Pembrolizumab and Lenvatinib in Mismatch Repair Proficient Recurrent Endometrial Cancer After Progression on or Following First-Line Immunotherapy Maintenance

Prior treatment

• Active autoimmune disease requiring chronic systemic steroids for \> 3 months in the last 6 months prior to 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.
• History of significant cardiovascular events within 12 months prior to enrollment, including myocardial infarction, unstable angina, or congestive heart failure (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.
• Patients that have received more than one prior line of immunotherapy.

Other illness

• Active central nervous system metastases or leptomeningeal disease.
• History of severe allergic reactions to pembrolizumab, lenvatinib, or any components of the formulations.
• Other malignancies within the past 2 years except for non-melanoma skin cancer.

Other

• Uterine sarcoma
• Pregnancy or breastfeeding at the time of enrollment.
• Blood pressure \>160 systolic or \>110 diastolic averaged over last 3 documented measurements.

• Histologically confirmed recurrent endometrial carcinoma, including serous, endometrioid, carcinosarcoma, clear cell subtypes, with measurable disease per RECIST 1.1 criteria.
• Mismatch repair (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 (FOCBPs), must agree to use contraception as described in protocol. FOCBPs must not be pregnant or breastfeeding.
• At least one measurable lesion according to RECIST 1.1.
• Adequate organ function, including:
  • Hemoglobin ≥ 8 g/dL (blood transfusions are permitted)
  • Absolute neutrophil count ≥ 1000
  • Platelet count ≥ 100 x 10⁹/L
  • Glomerular filtration rate (GFR) ≥ 30 mL/min
  • Bilirubin ≤ 1.5 x ULN (upper limit of normal)
• Written informed consent obtained from the patient.
• At least 3 weeks must have elapsed from any prior therapy