Inclusion Criteria:

          -  Participants must have cytologically or histologically confirmed endometrial cancer
             that is recurrent or metastatic and/or resistant to standard therapies, or for which
             no standard therapy is available.

          -  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-certified laboratory.

          -  Participants must have measurable disease, defined as at least one lesion that can be
             accurately measured in at least one dimension (longest diameter to be recorded for
             non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional
             techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam.

          -  Age ≥ 18 years

          -  ECOG performance status of 0 or 1

          -  Participants must have normal organ and bone marrow function as defined below:

               -  Absolute neutrophil count ≥ 1,500/mcL

               -  Platelets ≥ 100,000/mcL

               -  Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)

               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional ULN, OR

                    -  5 × institutional ULN if liver metastases are present

               -  Creatinine ≤ 1.5 × institutional ULN, OR

               -  Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  The effects of the study agents on the developing human fetus are unknown. For this
             reason, women of child-bearing potential must agree to use a medically approved
             contraceptive method during the treatment period and for 3 months following the last
             dose of study agent. Contraceptive methods may include an intrauterine device (IUD) or
             barrier method. If condoms are used as a barrier method, a spermicidal agent should be
             added as a double barrier protection. Should a woman become pregnant or suspect she is
             pregnant while she is participating in this study, she should inform her treating
             physician immediately. A negative serum pregnancy test is required for study entry
             from women of childbearing potential.

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

          -  Ability to swallow and retain oral medication.

          -  Participants must have archival tissue available for analysis in the form of a
             formalin-fixed paraffin embedded (FFPE) block or unstained slides. Note: confirmation
             of availability of archival tissue is the only requirement for eligibility, archival
             tissue does not need to be received by the study team prior to enrollment

        Exclusion Criteria:

          -  Participants who have had chemotherapy, immune therapy, other investigational therapy,
             or major surgery within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to the
             first dose of study medication. Previous hormonal therapy, including prior letrozole,
             is allowed and there is no required washout period for hormonal therapy.

          -  Participants who have had tyrosine kinase inhibitor (TKI) therapy within 5 half-lives
             of study entry.

          -  Participants who have had radiation therapy within 2 weeks of the first dose of study
             medication.

          -  Participants who have received previous treatment with CDK4/6 inhibitors, including
             but not limited to previous abemaciclib therapy.

          -  Participants with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive neurologic
             dysfunction that would confound the evaluation of neurologic and other adverse events.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to the study agents that the participant will be administered.

          -  Participants who at the time of study enrollment are known to require concomitant
             therapy with moderate or strong CYP3A4 inducers, or strong inhibitors of CYP3A4. Due
             to potential drug interactions, concomitant use of these medications is not permitted
             for the duration of treatment on trial. Participants are eligible for study entry if
             an appropriate substitution is made prior to the first dose of study medication.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Participants with histories or evidence of cardiovascular risk including any of the
             following: acute coronary syndromes (i.e. myocardial infarction or angina), coronary
             angioplasty, or stenting within 6 months prior to study enrollment.

          -  Pregnant women are excluded from this study because the study agents are anti-cancer
             agents with the potential for teratogenic or abortifacient effects. Because there is
             an unknown but potential risk for adverse events in nursing infants secondary to
             treatment of the mother with the study agents, breastfeeding must be discontinued if
             the mother is treated on trial.

          -  Individuals with a history of a different malignancy are ineligible with the following
             exceptions: individuals who have been treated and are disease-free for a minimum of 5
             years prior to study enrollment, or individuals who are deemed by the treating
             investigator to be at low risk for disease recurrence. Additionally, individuals with
             the following cancers are eligible if diagnosed and treated within the past 5 years:
             basal or squamous cell carcinomas of the skin, and breast or cervical carcinomas in
             situ.

          -  Known HIV-positive participants are ineligible because of the increased risk of lethal
             infections when treated with marrow-suppressive therapy.

          -  Participants with a history of atrial fibrillation or atrial flutter.

          -  Participants with a history of uncontrolled hypertension despite optimal medical
             management, defined as systolic blood pressure > 150 mmHg or diastolic blood pressure
             > 90 mmHg