Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

PRIMARY OBJECTIVES:

I. Determine the safety of DC205-NY-ESO-1 vaccine (DEC-205/NY-ESO-1 fusion protein CDX-1401)
with and without sirolimus. Toxicity as defined by the National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

SECONDARY OBJECTIVES:

I. Assess the NY-ESO-1 specific cellular and humoral immunity:

- Peripheral blood NY-ESO-1 specific cluster of differentiation (CD)8+ and CD4+ T-cells.

- Peripheral blood NY-ESO-1 specific antibodies.

- Peripheral blood frequency of CD4+CD25+forkhead box P3 (FOXP3)+ regulatory T-cells.

TERTIARY OBJECTIVES:

I. Explore time to disease progression.

OUTLINE:

Patients undergo standard collection of peripheral white blood cells via leukapheresis over
90-240 minutes for vaccine preparation. Patients are assigned sequentially to Cohorts 1a-1d.

COHORT 1a: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 intranodally on days 1,
29, 57, and 113.

COHORT 1b: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and
sirolimus orally (PO) on days 1-14, 29-42, and 57-70.

COHORT 1c: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and
sirolimus PO or percutaneous endoscopic gastrostomy (PEG) tube on days 15-28, 43-56, and
71-84.

COHORT 1d: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in Cohort 1a and
sirolimus PO or PEG on days 1-84.

COHORT 2: Patients receive DEC-205/NY-ESO-1 fusion protein CDX-1401 as in the Cohort (1a-1d)
that is determined to be safe and produces optimal immunological effects and sirolimus PO on
days 1-14 as in Cohort 1b dose.

After completion of study treatment, patients are followed up at 6 weeks, 6 months and 12
months.

Inclusion Criteria:

- Patients with any solid tumors at high risk of recurrence or with minimal residual
disease; there may or may not be measurable or symptomatic disease (i.e., patients
with bladder, brain, breast, esophageal, gastrointestinal, hepatocellular, kidney,
lungs, melanoma, ovarian, prostate, sarcomas, and uterine)

- Cancer types:

- Prostate cancer: patients with metastatic, castrate refractory prostate cancer;
the use of luteinizing hormone-releasing hormone (LHRH) agonist is allowed

- Kidney cancer: patients with metastatic kidney cancer; prior therapies with
cytokines, vascular endothelial growth factor (VEGF) and mechanistic target of
rapamycin (serine/threonine kinase) (mTOR) inhibitors are allowed

- Bladder cancer: patients with metastatic urothelial carcinoma; prior
cisplatin-based therapies are allowed

- Ovarian cancer: eligible patients may have asymptomatic residual measurable
disease on physical examination and/or computed tomography (CT) scan, and/or may
have an elevated cancer antigen (CA)-125; or may be in complete clinical
remission after treatment for primary or recurrent disease

- Brain tumors: histologic proof of one of the following: glioblastoma multiforme,
anaplastic astrocytoma, anaplastic oligodendroglioma or anaplastic mixed glioma
or anaplastic oligoastrocytoma; patients who have had recent cranial surgery are
eligible for inclusion, but the vaccine may not be administered prior to
postoperative day 14

- Uterine cancer: patients with advanced (stages II-IV) or recurrent disease who
have completed standard therapy, currently no evidence of disease (NED) or with
minimal residual disease; patients with stage I uterine serous carcinomas or
sarcomas are also eligible after completion of standard therapy

- Breast cancer: patients can enter study after completion of all chemotherapy
(including trastuzumab), radiation, and breast/axillary surgery; patients may
participate while on endocrine therapy; stages I-III patients with the following
characteristics:

- Estrogen-receptor (ER) negative with positive lymph nodes; ER negative with
negative nodes if tumor > 2 cm; ER positive with positive lymph nodes; and
ER positive with negative lymph nodes and tumor > 5 cm

