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Keynote 775: A multi-center, open-label, randomized phase 3 trial to compare the efficacy and safety of lenvatinib in combination with pembrolizumab versus treatment of physician's choice in participants with advanced endometrial cancer

Description

This is a study of pembrolizumab (MK-3475, KEYTRUDA®) in combination with lenvatinib (E7080) versus treatment of physician's choice (doxorubicin or paclitaxel) for the treatment of advanced endometrial cancer. Participants will be randomly assigned to receive either pembrolizumab and lenvatinib or treatment of physician's choice.

Status

Accepting new patients

Primary Study Objective(s)

The primary study hypothesis is that pembrolizumab, in combination with lenvatinib, prolongs progression-free survival (PFS) and overall survival (OS) when compared to a treatment of physician's choice.

Core eligibility

Note: This is only a partial list of eligibility criteria.

Including patients who:

  • Have a histologically confirmed diagnosis of endometrial carcinoma (EC) and documented evidence of advanced, recurrent or metastatic EC
  • Have radiographic evidence of disease progression after one prior systemic, platinum-based chemotherapy regimen for recurrent, metastatic or primary unresectable disease
  • Have a historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status
  • Have at least one measurable target lesion, according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within three days of the start of the study 
  • Are not pregnant, breastfeeding, and agree to use a highly effective method of contraception during the treatment period and for at least 120 days after the last dose of study treatment

Excluding patients who:

  • Have carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas
  • Have unstable central nervous system (CNS) metastases
  • Have an active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within 24 months of the start of the study 
  • Have a gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
  • Have radiographic evidence of major blood vessel invasion/infiltration
  • Have clinically significant hemoptysis or tumor bleeding within two weeks prior to the first dose of study treatment
  • Have a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment
  • Have an active infection requiring systemic treatment
  • Have not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy
  • Are positive for Human Immunodeficiency Virus (HIV)
  • Have active Hepatitis B or C
  • Have a history of (non-infectious) pneumonitis that required treatment with steroids, or have current pneumonitis
  • Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
  • Have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within seven days prior to study start; Have an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past two years
  • Are pregnant or breastfeeding
  • Have received >1 prior systemic anticancer regimen (other than adjuvant or neoadjuvant) for advanced, recurrent or metastatic EC
  • Have received prior anticancer treatment within 28 days of the start of the study. All acute toxicities related to prior treatments must be resolved to grade ≤1, except for alopecia and grade ≤2 peripheral neuropathy
  • Have received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
  • Have received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who have discontinued that treatment due to a grade 3 or higher immune-related adverse event
  • Have received prior radiation therapy within 21 days of the start of the study with the exception of palliative radiotherapy to bone lesions, which is allowed if completed two weeks before the start of the study
  • Have received a live vaccine within 30 days of the start of the study 
  • Have a known intolerance to study treatment (or any of the excipients).
  • Are currently participating in, or have participated in, a study of an investigational agent or have used an investigational device within four weeks of the start of the study 
  • Have a urine protein ≥1 gram (g)/24 hour
  • Have prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)
  • Have a left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)