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 cell
component

- Availability of a 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
(not cut slides) 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. If an FFPE tissue block cannot be provided as per 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 providedas per
documented regulations 15 unstained slides (10 minimum) will be acceptable

- At least one measureable lesion as defined by RECIST version 1.1 that has not been
previously 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 has
occurred 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, 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
VEGF pathway inhibitors

- Newly dignosed or active brain metastasis

- 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 12 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
LVEF less than LLN, clinically significant pericardial effusion, cerebrovascular
accident, transient ischemic attack

- Any of the following in the previous 6 months: 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)