- Sarcomas: patients with sarcomas of any site, who have completed standard
therapy, and are in remission, or have minimal disease burden

- Lungs: resected patients with hilar or ipsilateral mediastinal nodal disease
(i.e., a subset of patients with stage II and IIIA disease); and patients with
residual disease on imaging after definitive radiation or chemoradiation therapy

- Esophageal: resected patients with any nodal (i.e., thoracic or abdominal)
disease; and patients with residual disease on imaging after definitive
chemoradiation therapy

- Melanoma: stage IIB, stage IIC, and stage III who have completed planned
definitive therapy for their disease including radiotherapy and/or interferon;
patients declining interferon or with contra-indications to interferon will also
be eligible provided they meet requisite criteria for this study (i.e.,
non-measurable disease); stage IV melanoma of M1a sub-type only, who are not
candidates for additional therapy of curative potential (i.e., small volume
disease; may be measurable or evaluable); and stage IV melanoma, NED, status
post (s/p) complete resection of known sites of disease (i.e., non-measurable
disease)

- Hepatocellular carcinoma (HCC): patients who have been treated with surgical
resection for HCC; and following chemoembolization as adjuvant therapy for HCC

- Gastrointestinal: patients who have completed standard therapies for gastric and
colorectal cancers, and deemed to be at high-risk of relapse

- Any human leukocyte antigen (HLA) type; historic HLA typing is permitted

- Tumor expression of NY-ESO-1 or LAGE-1 by immunohistochemistry (IHC) and/or reverse
transcription polymerase chain reaction (RTPCR)

- Life expectancy > 6 months

- Absolute neutrophil count (ANC) >= 1,000/uL

- Platelets (PLT) >= 75,000/uL

- Hemoglobin (Hgb) >= 8 g/dL

- Total bilirubin =< 1.5 x upper limit of normal (ULN)

- Serum aspartate aminotransferase (serum glutamic oxaloacetic transaminase
[SGOT]/aspartate aminotransferase [AST]) or serum alanine aminotransferase (serum
glutamate pyruvate transaminase [SGPT]/alanine aminotransferase [ALT]) =< 3 x ULN

- Serum creatinine =< 2 x ULN

- Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 x ULN; patients
receiving anticoagulation therapy, PT/INR =< 3

- Pulmonary function tests: forced expiratory volume in one second (FEV1) > 50% and
diffusion capacity of the lungs for carbon monoxide (DLCO) > 50%

- Pulse oximetry: oxygen (O2) saturation >= 90% on room air

- Electrocardiogram, showing no clinical significant or acute abnormality

- Have been informed of other treatment options

- Patient or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

- Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

- Patients of child-bearing potential must agree to use acceptable contraceptive
methods (e.g., double barrier) during treatment

Exclusion Criteria:

- Metastatic disease to the central nervous system for which other therapeutic options,
including radiotherapy, may be available

- Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
disorders)

- History of severe autoimmune disorders requiring use of steroids or other
immunosuppressives

- Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal
anti-inflammatory drugs, aspirin > 325 mg; specific cyclooxygenase (COX)-2 inhibitors
are permitted

- Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first
dosing of study agent (6 weeks for nitrosoureas); concomitant hormonal therapies for
breast and prostate cancers are allowed

- Clinically significant heart disease (New York Heart Association [NYHA] class III or
IV) within 6 months

- Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study

- Lack of availability of a patient for immunological and clinical follow-up assessment

- Known pulmonary hypertension

- Known hypersensitivity to sirolimus

- Evidence of current drug or alcohol abuse or psychiatric impairment, which in the
investigator's opinion will prevent completion of the protocol therapy or follow-up

- Pregnant or nursing female patients

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the patient an unsuitable
candidate to receive study drug; (i.e., any significant medical illness or abnormal
laboratory finding that would, in the investigator's judgment, increase the subject's
risk by participating in this study)

- Received an investigational agent within 30 days prior to enrollment

- Known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)