This is a Phase 2 trial Safety Lead-in trial conducted in 3 cohorts of patients.

A safety lead-in study of the impact of adding the Repurposed Drugs a third agent will be conducted prior to opening enrollment into the compassionate use study. All patients enrolled in the safety lead-in study may continue long-term treatment under this protocol without interruption of dosing.

Inclusion Criteria:

1. Female, 18 years and older at the time of informed consent, who has a histologically confirmed diagnosis of endometrial carcinoma, endometroid histology, that is not MSI-H or dMMR ).
2. Documented evidence of advanced (Stage III or IV), or recurrent EC.
3. Must have a recurrence or progressed on a platinum containing chemotherapy regimen and are not candidates for curative surgery or radiation
4. Has historical or fresh tumor biopsy specimen for confirmation of mismatch repair (MMR) status as not MSI-H or dMMR.
5. Has measurable or evaluable disease according to Response Evaluation Criteria In Solid Tumors (RECIST v1.1).
6. Is a candidate for initiation of treatment with the combined regimen of Keytruda plus Lenvima (Len+Pem) OR IS CURRENTLY RECEIVING a tolerated regimen of Len+Pem at the doses specified as the Len+Pem Regimen (per Labeling July 2021)
7. Life expectancy of 12 weeks or more.
8. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days of starting study treatment.
9. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle 1 Day 1.
10. Adequate renal function defined as creatinine less than or equal to 1.5 × ULN (upper limit of normal) or calculated creatinine clearance greater than or equal to 40 mL/min per the Cockcroft and Gault formula with creatinine levels greater than 1.5 × ULN.

Additional detail upon request.

Exclusion Criteria:

1. Brain metastasis: Previously treated CNS disease needs to be asymptomatic and does not require steroids. Brain metastases must be asymptomatic, fully treated and stable and not requiring steroids within 4 weeks prior to study treatment initiation.
2. Has carcinosarcoma (malignant mixed mullerian tumor), serous carcinoma, endometrial leiomyosarcoma and endometrial stromal sarcomas.
3. Has failed treatment of lenvatinib + pembrolizumab in prior lines of therapy.
4. Except for the allowance of ongoing use of Len+Pem, the protocol excludes patients having received any other prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is shorter) or any investigational agent within 30 days prior to the first dose of study drugs. All acute toxicities related to prior treatments must be resolved to Grade less than or equal to 1.
5. Participants must have recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
6. Participants having greater than 1+ proteinuria on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Participants with urine protein greater than or equal to 1 g/24-hour will be ineligible.
7. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of the study drugs
8. Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
9. Has radiographic evidence of major blood vessel invasion/infiltration.
10. Has clinically significant tumor bleeding within 2 weeks prior to the first dose of study treatment.

Additional detail upon request.