Trial: Study of the Bria-IMT Regimen and CPI v…

Trial Details

Sponsor: BriaCell Therapeutics Corporation (industry)

Phase: 3

Start date: Dec. 5, 2023

Planned enrollment: 404

Trial ID: NCT06072612

More trial details at ClinicalTrials.gov

Show Summary from Sponsor

Investigational Drug AI Analysis

Show for: SV-BR-1-GM (Bria-IMT, BriaVax)

Overview

SV-BR-1-GM (also called BriaVax) is an investigational breast-cancer cell vaccine. Bria-IMT refers to a treatment regimen built around the vaccine, rather than the vaccine alone. It has been studied in people with previously treated metastatic breast cancer, including in combination with a PD-1 checkpoint inhibitor. The clinical findings remain preliminary. (pmc.ncbi.nlm.nih.gov)

Mechanism of action

SV-BR-1-GM consists of irradiated breast-cancer cells engineered to secrete GM-CSF. The cells display tumor-associated antigens through HLA molecules; the intended effect is to stimulate an immune response against a patient’s cancer. Trial regimens have also used low-dose cyclophosphamide before vaccination and local interferon-alpha afterward. Later studies added a PD-1 inhibitor to counter immune suppression. (pmc.ncbi.nlm.nih.gov)

Efficacy

In a single-arm phase I/IIa trial, 23 patients received SV-BR-1-GM without a checkpoint inhibitor. Eight of 16 patients evaluable for disease control had stable disease, and four had regression of metastases. These regressions should not be interpreted as a formal objective response rate. (pmc.ncbi.nlm.nih.gov)

A phase II conference abstract reported results for 32 heavily pretreated patients receiving the Bria-IMT regimen with retifanlimab. Median progression-free survival was 3.5 months and median overall survival was 9.5 months. Among 21 patients given the formulation selected for phase III, the reported objective response rate was 12% and the clinical benefit rate was 53%. Phase II randomization compared when checkpoint treatment began, not Bria-IMT against standard treatment; these results therefore do not establish a survival advantage over standard care. (aacrjournals.org)

Safety

In the phase I/IIa trial, injection-site irritation was the principal reported treatment-related effect. Six grade 4 events and one grade 5 event were reported, all judged unrelated to SV-BR-1-GM. In the phase II abstract, common adverse events included injection-site reactions (53%), nausea (43.8%), and fatigue (34%); 40.6% of patients experienced grade 3 or 4 adverse events. Because treatment included other drugs, these events cannot all be attributed to the vaccine. (pmc.ncbi.nlm.nih.gov)

TrialFetch AI Analysis

Goal: Determine whether Bria-IMT plus retifanlimab improves overall survival compared with physician’s-choice chemotherapy in advanced breast cancer after available treatment options have been exhausted. The study also assesses the activity of Bria-IMT without retifanlimab.

Patients: Adults with unresectable locally recurrent or metastatic breast cancer, ECOG performance status 0–2, an expected survival of at least 4 months, and no meaningful remaining approved treatment options. Prior-treatment requirements vary by tumor subtype. Patients with brain metastases may enroll if the metastases are clinically stable and do not require steroids.

Design: Multicenter, open-label, randomized study. Initial allocation is 1:1:1 to Bria-IMT plus retifanlimab, physician’s-choice treatment, or Bria-IMT alone. After the first 150 patients, the monotherapy arm closes, with crossover to combination therapy permitted if needed; subsequent allocation is 1:1 between combination therapy and physician’s-choice treatment.

Treatments: Bria-IMT is given in 3-week cycles: low-dose cyclophosphamide before intradermal SV-BR-1-GM inoculations, followed by interferon injected at the inoculation sites; the combination arm also receives the PD-1 inhibitor retifanlimab. SV-BR-1-GM is an investigational vaccine of irradiated breast-cancer cells engineered to secrete GM-CSF, intended to stimulate antitumor immune responses. Preliminary phase II combination data reported median progression-free survival of 3.5 months and median overall survival of 9.5 months in 32 heavily pretreated patients, but have not established a benefit over standard care. Physician’s-choice treatment comprises standard-of-care options such as eribulin, carboplatin, capecitabine, gemcitabine, vinorelbine, or a taxane.

Outcomes: The primary endpoint is overall survival. Secondary endpoints include progression-free survival, objective response rate, clinical benefit rate, quality of life and time without symptoms or toxicities, and CNS event-free survival. Outcomes are assessed for up to 60 months.

