Bria-IMT + CPI for Advanced Breast Cancer

(BRIA-ABC Trial)

Recruiting at 16 trial locations

Overseen By Maggie Tomasini, CPM

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BriaCell Therapeutics Corporation

Must not be taking: Immunosuppressants, Steroids, others

Disqualifiers: HIV, Autoimmune disease, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: Up to 60 months

404 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the Bria-IMT regimen (also known as SV-BR-1-GM), combined with the checkpoint inhibitor Retifanlimab, can extend the lives of people with advanced, hard-to-treat breast cancer. Participants will receive either this experimental treatment or a standard treatment selected by their doctor. The trial seeks individuals with advanced breast cancer who have tried multiple therapies without success and have no other approved treatment options. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that you cannot be on certain prohibited medications. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Bria-IMT treatment is safe for people. Experts reviewed the data and found no safety issues, recommending the study continue as planned. This indicates that patients are handling the treatment well so far.

Retifanlimab, another treatment in the trial, also has a good safety record. It has been tested in other studies for conditions like Merkel cell carcinoma, a rare skin cancer. These studies reported no major safety problems, suggesting it is generally safe for people.

Overall, both treatments in this trial have demonstrated promising safety results in previous research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for advanced breast cancer because they take a novel approach by combining retifanlimab with SV-BR-1-GM, which is administered intradermally, offering a potentially more targeted and effective treatment option. Unlike standard chemotherapy or taxanes that broadly attack cancer cells, this combination engages the immune system more directly, potentially enhancing the body's own ability to fight cancer. The use of CPI infusion and interferon further boosts this immune response, potentially leading to better outcomes with fewer side effects compared to traditional treatments.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

Research has shown that the Bria-IMT treatment, which includes the SV-BR-1-GM vaccine, yields promising results for advanced breast cancer. In this trial, some participants will receive the Bria-IMT regimen alone, while others will receive it with retifanlimab, a drug that aids the immune system in fighting cancer. Studies have found that patients using the Bria-IMT treatment lived longer than those on traditional therapies. The combination of Bria-IMT with retifanlimab has also benefited patients who have already tried many other treatments. Retifanlimab alone has been effective in slowing disease progression in other types of cancer. Overall, using Bria-IMT with retifanlimab offers hopeful outcomes for people with advanced breast cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Giuseppe Del Priore, MD MPH

Principal Investigator

BriaCell Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced metastatic or locally recurrent breast cancer who have no other treatment options. Eligible patients must have failed prior therapy, not be suitable for local treatments, and meet specific criteria if they have brain metastases. They cannot join if they've had recent chemotherapy, radiotherapy, surgery, certain abnormal lab values, a history of other malignancies or immune conditions, unresolved toxicity from previous therapies, or are pregnant.

Inclusion Criteria

Have signed informed consent

My breast cancer is advanced and previous treatments didn't work.

My breast cancer has spread to my brain.

Exclusion Criteria

You are pregnant, trying to have a baby, or breastfeeding.

My side effects from previous treatments have mostly gone away.

My kidney function is within the required range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Bria-IMT regimen with or without CPI, or Treatment of Physician's Choice (TPC) in cycles every 3 weeks

Up to 60 months

Every 3 weeks

Imaging Assessment

Imaging assessments occur every 6 weeks for the first two cycles, then every 8 weeks thereafter

Up to 60 months

Every 6 weeks x2, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Interferon infiltration of the inoculation site
• Retifanlimab
• SV-BR-1-GM

Trial Overview The study compares the Bria-IMT regimen combined with retifanlimab (a checkpoint inhibitor) to treatments chosen by physicians in patients with late-stage breast cancer. It's an open-label trial where participants know which treatment they're receiving and aims to see which method improves overall survival when standard therapies aren't available.

How Is the Trial Designed?

