Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer.

Inclusion Criteria:

1. Be ≥ 18 years of age.

2. Have signed informed consent.

3. Have histological confirmation of breast cancer with either locally recurrentunresectable and/or metastatic lesions, and have failed prior therapy:

• Patients with persistent disease and local recurrence must not be amenable tolocal treatment.

• For patients with metastatic disease, late-stage MBC with no meaningfulalternative therapies available and the following class specific treatmenthistories:

1. Human epidermal growth factor 2 (HER2) positive must be previously treatedwith at least 3 regimens containing at least two anti-HER2 and at leastone chemotherapy containing regimen.
2. Estrogen receptor (ER), progesterone receptor (PR) positive tumors: mustbe refractory to hormonal therapy demonstrated by progression on at least 2 hormonal agents in 2 separate lines of hormone directed therapy.
3. Triple Negative tumors: Must have exhausted all curative intent therapiesincluding at least 2 prior chemotherapy regimens, which can includeregimens in neoadjuvant and adjuvant settings.
4. Cancers with known germline or genomic actionable targets, e.g. g/mBRCA,must have been treated with all tumor directed indicated treatment e.g.PARPi, if tolerated.
5. HER2 low patients, in addition to the appropriate therapies based on ER/PRstatus and germline or genomic actionable targets, must also have receivedat least one HER2-targeted agent approved for treatment of HER2 lowpatients.
6. HER2 negative tumors must be refractory to hormonal therapy (if indicated)and previously treated with at least 2 chemotherapy regimens.
7. Patients with new or progressive breast cancer metastatic to the brainwill be eligible provided:

• The brain metastases must be clinically stable (without evidence ofprogressive disease by imaging for at least 4 weeks prior to firstdose)
• There is no need for steroids and patients have not had steroids forat least 2 weeks prior to the first dose
• Tumor is not impinging on Middle Cerebral Artery/speech-motor strip
• If surgically debulked, must be healed with at least 3 weeks sincesurgery prior to the first dose

4. Has expected survival of at least 4 months.

5. ECOG performance status of 0, 1 or 2

Exclusion Criteria:

1. Concurrent or recent chemotherapy, immunotherapy or major surgery within 21 daysprior to the first dose.

2. Radiotherapy within 14 days of the first dose of study treatment.

3. Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with theexception of any grade of alopecia and anemia not requiring transfusion support).

4. Any toxicity to prior CPI that was grade 3 or higher unless it has been successfullytreated (e.g. hypothyroidism or hypopituitarism treated with replacement therapy), .

5. Toxicity to prior CPI that has not resolved to grade 1 or less except for stableasymptomatic endocrinopathies.

6. History of clinical hypersensitivity to the designated therapy as specified in theprotocol, including the proposed TPC, beef, or to any components used in thepreparation of SV- BR-1-GM.

7. History of hypersensitivity to any of the therapies proposed for treatment in thisstudy.

8. Serum creatinine OR Measured OR calculated Creatinine Clearance (CrCl) (GFR can alsobe used in place of creatinine or CrCl) >2.0 × ULN or <30 mL/min for participantswith creatinine levels >2.0 × institutional ULN.

9. Absolute granulocyte count <1000; platelets <80,000; hemoglobin ≤ 7 g/L.

10. Bilirubin ≥ 2 × ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase >5xupper limit of normal (ULN); ALT/AST >3x ULN. For patients with hepatic metastases,ALT/AST >5x ULN is exclusionary.

11. INR or PT or aPTT > 1.8 × ULN, unless the participant is receiving anticoagulanttherapy as long as PT or aPTT is within therapeutic range of intended use ofanticoagulants.

12. Receiving any medication listed in the prohibited medication section of theprotocol.

13. Proteinuria >2+ on urinalysis

14. A history or presence of an abnormal electrocardiogram (ECG) that, in theInvestigator's opinion, is clinically meaningful. Screening corrected QT interval (QTc) interval >480 milliseconds is excluded (corrected by Fridericia or Bazettformula). In the event that a single QTc is >480 milliseconds, the participant mayenroll if the average QTc for the 3 ECGs is <480 milliseconds.

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

16. A pericardial effusion of moderate severity or worse.

17. Symptomatic pleural effusion or ascites. A participant who is clinically stablefollowing treatment for these conditions (including therapeutic thoraco- orparacentesis) is eligible.

18. Any woman of childbearing potential (i.e., has had a menstrual cycle within the pastyear and has not been surgically sterilized), unless she agrees to take appropriateprecautions to avoid becoming pregnant during the study and has a negative serumpregnancy test within 7 days prior to starting treatment.

19. Men must have been sterile or, if they were potentially fertile/reproductivelycompetent, should take appropriate precautions to avoid fathering a child for theduration of the study.

20. Women who are pregnant or nursing.

21. Known additional malignancy that is progressing or requires active treatment, orhistory of other malignancy within 2 years of study entry with the exception ofcured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer,prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or othernoninvasive or indolent malignancy, or cancers from which the participant has beendisease-free for > 1 year, after treatment with curative intent.

22. Patients who have uncontrolled HIV or have clinical or laboratory featuresindicative of AIDS.

23. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroidtherapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form ofimmunosuppressive therapy within 7 days prior to the first dose of study treatment.

24. Have an active autoimmune disease that has required systemic treatment in past year (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressivedrugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroidreplacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.

25. Known active HAV, HBV, or HCV infection, as defined by elevated transaminases withthe following serology: positivity for HAV IgM antibody, anti-HCV, anti-HBc IgG orIgM, or HBsAg (in the absence of prior immunization).

26. Active infections requiring systemic therapy within the past 14 days.

27. Patients with severe psychiatric disease (e.g., schizophrenia, bipolar, orborderline personality disorder) or other clinically progressive major medicalproblems, unless approved by the Investigator in consultation with the MedicalMonitor.

28. Has received a live vaccine within 28 days of the first dose of study drug.

29. Patients may not be on a concurrent clinical trial, unless approved by theInvestigator.