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Adding bevacizumab to carboplatin, paclitaxel and pembrolizumab for pMMR, TP53‑mutated advanced or recurrent 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

Phase 3 Interventional National Cancer Institute (NCI) · NCT07198074

This trial tests whether adding bevacizumab to carboplatin and paclitaxel with pembrolizumab helps people with pMMR, TP53‑mutated advanced or recurrent endometrial cancer live longer without the disease getting worse.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment255 (estimated)
Ages18 Years and up
SexFemale
SponsorNational Cancer Institute (NCI) NIH
Drugs / interventionspembrolizumab, bevacizumab, chemotherapy, radiation, Immunotherapy
Locations184 sites (Birmingham, Alabama and 183 other locations)
Trial IDNCT07198074 on ClinicalTrials.gov

What this trial studies

This is a phase III, randomized NCI‑sponsored trial comparing the combination of bevacizumab with carboplatin, paclitaxel, and pembrolizumab against standard regimens of carboplatin and paclitaxel with or without pembrolizumab. The primary endpoint is progression‑free survival, with overall survival, toxicity (CTCAE v5.0), and objective response rate as key secondary endpoints. The trial includes biomarker-driven analyses by p53 IHC pattern and mutation type and requires imaging assessments per RECIST 1.1 for patients with measurable disease. Biospecimens will be collected to support correlative studies and further molecular characterization.

Who should consider this trial

Good fit: Ideal candidates are adults with stage III, IVA, IVB, or recurrent endometrial cancer whose tumors are mismatch repair protein proficient (pMMR) and have a TP53 mutation, with eligible histologies such as endometrioid, serous, clear cell, carcinosarcoma, or mixed epithelial types.

Not a fit: Patients whose tumors are mismatch repair deficient (dMMR), lack TP53 mutation, have early‑stage disease only, or who have contraindications to bevacizumab or platinum/taxane chemotherapy (for example uncontrolled hypertension, recent major bleeding, or poor wound healing) may not benefit from this regimen.

Why it matters

Potential benefit: If successful, adding bevacizumab could delay disease progression and potentially extend survival for patients with pMMR, TP53‑mutated advanced or recurrent endometrial cancer.

How similar studies have performed: Anti‑VEGF drugs plus chemotherapy and single‑agent pembrolizumab have shown activity in gynecologic cancers and immunotherapy has proven benefit in some endometrial settings, but combining bevacizumab with both chemotherapy and pembrolizumab in pMMR, TP53‑mutated endometrial cancer is relatively novel and not yet established in phase III results.

Eligibility criteria

Show full inclusion / exclusion 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)

Where this trial is running

Birmingham, Alabama and 183 other locations

+134 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Advanced Endometrial CarcinomaRecurrent Endometrial Carcinoma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.