Pembrolizumab Plus Lenvatinib for First-line Advanced/Metastatic Non-clear Cell Renal Cell Carcinoma (1L nccRCC) (MK-3475-B61)

Inclusion Criteria: 1. Must have a histologically confirmed diagnosis of nccRCC. 2. Has locally advanced/metastatic disease (ie, Stage IV per the American Joint Committee on Cancer). 3. Has received no prior systemic therapy for advanced nccRCC. Note: Prior neoadjuvant/adjuvant therapy for nccRCC is acceptable if completed \>12 months prior to allocation. 4. Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of study medication, or refrain from heterosexual intercourse during this period. 5. Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period and for at least 120 days post pembrolizumab, or 30 days post lenvatinib, whichever occurs last. 6. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 7. Has submitted an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue. 8. Has Karnofsky Performance Status (KPS) ≥70% as assessed within 10 days prior to the start of study intervention. 9. Has adequately controlled blood pressure with or without antihypertensive medications 10. Have adequate organ function. Exclusion Criteria: 1. Has collecting duct histology. 2. A WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention. 3. Has a left ventricular ejection fraction below the institutional (or local laboratory) normal range. 4. Has radiographic encasement or invasion of a major blood vessel, or of intratumoral cavitation. 5. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention. 6. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib. 7. Has active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug. 8. Has had major surgery within 3 weeks prior to first dose of study intervention. 9. Has received prior therapy with an anti-programmed cell-death 1 (PD-1), anti-programmed cell-death ligand 1 (PD-L1), or anti-programmed cell-death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137). 10. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to allocation. 11. Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease. 12. Has received a live or attenuated vaccine within 30 days before the first dose of study intervention. 13. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. 14. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. 15. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. 16. Has known active CNS metastases and/or carcinomatous meningitis. 17. Has severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients. 18. Has an active autoimmune disease that has required systemic treatment in past 2 years 19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 20. Has an active infection requiring systemic therapy. 21. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority. 22. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus. 23. Has a known history of active tuberculosis (TB; Bacillus tuberculosis). 24. Has had an allogenic tissue/solid organ transplant.