Combination Study of SV-BR-1-GM in Combination With Pembrolizumab

This is an open-label, single arm study of the SV-BR-1-GM regimen in patients with metastatic
or locally recurrent breast cancer who have failed at least one line of therapy. Patients may
enter this study directly or may roll-over from Study WRI-GEV-007, "A Phase I/IIa Study of
SV-BR-1-GM in Metastatic or Locally Recurrent Breast Cancer Patients". Those patients who
have exhibited disease progression on Study WRI-GEV-007, and patients entering directly into
this study, will receive the SV-BR-1-GM regimen with combination immunotherapy. The
SV-BR-1-GM regimen consists of:

1. Pre- SV-BR-1-GM cyclophosphamide 2-3 days prior to SV-BR-1-GM inoculation

2. SV-BR-1-GM inoculation

3. Interferon-alpha-2b - at the inoculation sites 2±1 days post-SV-BR-1-GM

4. Interferon-alpha-2b - at the inoculation sites 4±1 days post-SV-BR-1-GM

5. Combination therapy with pembrolizumab (KEYTRUDA®, anti-PD-1).

The SV-BR-1-GM regimen in combination with pembrolizumab will be administered every 3 weeks
+/- 5 days. After the first year of therapy, consideration should be given to decreasing the
frequency of therapy (monthly, every 6 weeks, etc.) by the PI in consultation with the
Sponsor. Note that hormonal therapy (e.g., aromatase inhibitors) is permitted if ongoing, but
may be added while the patient is on this study only with the Sponsor's approval.

Patients will be screened to assure they fulfill the enrollment criteria. Screening must be
performed within 30 days of initiating therapy, and imaging studies must be performed within
2 weeks of initiating therapy unless approved by the Sponsor. Patients rolling over from
Study WRI-GEV-007 who have been treated within 6 weeks of the first dose can enter directly
into treatment without a screening visit. Patients will be evaluated every 3 weeks during the
study, including all safety assessments. Imaging studies will be performed every 6 - 12 weeks
during study participation. Pharmacodynamic assessments, including evaluation of the immune
response to SV-BR-1-GM will also be performed every 3 months. Patients who develop
progressive disease may remain on treatment for as long as the Investigator feels they are
deriving clinical benefit. For patients who come off treatment, a final assessment will be
carried out 2-4 weeks following the final treatment, including all safety assessments.
Off-treatment subjects will continue to be followed for survival analysis by phone call every
6 months.

Inclusion Criteria:

1. Have histological confirmation of breast cancer with recurrent and/or metastatic
lesions via investigational site which has failed prior therapy.

- Patients with persistent disease and local recurrence must not be amenable to
local treatment.

- For patients with metastatic disease:

- Human epidermal growth factor 2 (HER2) positive and estrogen receptor (ER)
or progesterone receptor (PR) positive tumors: must be refractory to
hormonal therapy (e.g., aromatase inhibitor, tamoxifen or fluvestrant) and
previously treated with at least 2 regimens including at least two anti-HER2
agents (e.g., trastuzumab and pertuzumab).

- HER2 negative and either ER or PR positive tumors: must be refractory to
hormonal therapy (e.g. aromatase inhibitor, tamoxifen or fluvestrant) and
previously treated with at least 2 chemotherapy containing regimens.

- HER2 positive and ER and PR negative tumors: must have failed at least 2
regimens including at least two anti-HER2 agents (e.g., trastuzumab and
pertuzumab).

- Triple Negative tumors: Must have exhausted other available therapies
including prior treatment with a taxane and carboplatin.

Patients with new or progressive breast cancer metastatic to brain will be eligible
provided:

1. Must have received prior radiation therapy for brain metastases or be ineligible
for radiation therapy

2. There is no need for steroids and patients have not had steroids for at least 2
weeks

3. No individual tumor size is >50 mm

4. ECOG status <3

5. Tumor is not impinging on Middle Cerebral Artery/speech-motor strip

6. If surgically debulked, must be healed from surgery and at least 3 weeks have
elapsed since general anesthesia

7. Patients consent to MRI studies at 3-4 week intervals until evidence of tumor
regression on at least 2 imaging studies. In no case, will the interval between
MRI studies be longer than 3 months. MRI study may be introduced at any time
should the patients develop new or clearly worsening symptoms and/or introduction
of steroids

2. Have evidence of persistent, recurrent, or progressive disease for which there is no
known or established treatment available with curative intent, after failing at least
one course of community standard systemic treatment with chemotherapy (and endocrine
therapy, if appropriate)

3. Be 18 years of age or older and female

4. Have expected survival of at least 4 months

5. Have adequate performance status (ECOG 0-2)

6. Have provided written informed consent

Exclusion Criteria:

1. Concurrent or recent chemotherapy, radiotherapy, immunotherapy (except the SV-BR-1-GM
regimen), or general anesthesia/major surgery within 3 weeks. Patients must have
recovered from all known or expected toxicities from previous treatment and passed a
treatment-free "washout" period of 3 weeks before starting this program (8 weeks for
persons receiving nitrosourea or mitomycin).

2. History of clinical hypersensitivity to the designated combination immunotherapy,
GM-CSF, Interferon-alpha-2b (Merck), yeast, beef, or to any components used in the
preparation of SV-BR-1-GM.

3. History of clinical hypersensitivity to the immunotherapy proposed for combination
treatment.

4. BUN >30 in conjunction with a creatinine >2.

5. Absolute granulocyte count < 1000; platelets <100,000.

6. Bilirubin >2.0; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >2x ULN.
For patients with hepatic metastases, ALT/AST >5x ULN is exclusionary.

7. Proteinuria >1+ on urinalysis or >1 gm/24hr.

8. Left ventricular ejection fraction (LVEF as determined by cardiac echo or MUGA scan)
below the normal limits of the institutions' specific testing range. This assessment
may be repeated once at the discretion of the Investigator with the approval of the
Sponsor.

9. New York Heart Association stage 3 or 4 cardiac disease.

10. A pleural or pericardial effusion of moderate severity or worse.

11. Any woman of childbearing potential (i.e., has had a menstrual cycle within the past
year and has not been surgically sterilized), unless she: agrees to take appropriate
precautions to avoid becoming pregnant (with at least 99% certainty) during the study
and has a negative serum pregnancy test within 7 days prior to starting treatment.

12. Women who are pregnant or nursing.

13. Patients with concurrent second malignancy. Persons with previous malignancies
effectively treated and not requiring treatment for >24 months are eligible, provided
there is unambiguous documentation that current local recurrence or metastatic site
represents recurrence of the primary breast malignancy.

14. Patients who are HIV positive (by self-report) or have clinical or laboratory features
indicative of AIDS.

15. Patients who require systemic steroids at doses >10 mg daily of prednisone or
equivalent or any immunosuppressive drugs. Beta-blocker therapy, while not
exclusionary, is discouraged and alternatives should be sought if possible. The
beta-blocker might compromise use of epinephrine for the rare possibility of
anaphylaxis.

16. Patients who are on treatment for an autoimmune disease, unless specifically approved
by the Investigator and the Sponsor.

17. Patients with a history of colitis.

18. Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline
personality disorder) or other clinically progressive major medical problems, unless
approved by the Investigator.

19. Male breast cancer patients.

20. Patients may not be on a concurrent clinical trial, unless approved by Investigator.