Pembrolizumab and Lenvatinib for the Treatment of Mismatch Repair Proficient Recurrent Endometrial Cancer

Inclusion Criteria

• Histologically confirmed recurrent endometrial carcinoma, including serous, endometrioid, carcinosarcoma, clear cell subtypes, with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
• MMR-proficient status confirmed by immunohistochemistry (IHC) or molecular testing
• Patients must have progressed on or after first-line maintenance immunotherapy that was started while on carboplatin-based doublet chemotherapy and continued following chemotherapy until completion (prior chemotherapy for this disease administered before the most recent line is permitted)
• Prior radiation is permitted but not required
• Patient must have completed next-generation sequencing on either primary or recurrent tumor
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 3
• Age ≥ 18 years
• Female participants must be of non-childbearing potential or for females of child bearing potential (FOCPs), must agree to use contraception. FOCBPs must not be pregnant or breastfeeding
• At least one measurable lesion according to RECIST 1.1
• Hemoglobin ≥ 8 g/dL (blood transfusions are permitted)
• Absolute neutrophil count ≥ 1000
• Platelet count ≥ 100 x 10^9/L
• Glomerular filtration rate (GFR) ≥ 30 mL/min
• Bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Written informed consent obtained from the patient
• At least 3 weeks must have elapsed from any prior therapy

Exclusion Criteria

• Uterine sarcoma
• Active central nervous system metastases or leptomeningeal disease
• History of severe allergic reactions to pembrolizumab, lenvatinib, or any components of the formulations
• Active autoimmune disease requiring chronic systemic steroids for > 3 months in the last 6 months prior to enrollment
• Pregnancy or breastfeeding at the time of enrollment
• Previous treatment with lenvatinib or other VEGFR inhibitors
• Concurrent treatment with other investigational drugs or anti-cancer therapies except for adjuvant hormonal therapy for breast cancer
• Uncontrolled concurrent illness, such as active infections that could interfere with study participation
• Blood pressure > 160 systolic or > 110 diastolic averaged over last 3 documented measurements
• History of significant cardiovascular events within 12 months prior to enrollment, including myocardial infarction, unstable angina, or congestive heart failure (New York Heart Association [NYHA] Class III or IV)
• History of organ transplant or immune suppressive therapy that would interfere with the efficacy or safety of the investigational drugs
• Other malignancies within the past 2 years except for non-melanoma skin cancer
• Patients that have received more than one prior line of immunotherapy