- Histologically or cytologically confirmed advanced or metastatic RCC with clear cell
- Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a
RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue
block (cut slides not acceptable) from a primary or metastatic tumor resection or
biopsy can be provided if the following criteria are met: 1) the biopsy or resection
was performed within 1 year of randomization AND 2) the patient has not received any
intervening systemic anti-cancer treatment from the time the tissue was obtained and
randomization onto the current study.
- 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, 15 unstained
slides (10 minimum) will be acceptable
- At least one measureable lesion as defined by RECIST version 1.1 that has not been
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate bone marrow function, renal and liver functions
- Prior systemic therapy directed at advanced or metastatic RCC.
- Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has
occurred during or within 12 months after the last dose of treatment
- Prior immunotherapy with IL-2, IFN-?, or anti PD 1, anti PD L1, anti PD L2, anti
CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody
(including ipilimumab), or any other antibody or drug specifically targeting T cell
co stimulation or immune checkpoint pathways
- Prior therapy with axitinib and/or sunitinib as well as any prior therapies with
other vascular endothelial growth factor (VEGF) pathway inhibitors.
- Known severe hypersensitivity reactions to monoclonal antibodies (Grade ?3), any
history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially
controlled asthma Global Initiative for Asthma 2011).
- Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart
failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or
symptomatic pulmonary embolism.
- Vaccination within 4 weeks of the first dose of avelumab and while on trial is
prohibited except for administration of inactivated vaccines (for example,
inactivated influenza vaccines).