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

NCT07594015 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20251180
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Objective Response Rate (ORR)

  Up to 26 months

• Progression-Free Survival (PFS)

  Up to 26 months

• Overall Survival (OS)

  Up to 26 months

• Duration of Response (DOR)

  Up to 26 months

• Number of Participants Experiencing Treatment-Related Toxicity: Serious Adverse Events (SAEs)

  Up to 26 months

Study Arms (1)

Pembrolizumab in combination with Lenvatinib

EXPERIMENTAL

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; Drug: Lenvatinib

Interventions

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.

Also known as: Keytruda

Pembrolizumab in combination with Lenvatinib

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.

Also known as: Lenvima

Pembrolizumab in combination with Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify 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 IHC (Immunohistochemistry) or molecular testing.
• Patients must have failed first-line therapy with platinum based doublet with prior immunotherapy.
• 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 Section 5.6. 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.

You may not qualify 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.

Sponsors & Collaborators

• University of Miami: lead

Study Sites (1)

University of Miami

Miami, Florida, 33146, United States

RECRUITING

MeSH Terms

Conditions

Endometrial Neoplasms

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Study Officials

• Navya Nair, MD, MPH

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Navya Nair, MD, MPH

CONTACT

305-243-2233; navya.nair@miami.edu

Abdulrahman Sinno, MD

CONTACT

305-243-2233; axs3193@miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Clinical

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 18, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: May 18, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)