A Phase I Study To Evaluate The Antitumor Activity And Safety Of DUKE-002-VRP(HUHER2-ECD+TM), An Alphaviral Vector Encoding The HER2 Extracellular Domain And Transmembrane Region, In Patient With Locally Advanced Or Metastatic Human Epidermal Growth Factor Receptor 2-Positive (HER2+) Cancers Including Breast Cancer

Inclusion Criteria:

- One of the following subgroups of patients with HER2 overexpression as follows:

(i) Histologically-confirmed breast cancer that is metastatic or locally
recurrent (7th Edition of the AJCC TNM System) and measurable and/or evaluable or
non-measurable by RECIST 1.1 criteria with HER2/neu overexpression by
immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having
received at least 1 prior FDA approved HER2 targeted therapy (e.g. trastuzumab or
lapatinib) (determined by their physician).*

*Prior therapy has at least one of the following stipulations:

1. Patients may have received neoadjuvant or adjuvant treatment with prior
trastuzumab or lapatinib treatment

2. Patients have received a trastuzumab-based therapy for locally advanced or
metastatic disease for a minimum of 9 weeks duration. Patients may have
received more than 1 trastuzumab-based combination therapy.

3. Patients have received a lapatinib-based therapy for locally advanced or
metastatic disease for a minimum of 9 weeks duration. Patients may have received
more than 1 lapatinib-based combination therapy.

(ii) Histologically-confirmed gastric or gastroesophageal adenocarcinoma that is
metastatic or locally recurrent (7th Edition of the AJCC TNM System) and
measurable or non-measurable by RECIST 1.1 criteria with HER2/neu overexpression
by immunohistochemistry (2+,3+) or FISH+ and progressive disease despite having
received at least 1 prior trastuzumab-containing regimen for a minimum of 9
weeks duration) (determined by their physician).

(iii) Other histologically confirmed metastatic (stage IV) or locally recurrent
(stage III) (7th Edition of the AJCC TNM System) malignancy with HER2/neu
overexpression by immunohistochemistry (2+,3+) or FISH+. Because there are no
other malignancies with FDA approved HER2 targeting therapies, no prior HER2
directed therapy will be required for this subgroup. However, patients will have
been required to have at least 1 line of therapy with a known survival benefit
for their malignancy.

- Adults at least 18 years of age at the time of signing the Informed Consent Form;

- Written informed consent and HIPAA authorization (applies to covered entities in the
USA only) obtained from the patient prior to performing any study-related procedures,
including screening visits;

- Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical
procedures to NCI CTCAE (version 4.03) Grade ≤ 1 (with the exception of grade 2
alopecia, grade 2 neuropathy and grade 2 fatigue);

- Karnofsky performance status greater than or equal to 80% or ECOG status of 0 or 1 ;

- Adequate hematologic function: (WBC = 2500 mm3, hemoglobin > 10 mg/dl, platelets >
100,000/mm3);

- Adequate renal and hepatic function (Cr < 2.0 mg/dl; bilirubin < 2 X ULN; AST < 2.5 x
ULN, ALT < 2.5 X ULN);

- Normal cardiac function defined as either a MUGA or ECHO with LVEF in normal
institutional range (MUGA 50%; ECHO 55%) and an EKG with no heart block;

- Female patients must be of non child-bearing potential or use effective
contraception, e.g., use of oral contraceptives with an additional barrier method
(since the study drug may impair the effectiveness of oral contraceptives), double
barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam),
Depo-Provera, partner vasectomy, total abstinence, and willing to continue the
effective contraception method for 30 days after the last dose of AVX901;

- Ability to return to Duke University Medical Center for adequate follow-up as
required by this protocol;

- Current therapy with endocrine agents (tamoxifen, raloxifene, torimifene and all
aromatase inhibitors) and/or bisphosphonates and/or RANK-ligand inhibitors is
permitted.

Exclusion Criteria:

- Except for patients on the concurrent trastuzumab cohort, patients may not receive
chemotherapy, monoclonal antibody, targeted therapy such as lapatinib, or radiation
therapy in the 3 weeks before the first injection, during the injection period or for
at least 2 weeks after the last injection. Patients may have received prior
radiation including for brain metastases.

- History of auto-immune disease such as, but not restricted to, inflammatory bowel
disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or
multiple sclerosis. Prior history of autoimmune thyroiditis or vitiligo is permitted.

- Serious intercurrent chronic or acute illness such as pulmonary (asthma or COPD) or
cardiac (NYHA class III or IV) or hepatic disease or other illness considered by the
P.I. to constitute an unwarranted high risk for investigational drug treatment.

- Medical or psychological impediment to probable compliance with the protocol.

- Concurrent or prior second malignancy (within the past 5 years) other than
non-melanoma skin cancer, controlled superficial bladder cancer or controlled
cervical cancer.

- Presence of active infection or systemic use of antimicrobials within 72 hours prior
to the first injection

- Patients on steroid therapy (or other immunosuppressives such as azathioprine or
cyclosporine A) are excluded on the basis of potential immune suppression. Patients
must have had 6 weeks of discontinuation of any steroid therapy prior to enrollment
(except steroids used as anti-emetics for systemic chemotherapy which are permitted).

- Presence of an active acute or chronic infection including HIV (as determined by
ELISA and confirmed by Western Blot) or viral hepatitis (as determined by HBsAg and
Hepatitis C serology). Patients with HIV are excluded based on immuno-suppression,
which may render them unable to respond to the vaccine; patients with chronic
hepatitis are excluded because of concern that hepatitis could be exacerbated by the
injections. .

- Pregnant or nursing women