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, BriaVax) is an irradiated, allogeneic breast cancer cell-line–based immunotherapy engineered to secrete GM-CSF and to present tumor antigens via HLA class I and II. It has been studied as intradermal inoculations with a priming/boosting regimen that includes low‑dose cyclophosphamide before dosing and local interferon‑alpha after dosing; more recent studies combine it with PD‑1 inhibitors. Early-phase clinical data in heavily pretreated metastatic/advanced breast cancer suggest signals of activity, with responses enriched among patients who share specific HLA alleles with the SV-BR-1-GM line. (pubmed.ncbi.nlm.nih.gov)

Mechanism of action

• Product: An immortalized breast cancer cell line derived from HR–/HER2+ tumor, irradiated and engineered to secrete GM‑CSF, with surface HLA-I/II expression to function as an antigen‑presenting cell. The intent is to stimulate tumor‑specific T‑cell (and potentially B‑cell) responses against shared tumor antigens. (aacrjournals.org)
• Regimen: Typically cyclophosphamide 300 mg/m² IV 48–72 h before SV‑BR‑1‑GM (20×10^6 cells intradermally at multiple sites) followed by interferon‑alpha injections at the inoculation sites on days 2 and 4; schedules vary between monotherapy and combination cohorts. (ascopubs.org)
• Rationale for combinations: Treatment has been associated with increased PD‑L1 expression on circulating tumor-associated cells, providing a biologic rationale for combining with PD‑1 inhibitors (pembrolizumab or retifanlimab). (pubmed.ncbi.nlm.nih.gov)

Efficacy

• Phase I/IIa monotherapy (NCT03066947; open‑label, single‑arm; 26 enrolled, 23 inoculated; 6 U.S. centers; publication 2024): Among 16 evaluable patients with advanced, refractory metastatic breast cancer, disease control (stable disease) occurred in 8/16, and 4/16 showed objective regression of metastases (including one case with near‑complete regression of 20/20 pulmonary lesions). Clinical benefit was associated with HLA matching to SV‑BR‑1‑GM, particularly with ≥2 shared HLA alleles. Note: responses were observed in a small cohort and in a nonrandomized setting. (pubmed.ncbi.nlm.nih.gov)
• Early combination/expansion experience (NCT03328026; ongoing randomized phase 2 sequences with PD‑1 inhibitors): Meeting abstracts report “promising activity” including intracranial responses in a small post‑hoc subset with CNS metastases and signals of activity after prior antibody‑drug conjugates; detailed, peer‑reviewed response rates are not yet available. (ascopubs.org)
• Additional meeting data (SABCS/AACR): Post‑hoc analyses describe improved progression‑free survival metrics in patients with HLA matching and supportive pharmacodynamic markers; precise effect sizes are not fully reported in the abstracts. (aacrjournals.org)

Safety

• Monotherapy phase I/IIa: Six grade 4 and one grade 5 adverse events occurred but were assessed as unrelated to SV‑BR‑1‑GM. The most common treatment‑related events were local injection‑site reactions; no dose‑limiting toxicities were reported. (pubmed.ncbi.nlm.nih.gov)
• Early clinical experience/abstracts: Reports note absence of cytokine storm and no treatment‑related grade 5 events; two non‑treatment‑related grade 4 events (worsening pleural effusion, altered mental status) were described. An earlier cohort included a death due to cardiac arrest deemed unlikely related. Overall, the regimen (with cyclophosphamide and interferon‑alpha) has been described as generally well tolerated to date. (aacrjournals.org)

Development status and ongoing trials

• Monotherapy phase I/IIa (NCT03066947): Completed; results published in 2024. (pubmed.ncbi.nlm.nih.gov)
• Combination with PD‑1 inhibitors (NCT03328026): Ongoing randomized phase 2 evaluating sequencing with pembrolizumab or retifanlimab; additional institutional listings describe combinations with retifanlimab and epacadostat. Peer‑reviewed outcomes are pending. (ascopubs.org)

Further reading

• Results of the phase I/IIa monotherapy trial (peer‑reviewed, open access). Hum Vaccin Immunother. 2024. (pubmed.ncbi.nlm.nih.gov)
• ASCO 2018 meeting abstract (preliminary clinical data and regimen details). (ascopubs.org)
• AACR/SABCS 2023 abstract on whole‑cell vaccine experience and exploratory PFS findings. (aacrjournals.org)
• ASCO 2024 abstracts: intracranial metastases post‑hoc analysis; outcomes in ADC‑pretreated patients; phase 1/2 sequencing analysis. (ascopubs.org)
• Trial listings/overviews: NCT03066947 (completed) and NCT03328026 (ongoing). (pubmed.ncbi.nlm.nih.gov)

Notes: Reported efficacy derives from small, early‑phase and, in part, nonrandomized cohorts; confirmatory data are not yet available.

Last updated: Oct 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.