Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma

Inclusion Criteria:

   1. Histological or cytological confirmation of RCC with a clear-cell component (original
   tissue diagnosis of RCC is acceptable).

   2. Documented evidence of advanced RCC.

   3. At least 1 measurable target lesion according to RECIST 1.1 meeting the following
   criteria:

      - Lymph node (LN) lesion that measures at least 1 dimension as greater than or
      equal to (>=) 1.5 cm in the short axis

      - Lymph node (LN) lesion that measures at least 1 dimension as greater than or
      equal to (>=) 1.5 centimeter (cm) in the short axis

      - Non-nodal lesion that measures greater than or equal to (>=) 1.0 cm in the
      longest diameter

      - The lesion is suitable for repeat measurement using computerized
      tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external
      beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence
      of disease progression based on RECIST 1.1 to be deemed a target lesion.

3.Karnofsky Performance Status (KPS) of >=70 4.Adequately controlled blood pressure (BP)
with or without antihypertensive medications, defined as BP less than or equal (<=) 150/90
millimeter of mercury (mmHg) at Screening and no change in antihypertensive medications
within 1 week prior to Cycle 1/Day 1 (C1/D1) 5.Adequate renal function defined as
creatinine <=1.5*upper limit of normal (ULN); or for participants with creatinine greater
than (>) 1.5*ULN, the calculated creatinine clearance >=30 milliliters per minute (mL/min)
(per the Cockcroft-Gault formula) is acceptable.

6.Adequate bone marrow function defined by:

   - Absolute neutrophil count (ANC) >=1500/cubic millimeter (mm^3)

   - Platelets >=100,000/mm^3

   - Hemoglobin >=9 grams per deciliter (g/dL) NOTE: Criteria must be met without
   erythropoietin dependency and without packed red blood cell (pRBC) transfusion within
   the previous 2 weeks.

   7.Adequate blood coagulation function defined by International Normalized ratio (INR)
   <=1.5 unless participant is receiving anticoagulant therapy, as long as INR is within
   therapeutic range of intended use of anticoagulants.

   8.Adequate liver function defined by:

   - Total bilirubin <=1.5*ULN except for unconjugated hyperbilirubinemia of Gilbert's
   syndrome.

   - Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate
   aminotransferase (AST) <=3*ULN (in the case of liver metastases <=5*ULN), unless there
   are bone metastases. Participants with ALP values >3*ULN and known to have bone
   metastases can be included.

   9.Provide written informed consent. 10.Willing and able to comply with all aspects of
   the protocol.

Exclusion Criteria:

   1. Participants who have received any systemic anticancer therapy for RCC, including
   anti-vascular endothelial growth factor (VEGF) therapy, or any systemic
   investigational anticancer agent. Prior adjuvant treatment with an investigational
   anticancer agent is not allowed unless the investigator can provide evidence of
   participant's randomization to placebo arm.

   2. Participants with central nervous system (CNS) metastases are not eligible, unless
   they have completed local therapy (example, 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
   (example, radiologic) or symptoms of CNS metastases must be stable for at least 4
   weeks before starting study treatment

   3. 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. Participants 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

   4. 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

   5. Participants who are using other investigational agents or who had received
   investigational drugs <=4 weeks prior to study treatment start.

   6. Received a live vaccine within 30 days of planned start of study treatment (Cycle
   1/Day 1). Examples of live vaccines include, but are not limited to, measles, mumps,
   rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
   Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
   are generally killed virus vaccines and are allowed; however, intranasal influenza
   vaccines (example, FluMist®) are live attenuated vaccines and are not allowed.

   7. Participants with proteinuria >1+ on urine dipstick testing will undergo 24-h urine
   collection for quantitative assessment of proteinuria. Participants with urine protein
   >=1 g/24 h will be ineligible

   8. 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 participants can be included after initiation or adjustment of
   lipid-lowering medication

   9. 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

10. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms)

11. Participants who have not recovered adequately from any toxicity and/or complications
   from major surgery prior to starting therapy.

12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition
   that might affect the absorption of lenvatinib, everolimus, and/or sunitinib.

13. Bleeding or thrombotic disorders or participants 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

14. Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first
   dose of study drug

15. 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 (LVEF) below the institutional normal range as
   determined by multiple-gated acquisition MUGA scan or echocardiogram

16. Active infection (any infection requiring systemic treatment)

17. Participants known to be positive for Human Immunodeficiency Virus (HIV).

18. Known active Hepatitis B (example, Hepatitis B surface antigen (HBsAg) reactive) or
   Hepatitis C (example, hepatitis C virus ribonucleic acid (HCV RNA) [qualitative] is
   detected)

19. Known history of, or any evidence of, interstitial lung disease

20. Has a history of (non-infectious) pneumonitis that required steroids, or current
   pneumonitis

21. 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

22. Active autoimmune disease (with the exception of psoriasis) that has required systemic
   treatment in the past 2 years (that is, with use of disease modifying agents,
   corticosteroids or immunosuppressive drugs). Replacement therapy (example, thyroxine,
   insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
   insufficiency) is not considered a form of systemic treatment.

23. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
   positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin
   [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or
   hCG]). A separate baseline assessment is required if a negative screening pregnancy
   test was obtained more than 72 hours before the first dose of study drug.

24. Females of childbearing potential who:

      - Do not agree to use a highly effective method of contraception for the entire
      study period and for 120 days after study discontinuation, that is:

      - total abstinence (if it is their preferred and usual lifestyle)

      - an intrauterine device (IUD) or hormone-releasing system (IUS)

      - a contraceptive implant

      - an oral contraceptive (with additional barrier method) OR

      - Do not have a vasectomized partner with confirmed azoospermia. For sites outside
      of the EU, it is permissible that if a highly effective method of contraception
      is not appropriate or acceptable to the participant, then the participant must
      agree to use a medically acceptable method of contraception, that is, double
      barrier methods of contraception such as condom plus diaphragm or cervical/vault
      cap with spermicide.

25. Males who have not had a successful vasectomy (confirmed azoospermia) and do not agree
   to use condom + spermicide OR have a female partner who does not meet the criteria
   above (that is, is of childbearing potential and not practicing highly effective
   contraception throughout the study period), starting with the first dose of study
   therapy through 120 days after the last dose of study therapy, unless sexually
   abstinent. Note: Abstinence is acceptable if this is the usual lifestyle and preferred
   contraception for the participant.

26. Known intolerance to any of the study drugs (or any of the excipients)

27. Participant has had an allogenic tissue/solid organ transplant.