A Rollover Protocol for Subjects Previously Treated With AGS-003

• Tumor response [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
  Clinical antitumor activity of AGS-003 will be assessed as an objective tumor response by Response Evaluation Criteria in Solid Tumors (RECIST).
  
  

• Clinical benefit (stable disease or response) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
  Clinical benefit measured as Stable Disease (SD), Partial Response (PR), and Complete Response (CR) rate to the treatment regimen. Tumor response is verified using standard definitions of RECIST
  
  
• Immune function [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Analyses of immune function will be performed. This will include, but not limited to, assessment of T cell and antigen presenting cell populations, including effector memory, cytotoxic lymphocytes (CTLs), and regulatory T cells. Blood and plasma specimens for these analyses will be collected at specified time points and is optional for subjects continuing with booster treatments.
  
  
• Progression Free Survival (PFS) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
  Evaluate PFS from the date of registration until PFS is reached per RECIST
  
  
• Overall Survival (OS) [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: No ]
  Evaluate OS from date of registration unitl date of death.
  
  
• Treatment-emergent Adverse Events [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Monitor incidence of treatment-emergent Adverse Events.
  
  
• Monitor clinical chemistry, hematology, and urinalysis for treatment-emergent changes from baseline [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Clinical laboratory values will be monitored for changes from baseline.
  
  
• Physical Examinations [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Monitor changes from baseline in physical examinations
  
  
• Vital Signs [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Monitor changes from baseline in vital signs
  
  
• Monitor signs and symptoms indicating treatment-emergent autoimmunity [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Autoimmunity evaluations will be measured by clinical signs and symptoms (e.g., rash, cytopenias, and arthralgias) and by laboratory assessments. These assessments will be monitored as long as the subject is receiving AGS-003.
  
  
• Monitor for lymph node adenopathy [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  The draining lymph nodes (axillary and inguinal) will be evaluated for changes from baseline in size, tenderness, or inflammation. These assessments will be monitored as long as the subject is receiving AGS-003.
  
  
• Injection Site Reaction [ Time Frame: From date of registration until either disease progression, meeting a discontinuation criterion, or death; assessed up to 36 months. ] [ Designated as safety issue: Yes ]
  Monitor changes from baseline in injection site reactions.
  
  

AGS-003-005 is a rollover, open label, Phase II clinical study testing the biologic activity and safety of AGS-003 in subjects who have experienced either partial responses or prolonged stable disease and continue to benefit from ongoing treatment with AGS-003 in protocols AGS-003-004 or AGS-003-006.

Rollover subjects from AGS-003-004 will continue with AGS-003 monotherapy booster dosing until disease progression or until a discontinuation criterion is reached.

Subjects that progress on AGS-003 monotherapy (from the AGS-003-004 protocol) may start sunitinib treatment and re-initiate AGS-003 therapy beginning with the induction phase dosing schedule.

Rollover subjects from AGS-003-006 will continue sunitinib dosing in combination with booster dosing of AGS-003 until disease progression or until a discontinuation criterion is reached.

If a subject has disease progression due to a new tumor lesion, upon consultation between the investigator, Argos representatives and the Argos medical monitor, the subject may be considered for re-manufacture of study product (from the new metastatic lesion) and dosing with this new product in combination with sunitinib beginning with the induction phase dosing schedule.

For those subjects initiating treatment with the induction phase as described above, restaging imaging occurs at screening (baseline), prior to the fifth dose in the induction phase (as applicable) and every 12 weeks during the booster phase (at the start of the sunitinib holiday, 2 weeks prior to the next AGS-003 dose).

For subjects on combination therapy, if dosing with sunitinib is stopped due to sunitinib-related issues, treatment with AGS-003 may continue.

Close-out visits will occur upon disease progression (other than circumstances discussed above which are eligible for re-induction) or upon decision to terminate the study by the sponsor.

Quarterly follow-up for survival for each subject will occur by telephone interview for 1 year following the last AGS-003 administration or study termination.