
Recruiting
Helen F Graham Cancer Center
Newark, Delaware, United States
Recruiting
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States
Recruiting
Beebe Health Campus
Rehoboth Beach, Delaware, United States
Recruiting
MedStar Washington Hospital Center
Washington D.C., District of Columbia, United States
Recruiting
Sarasota Memorial Hospital-Venice
N. Venice, Florida, United States
Recruiting
Florida Cancer Specialists - Sarasota Downtown
Sarasota, Florida, United States
Recruiting
FPG - Surgical Oncology Clinics Gynecologic Oncology Surgery
Sarasota, Florida, United States
Recruiting
Sarasota Memorial Hospital
Sarasota, Florida, United States
Recruiting
Sarasota Memorial Health Care Center at University Parkway
Sarasota, Florida, United States
Recruiting
Florida Cancer Specialists - Venice Pinebrook
Venice, Florida, United States
Recruiting
Showing 60 of 294 sites — filter to narrow it down. 292 of the 294 sites on this study are recruiting right now — a site can stop enrolling while the study as a whole is still open.
Source: ClinicalTrials.gov record NCT07198074. Trialion does not run this study, is not paid to refer anyone to it, and cannot enrol you. Eligibility is always decided by the research team at the site.
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