Pembrolizumab and Lenvatinib in Mismatch Repair Proficient Recurrent Endometrial Cancer After Failure of First-Line Therapy With Platinum-based Doublet and Immunotherapy

Phase 2 Open-Label Trial Investigating the Efficacy and Safety of Pembrolizumab and Lenvatinib in Mismatch Repair Proficient Recurrent Endometrial Cancer After Failure of First-Line Therapy With Platinum-based Doublet and Immunotherapy

The purpose of this study is to determine the efficacy and safety of Pembrolizumab in combination with Lenvatinib in recurrent, mismatch repair-proficient endometrial cancer after failure of first-line therapy with a platinum-based doublet chemotherapy and immunotherapy.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Endometrial Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Lenvatinib

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Navya Nair, MD, MPH; Phone Number: 305-243-2233; Email: navya.nair@miami.edu
• Study Contact Backup: Name: Abdulrahman Sinno, MD; Phone Number: 305-243-2233; Email: axs3193@miami.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33146
      • Recruiting
      • University of Miami
      • Contact: Navya Nair, MD, MPH; Phone Number: 305-243-2233; Email: navya.nair@miami.edu
      • Contact: Abdulrahman Sinno, MD; Phone Number: 305-243-2233; Email: axs3193@miami.edu
      • Principal Investigator: Navya Nair, MD, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed recurrent endometrial carcinoma, including serous, endometrioid, carcinosarcoma, clear cell subtypes, with measurable disease per RECIST 1.1 criteria.
2. Mismatch repair (MMR) proficient status confirmed by IHC (Immunohistochemistry) or molecular testing.
3. Patients must have failed first-line therapy with platinum based doublet with prior immunotherapy.
4. Patient must have completed next-generation sequencing on either primary or recurrent tumor.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3.
6. Age ≥ 18 years.
7. Female participants must be of non-childbearing potential or for females of child bearing potential (FOCBPs), must agree to use contraception as described in Section 5.6. FOCBPs must not be pregnant or breastfeeding.
8. At least one measurable lesion according to RECIST 1.1.

9. 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)
10. Written informed consent obtained from the patient.
11. At least 3 weeks must have elapsed from any prior therapy

Exclusion Criteria:

1. Uterine sarcoma
2. Active central nervous system metastases or leptomeningeal disease.
3. History of severe allergic reactions to pembrolizumab, lenvatinib, or any components of the formulations.
4. Active autoimmune disease requiring chronic systemic steroids for > 3 months in the last 6 months prior to enrollment.
5. Pregnancy or breastfeeding at the time of enrollment.
6. Previous treatment with lenvatinib or other VEGFR inhibitors.
7. Concurrent treatment with other investigational drugs or anti-cancer therapies except for adjuvant hormonal therapy for breast cancer.
8. Uncontrolled concurrent illness, such as active infections that could interfere with study participation.
9. Blood pressure >160 systolic or >110 diastolic averaged over last 3 documented measurements.
10. 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).
11. History of organ transplant or immune suppressive therapy that would interfere with the efficacy or safety of the investigational drugs.
12. Other malignancies within the past 2 years except for non-melanoma skin cancer.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pembrolizumab in combination with Lenvatinib; Participants will receive Pembrolizumab in combination with Lenvatinib after failure of first-line therapy with a platinum-based doublet chemotherapy in combination with immunotherapy. Participants may receive treatment for a total of up to approximately 24 months, or until participants have progression of disease or experience a Grade 4 or higher severe adverse event (SAE). Total participation duration is approximately 26 months.

Drug: Pembrolizumab; 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.; Other Names: Keytruda; Drug: Lenvatinib; 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.; Other Names: Lenvima

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate	Clinical benefit rate (CBR) is defined as the proportion of participants achieving complete response (CR), partial response (PR) or sustained stable disease (SD), as the best response as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.	Baseline, Up to 18 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the proportion of participants achieving complete response (CR) or partial response (PR) as the best response assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.	Up to 26 months
Progression-Free Survival (PFS)	Progression-Free Survival (PFS) is the elapsed time in months from date of treatment initiation until progression or death from any cause. Patients who are alive and without documented disease progression will be censored at the date of their last disease assessment.	Up to 26 months
Overall Survival (OS)	Overall Survival (OS) is the elapsed time in months from date of treatment initiation until death from any cause. Alive patients will be censored at the last date known to be alive.	Up to 26 months
Duration of Response (DOR)	Duration of Response (DOR) is the elapsed time in months from date of first documentation of complete response (CR) or partial response (PR) until first documentation of progression or death from any cause for responders. Patients who are alive and without documented disease progression will be censored at the date of their last disease assessment.	Up to 26 months
Number of Participants Experiencing Treatment-Related Toxicity: Serious Adverse Events (SAEs)	The safety and tolerability of combination Pembrolizumab and Lenvatinib therapy will be reported as the number of participants experiencing treatment-related serious adverse events (SAEs). SAEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.	Up to 26 months
Number of Participants Experiencing Treatment-Related Toxicity: Adverse Events (AEs)	The safety and tolerability of combination Pembrolizumab and Lenvatinib therapy will be reported as the number of participants experiencing treatment-related adverse events (AEs). AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.	Up to 26 months
Health-Related Quality of Life Scores: Patient-Reported Outcomes via EORTC QLQ-17	Participant quality of life will be assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 17 (EORTC QLQ-17), a validated 17-item questionnaire measuring global health status and functional domains relevant to cancer patients. Items are scored using standardized Likert scales and converted to 0-100 domain scores according to EORTC scoring guidelines. Higher scores indicate better functioning and overall quality of life.	Up to 26 months
Health-Related Quality of Life Scores: Patient-Reported Social Isolation via Social Provisions Scale - 10 items (SPS-10)	Social isolation will be measured using the 10-item short form of the Social Provisions Scale, a validated instrument assessing perceived social support and relational connectedness. Each item is rated on a 4-point Likert scale (1 = Strongly Disagree, 2 = Disagree, 3= Agree, 4 = Strongly Agree), yielding a total score ranging from 10 to 40, with higher scores indicating greater perceived social support (lower social isolation).	Up to 26 months
Health-Related Quality of Life Scores: Patient-Reported Social Needs via Health Leads 10-Item Screening Tool	Unmet social needs will be assessed using the 10-item Health Leads Social Needs Screening Tool, a validated questionnaire identifying needs such as food insecurity, housing instability, transportation barriers, and utility challenges. Each item is coded as 1 (unmet need present) or 0 (no unmet need). Total scores represent the count of unmet social needs (range 0-10), with higher scores indicating greater social needs burden.	Up to 26 months

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Navya Nair, MD, MPH, University of Miami

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 18, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Endometrial Neoplasms; pembrolizumab; lenvatinib
• Other Study ID Numbers: 20251180

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No