Randomized, Open-Label Study of the Bria-IMT Regimen and Check Point Inhibitor vs Physicians' Choice in Advanced Metastatic Breast Cancer.

More details:

Overview

SV-BR-1-GM, also known as Bria-IMT™, is an investigational immunotherapy designed for the treatment of advanced metastatic breast cancer (MBC). It involves the use of irradiated breast cancer cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), aiming to stimulate the patient's immune response against tumor cells.

Mechanism of Action

SV-BR-1-GM is derived from a breast cancer cell line that expresses human leukocyte antigen (HLA) class I and II molecules, enabling it to function as an antigen-presenting cell. By secreting GM-CSF, it recruits and activates immune cells, potentially enhancing the body's ability to recognize and attack breast cancer cells. The treatment regimen includes pre-dose low-dose cyclophosphamide and post-dose local interferon-alpha to further modulate the immune response. (pubmed.ncbi.nlm.nih.gov)

Efficacy

In a Phase I/IIa clinical trial involving 23 patients with advanced, refractory MBC, the disease control rate (stable disease) was observed in 8 of 16 evaluable patients. Notably, four patients exhibited objective regression of metastases, including one patient with near-complete regression of 20 pulmonary lesions. These responses were more pronounced in patients with HLA matches to SV-BR-1-GM. (pubmed.ncbi.nlm.nih.gov)

Another study reported a median progression-free survival (PFS) of 2.8 months for SV-BR-1-GM monotherapy and 4.2 months when combined with PD-1 inhibitors. The median overall survival was 7.0 months for monotherapy and 12.0 months for combination therapy. (aacrjournals.org)

Safety

The SV-BR-1-GM regimen has been generally well-tolerated. In the Phase I/IIa trial, there were six Grade 4 and one Grade 5 adverse events, all judged unrelated to SV-BR-1-GM. Common treatment-related adverse events included injection site reactions (39%), fatigue (26%), and nausea/vomiting (43%), mostly mild to moderate. No dose-limiting toxicities or treatment-related deaths were reported. (aacrjournals.org)

Further Reading

• Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer
• Overall survival following treatment with a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer
• Efficacy and safety of SV-BR-1-GM after progression on ADC in metastatic breast cancer patients

Last updated: Aug 2025

Last updated: Aug 2025

Inclusion Criteria:

1. Be ≥ 18 years of age.

2. Have signed informed consent.

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

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

* For patients with metastatic disease, late-stage MBC with no meaningful alternative therapies available and the following class specific treatment histories:

1. Human epidermal growth factor 2 (HER2) positive must be previously treated with at least 3 regimens containing at least two anti-HER2 and at least one chemotherapy containing regimen.

2. Estrogen receptor (ER), progesterone receptor (PR) positive tumors: must be 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 therapies including at least 2 prior chemotherapy regimens, which can include regimens 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/PR status and germline or genomic actionable targets, must also have received at least one HER2-targeted agent approved for treatment of HER2 low patients.

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 brain will be eligible provided:

* The brain metastases must be clinically stable (without evidence of progressive disease by imaging for at least 4 weeks prior to first dose)

* There is no need for steroids and patients have not had steroids for at 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 since surgery 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 days prior 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 the exception 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 successfully treated (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 stable asymptomatic endocrinopathies.

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

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

8. Serum creatinine OR Measured OR calculated Creatinine Clearance (CrCl) (GFR can also be used in place of creatinine or CrCl) \>2.0 × ULN or \<30 mL/min for participants with 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 \>5x upper 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 anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.

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

13. Proteinuria \>2+ on urinalysis

14. A history or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Screening corrected QT interval (QTc) interval \>480 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is \>480 milliseconds, the participant may enroll 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 stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible.

18. 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 during the study and has a negative serum pregnancy test within 7 days prior to starting treatment.

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

20. Women who are pregnant or nursing.

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

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

23. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive 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 immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.

25. Known active HAV, HBV, or HCV infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, anti-HCV, anti-HBc IgG or IgM, 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, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator in consultation with the Medical Monitor.

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 the Investigator.