Burden on patient: Moderate to high for patients receiving Bria-IMT: each 3-week cycle involves treatment on multiple days, including cyclophosphamide, four intradermal vaccine inoculations, local interferon injections, and, in the combination arm, a retifanlimab infusion. Imaging is scheduled every 6 weeks for the first two assessments and every 8 weeks thereafter. Physician’s-choice treatment follows local standard-of-care schedules. No mandatory research biopsies or intensive pharmacokinetic blood sampling are specified.

Last updated: Sep 2026

Eligibility

Show Criteria

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.

Sites (79)

Sort by distance to:

Mayo Clinic-Comprehensive Cancer Center-Breast Clinic

Phoenix, Arizona, 85054, United States

[email protected] / 480-574-2802

Status: Recruiting

University of Arizona-Cancer Center

Tucson, Arizona, 85719, United States

[email protected] / 520-621-5901

Status: Recruiting

Cedars-Sinai Breast Health Services Building

West Hollywood, California, 90048, United States

[email protected] / 310-423-3713

Status: Recruiting

Cedars-Sinai Cancer Beverly Hills

Beverly Hills, California, 90211, United States

[email protected] / 310-423-3713

Status: Recruiting

Cedars-Sinai Cancer at Cedars-Sinai Medical Facility

Los Angeles, California, 90048, United States

[email protected] / 310-423-3713

Status: Recruiting

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

[email protected] / 661-862-8548

Status: Recruiting

Hoag Hospital Center

Irvine, California, 92618, United States

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

Trial Details

Show Summary from Sponsor

More details:

Investigational Drug AI Analysis

Show for: SV-BR-1-GM (Bria-IMT, BriaVax)

Overview

Mechanism of action

Efficacy

Safety

Further reading

TrialFetch AI Analysis

Eligibility

Show Criteria

Sites (79)

Mayo Clinic-Comprehensive Cancer Center-Breast Clinic

University of Arizona-Cancer Center

Cedars-Sinai Breast Health Services Building

Cedars-Sinai Cancer Beverly Hills

Cedars-Sinai Cancer at Cedars-Sinai Medical Facility

Comprehensive Blood and Cancer Center

Hoag Hospital Center

Hoag Hospital Irvine

Los Angeles Cancer Network

Los Angeles Cancer Network_Century City

Los Angeles Cancer Network_Corona

Los Angeles Cancer Network_Glendale

Los Angeles Cancer Network_Pasadena

Los Angeles Cancer Network_Valley Pres

Los Angeles cancer Network_Anaheim

Los Angeles cancer Network_Fountain Vallley

Los Angeles cancer Network_Riverside

St. John's Cancer Center

Torrance Memorial Cancer Center

UC San Diego

UCLA-Department of Medicine Hematology/Oncology-Parkside

UCLA-Hematology/Oncology Medical Plaza

UCLA-Hematology/Oncology_LA

UCLA-Hematology/Oncology_LA 2

UCLA-Hetamtology/Oncology_S Monica

Smilow Cancer Hospital at Yale New Haven

Advent Health - Orlando

Mayo Clinic Florida-Comprehensive Cancer Center

University Of Miami-SCCC-Miami

University of Miami Hospital and Clinics - Deerfield Beach

University of Miami _SCCC - Aventura

University of Miami-SCCC-Lennar

University of Miami-SCCC-Plantation

University of Miami_SCCC - Kendall

University of Miami_SCCC-Coral Springs

University of Miami_SCCC-Hollywood

Winship Cancer Institute of Emory University

Carle Foundation Cancer Institute-Urbana

Northwestern University

Southern Illinois University-Simmons

Northwest Cancer Center

AMR Kansas City Oncology

Care Access-Marrero

The Center for Cancer and Blood Disorders a division of American Oncology Partners, P.A.

Mayo Clinic-Comprehensive Cancer Center-Breast Clinic

Nebraska Cancer Specialists

Dartmouth Hitchcock Medical Center

Hunterdon Medical Center

Manhattan Hematology /Oncology Associates

NYU Langone's Perlmutter Cancer Center

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Brox)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (NY)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Babylon)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Port Jefferson Station2)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Riverhead)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(New Hyde Park)

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(Port Jefferson Station1)

New York Cancers & Blood Specialists

New York Cancers & Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Patchogue)

Regional Medical Oncology Center_Wlson

Cleveland Clinic

Gabrail Cancer & Research Center

DHR Health Oncology Institute

Mary Crowley Cancer Research

Texas Oncology - Fredericksburg