Endometrial Cancer Clinical Trials

• Participants must have histologically confirmed either i) endometrioid endometrial cancer or ii) endometrial carcinosarcoma with endometrioid epithelial component.

• Participants must have ER-positive disease, defined as ≥ 1 percent of tumor cell nuclei being immunoreactive by immunohistochemistry (IHC). If multiple analyses have been performed, judgment should be based on the most recent biopsy or pathology specimen analyzed in a CLIA (Clinical Laboratory Improvement Amendments)-certified laboratory.

• Tumor must be TP53 wild-type as determined by immunohistochemistry (IHC) or via CLIA-certified targeted Next-Generation Sequencing (NGS); IHC assessment of p53 status is included in the NCCN guidelines of uterine neoplasms for the molecular analysis of endometrial carcinoma.

• Participants must have mismatch repair proficient (MMRP) endometrial cancer as determined by immunohistochemistry (IHC) or polymerase chain reaction (PCR) or any CLIA-certified next generation sequencing assay.

• No known tumor mutational burden ≥ 10 mutations/megabase (Mb).

• No known RB1 mutations or two-copy RB1 deletion.

• Participants must have just completed a minimum of 4 cycles and a maximum of 10 cycles of a combination of carboplatin and taxane or a combination of taxane and anti-PD-(L)1 inhibitor therapy (e.g., pembrolizumab, or dostarlimab, or durvalumab).

• Participants must have had measurable stage III, measurable stage IVA, stage IVB (with or without measurable disease) or recurrent (with or without measurable disease) endometrial cancer.

• Participants are permitted to have received:

‣ a. Prior adjuvant chemotherapy (e.g., paclitaxel/carboplatin alone or as a component of concurrent chemotherapy and radiation therapy \[with or without cisplatin\])

⁃ b. Prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/paraaortic radiation therapy, intravaginal brachytherapy, and/or palliative radiation therapy. All radiation therapy must have been completed at least 4 weeks prior to registration.

⁃ c. Prior hormonal therapy for treatment of endometrial cancer.

• Must be able to initiate study drug between 3 to 8 weeks (or 21 to 56 days) after completion of their final dose of chemotherapy and anti-PD-(L)1 blockade (if they were receiving anti-PD-(L)1 blockade).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix A)

• Age ≥ 18 years

• Participants must have normal organ and bone marrow function within 2 weeks before starting protocol therapy as defined below:

‣ System Laboratory Value

⁃ Hematologic

• ANC ≥1.5 × 109 /L

∙ Platelets ≥100 × 109 /L

∙ Hemoglobin ≥8 g/dL Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.

⁃ Hepatic

• Total bilirubin ≤1.5 × ULN Patients with Gilbert's syndrome with a total bilirubin ≤2.0 times ULN and direct bilirubin within normal limits are permitted.

∙ ALT and AST ≤3 × ULN

∙ Creatinine ≤ 1.5 × institutional ULN, OR

∙ Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above 1.5 x institutional ULN.

∙ Abbreviations: ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase; ULN = upper limit of normal.

• Ability to understand and the willingness to sign a written informed consent document.

• Ability to swallow and retain oral medication.

• Participants must be willing to release archival tissue if available. Please see section 9.1.2 and the laboratory manual for tissue requirements.