A Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received Any Chemotherapy for Advanced Disease

Inclusion Criteria

• Males or females age ≥18 years at the time of informed consent form (ICF)
• Participants with histologically confirmed non clear cell renal cell carcinoma (nccRCC) who have not received any chemotherapy for advanced disease. Participants must have one of the following subtypes of nccRCC: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
• Radiologically measurable disease meeting the following criteria:
• At least 1 lesion of ≥10 millimeters (mm) in the longest diameter for a nonlymph node or ≥15 mm in the short axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computerized tomography (CT) or magnetic resonance imaging (MRI);
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ≥20%) to be deemed a target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Blood pressure (BP) ≤140/90 millimeters of mercury (mmHg) at Screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1.
• Adequate renal function as evidenced by calculated creatinine clearance ≥30 milliliters (mL)/minute according to the Cockcroft and Gault formula
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥1.5 × 10^9/liter (L);
• Hemoglobin ≥10.0 grams per deciliter (g/dL) (can be corrected by growth factor or transfusion prior to first dose of study drug);
• Platelet count ≥100 × 10^9/L
• Adequate liver function:
• Bilirubin ≤1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome;
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if participant has liver metastases). If ALP is >3 × ULN (in the absence of liver metastases) or >5 × ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.
• Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria

• Predominant clear cell renal cell carcinoma (RCC)
• Prior anticancer chemotherapy or targeted therapy for advanced nccRCC
• Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor
• Known intolerance to lenvatinib, everolimus (or other rapamycin derivatives), or any of the excipients
• Major surgery performed within 3 weeks prior to the first dose of study drugs or scheduled for major surgery during the study
• Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib or everolimus
• Participants having >1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 grams (g)/24 hours will be ineligible.
• Fasting total cholesterol ˃300 milligrams (mg)/dL (or ˃7.75 millimoles [mmol]/L) or fasting triglycerides level ˃2.5 × ULN. Note: these participants can be included after initiation or adjustment of lipid-lowering medication.
• Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: In case this threshold is exceeded, these participants can only be included after initiation or adjustment of glucose-lowering medication.
• Known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.
• Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarctio