Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma

This is a trial of AGS-003, which is being studied as a possible treatment for Advanced Renal Cell Carcinoma. The purpose of this study is to determine whether there is an overall survival (OS) benefit between subjects treated with AGS-003 in combination with standard treatment versus subjects treated with standard treatment alone.

This study will investigate the combination of an autologous ribonucleic acid (RNA) electroporated dendritic cell (DC) based immunotherapy, AGS-003, plus standard treatment (initiating with sunitinib). The primary objective in this study is to determine the median OS achieved by this combination compared to the OS resulting from use of active control (standard treatment), in a population of adults with advanced renal cell carcinoma (RCC), with nephrectomy indicated, and with remaining metastatic disease.

Eligibility Criteria:
Key Inclusion Criteria for Tumor Collection:

1. Diagnosis or clinical signs of advanced RCC
2. Scheduled for cytoreductive or partial nephrectomy

Key Exclusion Criteria for Tumor Collection:

1. Known inability to undergo sunitinib treatment as currently labeled, due to pre-existing medical conditions
2. Requirement for systemic chronic immunosuppressive drugs or corticosteroids
3. Evidence of brain metastases prior to nephrectomy

Key Inclusion Criteria for Treatment Study:

1. Advanced disease, histologically assessed as RCC, with predominantly clear cell histology
2. Metastatic disease (measurable or non-measurable) that can be monitored throughout the course of the study participation per RECIST 1.1
3. Subjects who are candidates for standard first-line therapy initiating with sunitinib
4. Time from diagnosis to treatment \< 1 year
5. Karnofsky performance status (KPS) ≥ 70%
6. Life expectancy of 6 months or greater
7. Resolution of all acute toxic effects of prior radiotherapy or surgical procedures to Grade ≤ 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
8. Adequate hematologic, renal, hepatic, and coagulation function
9. Negative serum pregnancy test for female subjects with reproductive potential, and agreement of all male and female subjects of reproductive potential to use a reliable form of contraception during the study and for 12 weeks after the last dose of study drug
10. Normal ECG or clinically non-significant finding(s) at Screening
11. Able to abstain from taking prohibited drugs, either prescription or non-prescription, during the treatment phase of the study
12. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Key Exclusion Criteria for Treatment Study:

1. Prior systemic therapy (including adjuvant or neoadjuvant) of any kind for RCC, including immunotherapy, chemotherapy, hormonal, or investigational therapy
2. Prior history of malignancy within the preceding 3 years, except for adequately treated in situ carcinomas or non-melanoma skin cancer, adequately treated early stage breast cancer, superficial bladder cancer, and non-metastatic prostate cancer with a normal PSA
3. History of or known brain metastases, spinal cord compression, or carcinomatous meningitis, or evidence of brain or leptomeningeal disease
4. Patients with 4 or more of the following risk factors:

   1. Hgb \< LLN
   2. Corrected calcium \> 10.0 mg/dL
   3. KPS \< 80%
   4. Neutrophils \> ULN
   5. Platelets \> ULN
5. Planned or elective surgical treatment post-nephrectomy for the direct management of RCC, within 28 days before Visit 1 (Week 0)
6. NCI CTCAE Grade 3 hemorrhage \< 28 days before Visit 1 (Day 0)
7. Clinically significant cardiovascular conditions within 3 months prior to Randomization
8. Significant gastrointestinal abnormalities
9. Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
10. Active autoimmune disease or condition requiring chronic immunosuppressive therapy
11. Clinically significant infections, including human immunodeficiency virus, syphilis, and active hepatitis B or C
12. Current treatment with an investigational therapy on another clinical trial
13. Pregnancy or breastfeeding
14. Any serious medical condition or illness considered by the investigator to constitute an unwarranted high risk for investigational treatment