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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexFemale
• Healthy volunteersNo

You may be able to join if

• 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

You cannot join if

• 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 (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.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

lenvatinib mesylate. A synthetic, orally available inhibitor of vascular endothelial growth factor receptor 2 (VEGFR2, also known as KDR/FLK-1) tyrosine kinase with potential antineoplastic activity. Lenvatinib mesylate blocks VEGFR2 activation by VEGF, resulting in inhibition of the VEGF receptor signal transduction pathway, decreased vascular endothelial cell migration and proliferation, and vascular endothelial cell apoptosis. NCI Drug Dictionary

Treatments listed in the registry

• Pembrolizumab (Drug): Participants will receive 200mg of Pembrolizumab intravenously on Day 1 of every 21 day cycle, as per standard of care and as per institutional guidelines.
• Lenvatinib (Drug): Participants will self-administer Lenvatinib orally at a daily dose of 20mg or every 21 day cycle, as per standard of care and as per institutional guidelines.

Na · Single Group · masking: None

Main goals

• Clinical Benefit Rate (Baseline, Up to 18 weeks)

Other goals

• Objective Response Rate (ORR)
• Progression-Free Survival (PFS)
• Overall Survival (OS)
• Duration of Response (DOR)
• Number of Participants Experiencing Treatment-Related Toxicity: Serious Adverse Events (SAEs)
• Number of Participants Experiencing Treatment-Related Toxicity: Adverse Events (AEs)
• Health-Related Quality of Life Scores: Patient-Reported Outcomes via EORTC QLQ-17
• Health-Related Quality of Life Scores: Patient-Reported Social Isolation via Social Provisions Scale - 10 items (SPS-10)
• Health-Related Quality of Life Scores: Patient-Reported Social Needs via Health Leads 10-Item Screening Tool

Planned enrollment: 46 (estimated).

• University of Miami, Miami, Florida

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07594015
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C48636

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 23, 2026. Public record; not medical advice.