Autologous Dendritic Cells in Treating Patients With Metastatic Kidney Cancer

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of dendritic cell (DC)-AdGM carbonic anhydrase IX
(CAIX) administered by intradermal injections at study doses and schedule.

SECONDARY OBJECTIVES:

I. To evaluate clinical antitumor effects following study treatment according to Response
Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.1. Parameters include
objective response (complete response [CR], partial response [PR]), duration of response in
patients with objective response, and time to disease progression.

II. To evaluate immune responses to DC-AdGMCAIX vaccination by enzyme-linked immunospot
(ELISpot) for numeric determination of CAIX specific T cells in blood.

III. To evaluate immune responses to DC-AdGMCAIX vaccination by cytokine profiling of T cell
culture supernatants for characterization of the immune response in subjects with
demonstrated immune activation may be performed.

IV. To evaluate immune responses to DC-AdGMCAIX vaccination by anti-sargramostim (GM-CSF)
antibody response.

V. To evaluate tumor biopsies for immune cell infiltrates.

OUTLINE: This is a dose-escalation study.

Patients receive AdGMCAIX-transduced autologous dendritic cells intradermally (ID) on days 1,
15, and 29.

After completion of study treatment, patients are followed up every 2-3 months for at least 6
months.

Inclusion Criteria:

- Histologically or cytologically confirmed clear cell renal cell carcinoma (ccRCC);
pathology report from the original diagnosis of renal cell carcinoma is acceptable;
the component of conventional clear cell type > 50% is mandatory

- Evidence of metastatic disease with measurable lesion(s) as defined by RECIST
guideline version 1.1 to permit tumor response evaluation; subjects with unresected
primary tumors may be enrolled as long as evidence of measurable metastatic disease is
also present

- Signed informed consent

- Eastern Cooperative Oncology Group (ECOG) =< 1

- Expected life expectancy >= 6 months

- Serum creatinine < 2 mg/dL

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 X upper
limit of normal (ULN)

- Total bilirubin < 2 X ULN (except for subjects with documented Gilbert's syndrome who
can have total bilirubin < 3.0 mg/dl)

- Hemoglobin >= 10 g/dL

- Absolute neutrophil count >= 1.5 X 10^9 cells/L

- Platelets >= 100 X 10^9/L

- Having recovered from prior surgery, radiation, chemotherapy (cytotoxic and
noncytotoxic) to toxicity grade =< 1 or returned to baseline; previous treatment with
immunotherapies, cytotoxic drugs, or other targeted agents is permitted; if cytotoxic
chemotherapy was previously received, the last dose must be >= 1 month before
leukapheresis; for other agents, the last dose must be >= 14 days before leukapheresis

- Negative serum pregnancy test within 7 days prior to enrollment in female subjects
with reproductive potential

Exclusion Criteria:

- Rapidly progressing cancer likely to require palliative systemic intervention within 8
weeks after study entry

- Presence of untreated/active central nervous system (CNS) metastases

- For subjects with metastatic RCC who have had no prior systemic treatment for RCC and
are considered a poor risk according to Motzer criteria, defined by having >= 3 of the
following 5 risk factors for short survival: Karnofsky performance score < 80%,
lactate dehydrogenase (LDH) > 1.5 X of ULN, hemoglobin < lower limit of normal (LLN),
corrected serum calcium > 10 mg/dL (2.5mM), a time from initial diagnosis of RCC to
initiation of systemic therapy of < 1 year

- Non-clear cell or predominantly (> 50%) sarcomatoid histology

- Concurrent major medical conditions, such as uncontrolled hypertension, diabetes
mellitus, ischemic heart disease, chronic obstructive pulmonary disease, autoimmune
disease, adrenal insufficiency, or prior allogeneic organ transplant requiring chronic
immunosuppressive therapy, including systemic glucocorticoid treatment or replacement
therapy

- Active or chronic systemic infection, including viral hepatitis, human
immunodeficiency virus (HIV), mycobacteria, tuberculosis (TB), or other opportunistic
infections

- Having received systemic immune suppressive therapy within 30 days prior to
leukapheresis

- Having received an investigational agent within 30 days prior to the first dose of
study treatment

- Female subjects who are lactating, pregnant or both male and female subjects with
reproductive potential who refuse to practice medically accepted methods for
contraception over the period from study consent to 90 days following the last dose of
study treatment

- Other malignancy within 3 years, except for adequately treated non-melanoma skin
cancer, non-invasive cancers such as cervical or breast carcinoma in situ, or
superficial bladder cancer without local recurrence

- Social or psychological conditions that the investigator judges may compromise study
compliance