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.
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
None
Parallel
Bevacizumab
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo urine and blood sample collection
Carboplatin
DrugGiven IV
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Paclitaxel
DrugGiven IV
Pembrolizumab
Biological/VaccineGiven IV
Progression-free survival (PFS)
Will be defined using Response Evaluation Criteria in Solid Tumors version (v) 1.1. Will be tested using one-sided log-rank tests with α-levels stratified by factors used in the randomization. Patients will be grouped by their randomized treatment assignment for intention-to-treat (ITT) analyses, supported by patients in ITT population. Treatment hazard ratios and their 95% confidence intervals will be estimated using a Cox proportional hazards models specified with a main effect for the randomized treatment assignment and stratified using the stratification factors applied at randomization.
Overall survival (OS)
Will be assessed with proportional hazards modeling stratified for stratification factors at baseline. Hazard ratios and corresponding 2-sided 95% confidence intervals will be estimated for treatment (with Arm 1 as the reference arm).
Prognostic and predictive associations of type of TP53 mutation status with PFS
Will be assessed with proportional hazards modeling stratified for stratification factors at baseline and adjusted by randomized treatment arm assignment. Hazard ratios and corresponding 2-sided 95% confidence intervals will be estimated for TP53 status as well as treatment hazard ratios (with Arm 1 as the reference arm) within TP53 subgroups.
Prognostic and predictive associations of type of TP53 mutation status with OS
Will be assessed with proportional hazards modeling stratified for stratification factors at baseline and adjusted by randomized treatment arm assignment. Hazard ratios and corresponding 2-sided 95% confidence intervals will be estimated for TP53 status as well as treatment hazard ratios (with Arm 1 as the reference arm) within TP53 subgroups.
Incidence of adverse events (AEs) in treatment with bevacizumab when combined with carboplatin, paclitaxel, and pembrolizumab
The nature, frequency, and degree of toxicity will be tabulated at the system organ class and AE-specific term levels using Common Terminology Criteria for Adverse Events v 5.0. Each patient will be represented according to maximum grade observed for each term. Tabulations will show the number and percentage of patients by maximum grade, within the treatment group received, regardless of the randomized treatment assignment. No specific hypothesis test is pre-specified.
PFS
Will estimate the PFS treatment effect and the corresponding 95% confidence intervals by sex.
PFS
Will estimate the PFS treatment effect and the corresponding 95% confidence intervals by race.
PFS
Will estimate the PFS treatment effect and the corresponding 95% confidence intervals by ethnicity.
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