A Phase III Randomized, Open-label Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy as a First-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-426)

• Histologically confirmed diagnosis of RCC with clear cell component with or without sarcomatoid features

• Stage IV disease (locally advanced/metastatic)

• Measurable disease

• No prior systemic therapy for advanced RCC

• Archival or new tissue sample required

• KPS >70%

• If receiving bone resorptive therapy must have been on stable dose at least 4 weeks

• Adequate organ function

• No prior treatment with immunotherapy (eg. PD-1, GITR, IDO inhibitors)

• No VEGF or mTOR targeting agents within 12 months

• No active autoimmune disease

• No other malignancy within last 3 years

• No active CNS disease

• No known HIV, HBV, HCV

• No severe cardiovascular disease

Primary: PFS, OS; Secondary: ORR, DCR, safety

Pembrolizumab 200mg IV q3 weeks and Axitinib 5mg PO bid vs. sunitinib 50mg PO qday 4 wks on 2 wks off