Dendritic Cell Therapy for Brain Metastases From Breast- or Lung Cancer

Inclusion Criteria:

1. Willing and able to provide informed consent

2. Age between 18 and 75 years (inclusive) at screening.

3. Willingness to provide Social Security Number to facilitate survival follow up.

4. Pathologically confirmed metastatic breast or non-small cell lung cancer

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2

6. Adequate bone marrow function, as indicated by the following:

7. Adequate renal function

8. Adequate liver function

9. Life expectancy > 12 weeks

10. Negative serum pregnancy test done ≤7 days prior to registration, for women of
childbearing potential only.

11. Determined prior to enrollment: sufficient number of doses of DCVax-Direct
manufactured to complete 7 injections. A second leukapheresis is allowed to meet this
requirement if necessary.

12. Unequivocal evidence of newly diagnosed untreated brain metastases and/or progressive
brain metastases after previous whole brain radiation therapy (WBRT), currently
amenable to stereotactic radiosurgery

13. At least one CNS metastasis accessible for reservoir placement

14. At least one measurable CNS metastasis (lesion ≥ 10 mm per RANO-BM criteria)

Exclusion Criteria:

1. Receiving any other investigational agent which would be considered as a treatment for
the primary neoplasm OR Participated in a study of an investigational agent, received
study therapy or used an investigational device ≤4 weeks prior to registration

2. Immunocompromised patients and patients with known immunodeficiency

3. Patients receiving systemic steroid therapy >10 mg prednisone or equivalent or any
other immunosuppressive therapy ≤7 days prior to registration. NOTE: Inhaled steroids
and low-dose corticosteroids are allowed.

4. History of active tuberculosis (TB), human immunodeficiency virus (HIV), active
hepatitis B (e.g., HBsAg reactive) and/or active hepatitis C infection (e.g. HCV RNA
qualitative is detected).

5. Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use
of disease modifying agents, corticosteroids or immunosuppressive drugs). NOTE:
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

6. Known history of, or any evidence of active, non-infectious pneumonitis.

7. Active infection requiring systemic therapy.

8. Other active malignancy ≤3 years prior to registration. EXCEPTIONS: Adequately treated
non-melanotic skin cancer (adequate wound healing is required prior to study entry) or
carcinoma-in-situ of the cervix. NOTE: If there is a history of prior solid tumor
malignancy, it must have been treated curatively with no evidence of recurrence ≤3
years prior to registration.

9. Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns or compliance
with clinical study procedures, e.g., infection/inflammation, intestinal obstruction,
unable to swallow medication, social/ psychological issues, etc.

10. Medical, psychiatric, cognitive or other conditions that may compromise the patient's
ability to understand the patient information, give informed consent, comply with the
study protocol or complete the study.

11. Stage IV lung cancer patients with actionable EGFR, ALK or ROS-1 alteration will be
excluded from the study.

12. Serious medical conditions

13. Any systemic myelotoxic chemotherapy within 8 weeks prior to screening

14. Evidence of recent hemorrhage on MR at pre-screening

15. Positive HIV-1, HIV-2, or HTLV-I/II tests.

16. History of multiple sclerosis

17. Requirement for ongoing immunosuppressants

18. Ongoing medical need for continuous anti-coagulation or anti-platelet medication,

19. Known genetic cancer-susceptibility syndromes such as Li-Fraumeni syndrome

20. Ongoing fever for longer than 48 hours of ≥ 101.5oF/38.6oC at screening

21. Females of child-bearing potential who are pregnant or lactating or who are not using
adequate contraception.

22. Allergy or anaphylaxis to any of the reagents used in this study

23. Inability or unwillingness to return for required visits and follow-up exams