Purpose

This is a multicenter, randomized, open-label, Phase 3 study to compare the efficacy and safety of lenvatinib in combination with everolimus (Arm A) or pembrolizumab (Arm B) versus sunitinib (Arm C) as first-line treatment in participants with advanced renal cell carcinoma.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histological or cytological confirmation of renal cell carcinoma (RCC) with a clear-cell component
  • At least 1 measurable target lesion according to Response Evaluation in Solid Tumors (RECIST) 1.1
  • Karnofsky Performance Status (KPS) of ≥70
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1 (C1/D1)
  • Adequate organ function per blood work

Exclusion Criteria

  • Participants who have received any systemic anticancer therapy for RCC, including anti-vascular endothelial growth factor (VEGF) therapy, or any systemic investigational anticancer agent
  • Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy (WBRT), surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
  • Active malignancy (except for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix or bladder) within the past 24 months. Subjects with history of localized & low risk prostate cancer are allowed in the study if they were treated with curative intent and there is no prostate specific antigen (PSA) recurrence within the past 5 years
  • Prior radiation therapy within 21 days prior to start of study treatment with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks prior to study treatment start
  • Received a live vaccine within 30 days of planned start of study treatment
  • Participants with urine protein ≥1 gram/24 hour
  • Fasting total cholesterol >300 milligram per deciliter (mg/dL) (or ˃7.75 millimole per liter (mmol/L)) and/or fasting triglycerides level ˃2.5 x upper limit of normal (ULN). Note: these subjects can be included after initiation or adjustment of lipid-lowering medication
  • Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: these participants can be included after initiation or adjustment of glucose-lowering medication
  • Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)
  • Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy
  • Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
  • Significant cardiovascular impairment within 12 months of the first dose of study drug: history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident, or cardiac arrhythmia associated with hemodynamic instability. The following is also excluded: left ventricular ejection fraction below the institutional normal range as determined by multiple-gated acquisition scan or echocardiogram
  • Active infection (any infection requiring systemic treatment)
  • Participants known to be positive for Human Immunodeficiency Virus (HIV).
  • Known active Hepatitis B (eg, Hepatitis B surface antigen (HBsAg) reactive) or Hepatitis C (eg, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is detected)
  • Known history of, or any evidence of, interstitial lung disease
  • Has a history of (non-infectious) pneumonitis that required steroids, or current pneumonitis
  • Participants with a diagnosis of immunodeficiency or who are receiving chronic systemic steroid therapy (doses exceeding 10 mg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. Physiologic doses of corticosteroids (up to 10 mg/day of prednisone or equivalent) may be used during the study
  • Active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Known intolerance to any of the study drugs (or any of the excipients)

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Lenvatinib 18 mg plus everolimus 5 mg
Lenvatinib 18 milligrams (mg) administered orally, once daily, plus everolimus 5 mg administered orally, once daily
  • Drug: lenvatinib
  • Drug: everolimus
Experimental
Lenvatinib 20 mg plus pembrolizumab 200 mg
Lenvatinib 20 mg administered orally, once daily, plus pembrolizumab 200 mg administered intravenously (IV), every 3 weeks
  • Drug: lenvatinib
  • Drug: pembrolizumab
Active Comparator
Sunitinib 50 mg
Sunitinib 50 mg administered orally, once daily, on a schedule of 4 weeks on treatment followed by 2 weeks off treatment
  • Drug: Sunitinib

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10461

More Details

NCT ID
NCT02811861
Status
Recruiting
Sponsor
Eisai Inc.

Study Contact

Eisai Medical Information
1-888-274-2378
esi_medinfo@eisai.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.