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.
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 ).
Documented evidence of advanced (Stage III or IV), or recurrent EC.
Must have a recurrence or progressed on a platinum containing chemotherapy regimen and are not candidates for curative surgery or radiation
Has historical or fresh tumor biopsy specimen for confirmation of mismatch repair (MMR) status as not MSI-H or dMMR.
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.
Has carcinosarcoma (malignant mixed mullerian tumor), serous carcinoma, endometrial leiomyosarcoma and endometrial stromal sarcomas.
Has failed treatment of lenvatinib + pembrolizumab in prior lines of therapy.
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.