The researchers are doing this study to evaluate the use of circulating tumor DNA (ctDNA) testing in making treatment decisions for advanced/recurrent endometrial cancer that has a change (mutation) in the mismatch repair deficient (MMR-D) gene or microsatellite instability high (MSI-H) gene. The researchers will see how doctors and their patients use the results of ctDNA testing after 1 year of standard chemotherapy and immune checkpoint inhibitor (ICI) treatment to decide whether to continue maintenance ICI treatment past 1 year. The researchers will also look at the health outcomes of people in this study (for example, whether they are cancer free at the end of their participation in the study).

Inclusion Criteria:

• Patients must have pathologically confirmed endometrial cancer

• Patients with advanced endometrial cancer

• Stage III with residual disease

• Stage IV

• Recurrent endometrial cancer after adjuvant therapy only

• Patients can have primary or planned interval surgery

• MMR-D on immunohistochemistry OR MSI-H using any commercially available test

• Patients with treated brain metastases are eligible if follow up brain imaging after CNS directed therapy shows no evidence of progression.

• Eligible for standard of care chemotherapy with immune checkpoint inhibitor per treating investigator with no clinical contraindications

• For the up to 10 patients who are allowed to enroll after C1D1 of standard of care treatments, they need to be on treatment with no clinical evidence of disease progression.

  • 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.

  • Patients may have received prior hormonal therapy for treatment of endometrial cancer.

  • Patients may not have received prior therapy with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 therapeutic antibody or other similar agents.

    • Except for the up to 10 patients who are allowed to enroll after C1D1 of standard of care treatments (chemotherapy and/or immune checkpoint inhibitors) per protocol.

• Age ≥ 18

• Not Pregnant and Not Nursing

Endometrial Cancer

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.