Examining Bioactivity of PVSRIPO in Triple Negative Breast Cancer

The study drug PVSRIPO is the live attenuated, oral (Sabin) serotype 1 poliovirus vaccine
containing a heterologous internal ribosomal entry site (IRES) derived from the human
rhinovirus type 2 (HRV2). The purpose of this pilot study is to examine PVSRIPO bioactivity
in tumor tissue after intratumoral administration of PVSRIPO in women with triple negative
breast cancer (TNBC). The hypothesis is that administration of PVSRIPO in the tumor causes
inflammation, which stimulates innate and adaptive immune activation in TNBC. Enrollment
target will include six women with TNBC. Women with stage II-IV ER/PR/HER2 negative (triple
negative) breast cancer with at least 1 cm of residual tumor after chemotherapy and scheduled
for standard of care surgery will be eligible.

The objective of the study is to investigate PVSRIPO-mediated inflammation and immunity in
women TNBC. The primary exploratory objective is to describe the change in the amount of
tumor infiltrating immune cells in tumor tissue pre- and post-injection of PVSRIPO by H&E
(Haemotoxylin and Eosin).

Other exploratory objectives are: 1.) to examine tumor tissue pre- and post-injection of
PVSRIPO for inflammatory and immune signature using arrays, CD155 expression by
immunohistochemistry (IHC), immune cell infiltrate by IHC and tumor infiltrating immune cells
using flow cytometry (post-injection only); and 2) To examine blood for inflammatory and
immune signature using arrays, immune cell composition (antigen presenting cells, B cells and
T cells), T cell activation by flow cytometry and B cell activation by ELISA and peptide
arrays. Blood will be collected on day -7 (before polio vaccine booster), day 0 (before
PVSRIPO injection), day 2 (after PVSRIPO), day 14 (after PVSRIPO before surgery), and in
follow-up at months 1 and 6 post-PVSRIPO.

This pilot study will include women with stage II-IV ER/PR/HER2 negative (triple negative)
breast cancer scheduled to undergo surgical resection.

Inclusion Criteria:

- Age ≥ 18 years

- Confirmation of TNBC defined as follows: triple-negative receptor status is defined as
estrogen receptor expression ≤ 10%, progesterone receptor expression ≤ 10%, and
HER2/Neu expression by IHC 0 or 1+, or 2+ with fluorescence in situ hybridization
confirming no amplification of HER2 on a pretreatment tumor sample and prior to
initiation of chemotherapy if chemotherapy is planned.

- Stage II-III TNBC with ≥ 1 cm of residual tumor based on MRI, mammogram, ultrasound,
or breast clinical exam as SOC after completion of neoadjuvant chemotherapy, OR Stage
IV TNBC with ≥ 1 cm locally recurrent disease (i.e. chest wall recurrence only)

- ECOG ≤ 1

- Hemoglobin ≥ 9.0 g/dl, ANC ≥ 1,500 cells/µl, platelets ≥ 125,000 cells/µl

- Women must have had last dose of chemotherapy at least 3 weeks prior to treatment with
PVSRIPO

- Women must have at least 2 weeks minimum (ideal 3-4 weeks) of a wash-out period after
any steroid administration (IV, PO, or intraocular)

- Serum creatinine ≤ 1.5 mg/dl, serum SGOT and bilirubin ≤ 1.5 times ULN (upper limit of
normal)

- Women must provide written informed consent prior to enrollment on study

- Women of childbearing potential will have a negative serum pregnancy test at screening

- Women of childbearing potential must be willing to avoid pregnancy for the course of
the study through 120 days after PVSRIPO injection

- Surgical resection of the tumor is planned and patient is willing to undergo surgical
resection of the cancer

Exclusion Criteria:

- Stage I TNBC

- Breast cancer with skin necrosis

- Concurrent immune therapy, chemotherapy, or steroid therapy

- Is currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks prior to polio vaccine booster

- Has a known diagnosis of immunodeficiency

- Has a known additional malignancy that is progressing or requires active treatment

- Has known active central nervous system metastases and/or carcinomatous meningitis

- Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease or a syndrome that
requires systemic steroids or immunosuppressive agents

- Has an active infection requiring systemic therapy

- Has known psychiatric or substance abuse disorders that would interfere with the
requirements of the trial

- Is pregnant, breastfeeding, or expecting to conceive children within the projected
duration of the trial, starting with the screening visit through 120 days after trial
treatment

- Has received prior therapy with an anti-PD-1, anti-PDL-1, anti-PDL-2, anti-CD137, or
anti-CTLA-4 (or any other antibody or drug specifically targeting T cell
co-stimulation or checkpoint pathways)

- Has a known history of Human Immunodeficiency Virus (HIV)

- Has known active Hepatitis B or Hepatitis C

- Active liver disease with elevated transaminases > 2x ULN

- Has received a live vaccine within 30 days prior to PVSRIPO treatment

- Inactivated vaccines are acceptable and are not an exclusion criterion