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

Official title

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

Overview

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.

Interventions

• 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.
• 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.

Primary outcome measures

• Clinical Benefit Rate [Time frame: Baseline, Up to 18 weeks]

Secondary outcome measures (9)

• Objective Response Rate (ORR) [Time frame: Up to 26 months]
• Progression-Free Survival (PFS) [Time frame: Up to 26 months]
• Overall Survival (OS) [Time frame: Up to 26 months]
• Duration of Response (DOR) [Time frame: Up to 26 months]
• Number of Participants Experiencing Treatment-Related Toxicity: Serious Adverse Events (SAEs) [Time frame: Up to 26 months]
• Number of Participants Experiencing Treatment-Related Toxicity: Adverse Events (AEs) [Time frame: Up to 26 months]
• Health-Related Quality of Life Scores: Patient-Reported Outcomes via EORTC QLQ-17 [Time frame: Up to 26 months]
• Health-Related Quality of Life Scores: Patient-Reported Social Isolation via Social Provisions Scale - 10 items (SPS-10) [Time frame: Up to 26 months]
• Health-Related Quality of Life Scores: Patient-Reported Social Needs via Health Leads 10-Item Screening Tool [Time frame: Up to 26 months]

Eligibility criteria

Inclusion criteria

• 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.
• 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 (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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• University of Miami — Miami

Identifiers

NCT: NCT07594015 · 20251180

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