Eligibility Details:
Inclusion Criteria:
- Has Stage III, Stage IV, or recurrent, histologically-confirmed endometrial carcinoma
with disease that is either measurable or non-measurable but radiographically
apparent, per RECIST 1.1 as assessed by BICR (note: may have received prior
chemotherapy only if administered concurrently with radiation; may have received prior
radiation; and may have received prior hormonal therapy for treatment of endometrial
carcinoma, provided that it was discontinued ≥1 week prior to randomization)
- Has provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion that was not previously irradiated, for determination of mismatch
repair (MMR) status
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as
assessed within 7 days prior to the first dose of study intervention
- Is not pregnant or breastfeeding, and is either not a woman of childbearing potential
(WOCBP) or is a WOCBP who agrees to use contraception during the study and for ≥120
days after (pembrolizumab and lenvatinib) or ≥196 days after (chemotherapy) [if a
WOCBP, a pregnancy test will be required within 24 hours of first dose of study drug]
- Has adequately controlled blood pressure within 7 days prior to randomization
- Has adequate organ function based on assessment within 7 days prior to the first dose
of study intervention
Exclusion Criteria:
- Has carcinosarcoma (malignant mixed Műllerian tumor), endometrial leiomyosarcoma or
other high grade sarcomas, or endometrial stromal sarcomas
- Has a central nervous system (CNS) metastasis, unless local therapy (e.g., whole brain
radiation therapy, surgery, or radiosurgery) has been completed and have discontinued
use of corticosteroids for this indication for ≥4 weeks prior to starting study
medication (major surgery within 3 weeks of the first dose of study drug will be
exclusionary)
- Has a known additional malignancy (other than endometrial carcinoma) that is
progressing or has required active treatment in the last 3 years
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib
- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- Has radiographic evidence of major blood vessel invasion/infiltration
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to
randomization
- Has significant cardiovascular impairment within 12 months of the first dose of study
intervention such as history of congestive heart failure greater than New York Heart
Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular
accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability
- Has any infection requiring systemic treatment
- Has not recovered adequately from any toxicity and/or complications from major surgery
prior to randomization
- Has a known history of human immunodeficiency virus (HIV) infection (HIV test is
required at screening)
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg]
reactive) or known active Hepatitis C virus (Hepatitis B and C testing is required at
screening)
- Has a history of (non-infectious) pneumonitis that required treatment with steroids,
or has current pneumonitis
- Has a known history of active tuberculosis (tuberculosis test is required at
screening)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator
- Has a known psychiatric or substance abuse disorder that would interfere with
cooperation with the requirements of the study
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to randomization
- Has an active autoimmune disease (with the exception of psoriasis) that has required
systemic treatment in the past 2 years (i.e., with use of disease modifying agents,
corticosteroids or immunosuppressive drugs)
- Has received prior systemic chemotherapy in any setting for the treatment of
endometrial carcinoma (note: prior chemotherapy administered concurrently with
radiation is permitted)
- Has received prior radiotherapy within 4 weeks prior to randomization (participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis - a 2-week washout is
permitted for palliative radiation to non-CNS disease and vaginal brachytherapy)
- Has received prior hormonal therapy for the treatment of endometrial carcinoma within
1 week of randomization
- Has received prior therapy with any treatment targeting vascular endothelial growth
factor (VEGF)-directed angiogenesis, an anti-programmed cell death (PD)-1, anti-PD
ligand (L)1, or anti-PD L2 agent, or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137)
- Has received a live vaccine within 30 days prior to the first dose of study
intervention
- Has known intolerance to study intervention (or any of the excipients)
- Has had an allogenic tissue/solid organ transplant
- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to randomization
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-yes
