Increased Frequency of AlloStim(TM) Dosing in Combination With Cryoablation in Metastatic Breast Cancer Patients

The study will assess three different dosing schedules. A standard 3 plus 3 study design
will be used. The starting dose for each dosing schedule will be escalated in subsequent
groups of patients. The study will evaluate safety of increased frequency of AlloStim (TM)
dosing and anti-tumor effect of the new proposed dose and frequency schedule.

Inclusion Criteria:

1. Women with histologically or cytologically confirmed carcinoma of the breast.

2. Documented progressive metastatic disease not amenable to curative surgery or
radiotherapy.

3. Age ≥18 and ≤70 years

4. Patients must have prior treatments that have included capecitabine and both an
anthracycline and a taxane drug and must be resistant to taxane therapy.

1. Patients must have received a minimum cumulative dose of anthracycline (≥ 180
mg/m² of doxorubicin or ≥ 300 mg/m² of epirubicin) or be resistant to an
anthracycline and resistant to capecitabine and anti-hormonal therapy (ER+
patients).

2. Resistance is defined as tumor progression while receiving treatment or
progression within 4 months of the last dose in the metastatic setting, or
recurrence within 12 months in the neoadjuvant or adjuvant setting.

5. Post-menopausal ER+ and/or PR+ patients must have received at least two lines of
prior anti-estrogen therapy, which includes an aromatase inhibitor.

6. Her2+ patients must have received at least one Her2+ targeted regimen containing
trastuzumab alone or with pertuzumab or with lapatinib. Patients who have been
treated with trastuzumab or pertuzumab must have discontinued therapy at least 4
weeks prior to study treatment.

7. Prior radiation therapy must be completed at least 4 weeks before treatment.

8. Measurable disease according to revised RECIST v.1.1 guidelines with at least one
lesion deemed to be safely accessible for serial biopsy.

9. ECOG <2

10. Adequate hematological function

1. Absolute granulocyte count ≥ 1,500/mm3

2. Platelet count ≥ 100,000/mm3

3. PT/INR ≤ 1.5

4. INR correctable to ≤ 1.5 or a PT/PTT correctable to normal limits. Patients
receiving anti-coagulation treatment with an agent such as warfarin or heparin
may be allowed to participate. For patients on warfarin, the INR should be
monitored weekly prior to any intervention to assure INR is stable. However,
heparin or warfarin must be withheld prior to biopsy such that the above
criteria are met.

5. Hemoglobin ≥ 9 g/dL (may be corrected by transfusion)

11. Adequate organ function.

1. Creatinine ≤ 1.5 mg/dL

2. Total bilirubin ≤ 1.5 times upper limit of normal (ULN)

3. Alkaline phosphatase ≤ 2.5 times ULN (≤ 5 times normal if liver involvement)

4. Aspartate aminotransferase (AST) or (SGOT) ≤ 5.0 times ULN

5. Alanine aminotransferase (ALT) or (SGPT) ≤ 5.0 times ULN

12. EKG without clinically relevant abnormalities

13. Pre-menopausal patients with child bearing potential must agree to use adequate
contraception.

14. Study specific informed consent in the native language of the subject.

Exclusion Criteria:

1. Peritoneal carcinomatosis.

2. Moderate to large ascites accumulation requiring or likely to require paracentesis.

3. Clinical evidence or radiological evidence of brain metastasis or leptomeningeal
involvement.

4. Pulmonary lymphangitis or symptomatic pleural effusion (grade ≥ 2) that results in
pulmonary dysfunction requiring active treatment.

5. History of second primary malignancy, except: bilateral breast carcinoma, in situ
carcinoma of the cervix, adequately treated non-melanomatous carcinoma of the skin,
and other malignancy treated at least 5 years previously with no evidence of
recurrence.

6. Patients having received > 3 regimens of prior chemotherapy for metastatic disease.

7. History of severe hypersensitivity to monoclonal antibody drugs or any
contraindication to any of the study drugs.

8. Pregnant or breast feeding.

9. Patients who have any serious, concurrent uncontrolled medical disorder.

10. Prior hepatectomy, liver chemoembolization, liver cryoablation or radiofrequency
ablated.

11. Symptomatic pulmonary disease.

12. Bevacizumab (Avastin®) within 3 weeks of accrual.

13. Prior allogeneic bone marrow/stem cell or solid organ transplant.

14. Chronic use (> 2 weeks) of greater than physiologic doses of a corticosteroid agent
(dose equivalent to > 10 mg/day of prednisone) within 30 days of the first day of
investigational product treatment.

- Topical and inhaled corticosteroids are permitted

15. Concomitant active autoimmune disease (e.g., rheumatoid arthritis, multiple
sclerosis, autoimmune thyroid disease, uveitis).

16. Prior experimental therapy or cancer vaccine treatment (e.g., dendritic cell therapy,
heat shock vaccine).

17. Current immunosuppressive therapy, including: cyclosporine, antithymocyte globulin,
or tacrolimus within 1 month of study entry.

18. History of blood transfusion reactions.

19. Known allergy to bovine products.

20. Know allergy to murine products.

21. Progressive viral or bacterial infection

- All infections must be resolved and the patient must remain afebrile for seven days
without antibiotics prior to being placed into the study

22. Cardiac disease of symptomatic nature or cardiac ejection fraction < 45%.

23. History of HIV positivity or AIDS.

24. Psychiatric or addictive disorders or other condition that, in the opinion of the
investigator, would preclude study participation.

25. Concurrent medication known to interfere with platelet function or coagulation (e.g.,
aspirin, ibuprofen, clopidogrel, or warfarin) unless such medications can be
discontinued for an appropriate time period based on the drug half-life and known
activity (e.g., aspirin for 7 days) prior to cryoablation procedure.

26. Use of low molecular weight heparin preparations unless can be discontinued 8 hours
prior to cryoablation.