A Study of Avelumab With Axitinib Versus Sunitinib In Advanced Renal Cell Cancer (JAVELIN Renal 101)

Inclusion Criteria:

• Histologically or cytologically confirmed advanced or metastatic RCC with clear cellcomponent

• Availability of a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from ade novo tumor biopsy during screening (biopsied tumor lesion should not be a RECISTtarget lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can beprovided if the following criteria are met: 1) the biopsy or resection was performedwithin 1 year of randomization AND 2) the patient has not received any interveningsystemic anti-cancer treatment from the time the tissue was obtained andrandomization onto the current study. If an FFPE tissue block cannot be provided asper documented regulations then, 15 unstained slides (10 minimum) will be acceptable

• Availability of an archival FFPE tumor tissue from primary tumor resection specimen (if not provided per above). If an FFPE tissue block cannot be provided as perdocumented regulations 15 unstained slides (10 minimum) will be acceptable

• At least one measurable lesion as defined by RECIST version 1.1 that has not beenpreviously irradiated

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Adequate bone marrow function, renal and liver functions

Exclusion Criteria:

• Prior systemic therapy directed at advanced or metastatic RCC

• Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse hasoccurred during or within 12 months after the last dose of treatment.

• Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, antiCD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cellco stimulation or immune checkpoint pathways

• Prior therapy with axitinib and/or sunitinib as well as any prior therapies withother VEGF pathway inhibitors

• Newly diagnosed or active brain metastasis

• Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), anyhistory of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partiallycontrolled asthma Global Initiative for Asthma 2011)

• Any of the following in the previous 12 months: myocardial infarction,severe/unstable angina, coronary/peripheral artery bypass graft, symptomaticcongestive heart failure, LVEF less than LLN, clinically significant pericardialeffusion, cerebrovascular accident, transient ischemic attack

• Any of the following in the previous 6 months: deep vein thrombosis or symptomaticpulmonary embolism

• Vaccination within 4 weeks of the first dose of avelumab and while on trial isprohibited except for administration of inactivated vaccines (for example,inactivated influenza vaccines)