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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Clinical Benefit Rate [Срок оценки: Baseline, Up to 18 weeks]

Вторичные конечные точки (9)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Miami — Miami

Идентификаторы

NCT: NCT07594015 · 20251180

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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