A Study of Avelumab in Combination With Axitinib In Non-Small Cell Lung Cancer (NSCLC) or Urothelial Cancer (Javelin Medley VEGF)

• Non-Small Cell Lung Cancer
• Urothelial Cancer

• Drug: Avelumab (MSB0010718C)
  IV treatment: Avelumab administered at 800 mg IV every two weeks
  Other Name: Bavencio
• Drug: Axitinib (AG-013736)
  Oral treatment: Axitinib given 5 mg PO BID
  Other Name: Inlyta

Inclusion Criteria:

• Non-small cell lung cancer (NSCLC) Cohort: Histologically or cytologically confirmed diagnosis of NSCLC that is locally advanced or metastatic; No activating EGFR mutations, ALK or ROS1 translocations/rearrangements where testing is standard of care; received at least 1 prior platinum?based chemotherapy regimen for locally advanced or metastatic NSCLC; No more than 2 prior lines of systemic therapy for locally advanced or metastatic disease (If disease progression occurred during or within 6 months after neoadjuvant/adjuvant chemotherapy or radiotherapy?chemotherapy, the regimen is counted as 1 prior treatment regimen towards the allowed limit of prior treatment regimens); Checkpoint inhibitor naïve.
• Urothelial Cancer (UC) Cohort: Histologically or cytologically confirmed diagnosis of transitional cell carcinoma (TCC) of the urothelium (if mixed, more than 50% TCC component) including bladder, urethra, ureters, or renal pelvis that is locally advanced or metastatic; No prior systemic treatment for locally advanced or metastatic disease; Prior neoadjuvant or adjuvant therapy is permitted if disease progression occurred >12 months after the completion of therapy; Checkpoint inhibitor naïve; Ineligible for receiving cisplatin?containing front?line chemotherapy based at least one of the following criteria: ECOG performance status (PS) 2; Renal dysfunction (defined as creatinine?clearance <60 ml/min); Grade 2 peripheral neuropathy; Grade 2 hearing loss (hearing loss measured by audiometry of 25 decibels at two contiguous frequencies).
• At least 1 measurable lesion by RECIST v1.1 not previously irradiated.
• Availability of an archival FFPE tumor tissue block from primary diagnosis specimen or metastatic specimen or 15 unstained slides (10 minimum). If an archived sample is not available, a fresh tumor biopsy must be performed.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. For UC patients, ECOG performance 2 is permitted (cisplatin ineligibility criterion)

Exclusion Criteria:

• Prior immunotherapy with an anti?PD?1, anti?PD?L1, anti?PD?L2, anti?CD137, anti?OX?40, anti?GITR, anti?LAG?3, anti?TIM?3 or anti?CTLA?4 antibody (including ipilimumab).
• Newly diagnosed brain metastases or known symptomatic brain metastases requiring steroids.
• Radiologically documented evidence of major blood vessel invasion or encasement by cancer or intratumor cavitation, regardless of tumor histology.
• Active autoimmune disease (that might deteriorate when receiving an immunostimulatory agent).
• Current use of immunosuppressive medication (except for those listed in protocol).
• Known prior severe hypersensitivity to the investigational products /monoclonal antibodies.
• Known history of immune?mediated colitis, inflammatory bowel disease, immune?mediated pneumonitis, pulmonary fibrosis.
• NCI CTCAE Grade 3 hemorrhage within 28 days prior to study enrollment.