Group I: Bria-IMT Regimen Alone Experimental Treatment 3 Interventions

The Bria-IMT regimen: Day -2 or -3 Cyclophosphamide 300mg/m2 Day 0 SV-BR-1-GM given intradermally divided into 4 inoculations Day 1-3 CPI infusion plus interferon administered intra-dermally within each SV-BR-1-GM inoculation site

Group II: Bria-IMT Regimen + CPI Experimental Treatment 4 Interventions

The Bria-IMT regimen: Day -2 or -3 Cyclophosphamide 300mg/m2 Day 0 SV-BR-1-GM given intradermally divided into 4 inoculations Day 1-3 CPI infusion plus interferon administered intra-dermally within each SV-BR-1-GM inoculation site

Group III: Treatment of Physician's Choice Active Control 1 Intervention

TPC consists of eribulin, carboplatin, capecitabine, gemcitabine, vinorelbine or taxanes in accordance with the investigators' and institutional standard of care. The specific details of the selected regimen must include every detail of administration including frequency, sequencing (for multi-agent regimens), duration of infusion or oral administration, planned dose, dose prescribed, dose administered, dose adjustments after initial prescription or start of TPC treatment, and any other change in TPC from its initial election prior to randomization.

Retifanlimab is already approved in United States for the following indications:

Approved in United States as Zynyz for:

• Merkel cell carcinoma

Who Is Running the Clinical Trial?

BriaCell Therapeutics Corporation

Lead Sponsor

Trials

4

Recruited

480+

Published Research Related to This Trial

Immunotherapy, particularly using monoclonal antibodies that target immune checkpoint receptors, has shown significant promise in improving outcomes for breast cancer patients, especially those with triple-negative breast cancer.

The combination of atezolizumab and nab-paclitaxel as a first-line treatment for metastatic triple-negative breast cancer resulted in notable improvements in progression-free survival compared to chemotherapy alone, suggesting that combining therapies may enhance effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Checkpoint Blockade Strategies in the Treatment of Breast Cancer: Where We Are and Where We Are Heading. Force, J., Leal, JHS., McArthur, HL.[2022]

The ICON trial is a pioneering study evaluating the safety and efficacy of combining checkpoint inhibitors (nivolumab and ipilimumab) with chemotherapy in patients with metastatic hormone receptor-positive breast cancer, involving 75 participants.

Preliminary evidence suggests that using anthracycline chemotherapy may enhance the immune response when paired with checkpoint inhibitors, potentially leading to improved treatment outcomes for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ICON: a randomized phase IIb study evaluating immunogenic chemotherapy combined with ipilimumab and nivolumab in patients with metastatic hormone receptor positive breast cancer. Kyte, JA., Andresen, NK., Russnes, HG., et al.[2022]

Recent advancements in therapies for advanced breast carcinoma include CDK4/6 inhibitors, oral selective estrogen receptor degraders, antibody drug conjugates, and PARP inhibitors, which have shown promising results in improving patient outcomes.

Key studies, such as the Destiny-Breast03 and RIGHT Choice studies, indicate that these new treatments may significantly alter the therapeutic landscape, offering new hope for patients facing advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update Breast Cancer 2023 Part 2 - Advanced-Stage Breast Cancer. Lux, MP., Hartkopf, AD., Fehm, TN., et al.[2023]

Recent advancements in the treatment of advanced-stage HR-positive, HER2-negative breast cancer, including the use of estrogen receptor down regulators and CDK4/6 inhibitors, have significantly improved patient outcomes.

The review highlights the importance of recent clinical trials that led to the approval of these new therapies in first-line treatment settings, reflecting a shift in management strategies for this common breast cancer subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current frontline endocrine treatment options for women with hormone receptor-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative advanced-stage breast cancer. Abdel-Razeq, H.[2019]

A feasibility study of a non-taxane triple therapy (pertuzumab, trastuzumab, and eribulin mesylate) for advanced HER2-positive breast cancer showed promising results, with no Grade 4 or 5 adverse events reported among the 10 enrolled patients.

The therapy led to significant increases in the CD8+ T cell/CD4+Foxp3+ regulatory T cell ratio, suggesting an immune response, and showed an improving trend in quality of life as measured by the FACT-B score at 3 months, indicating potential efficacy and safety for patients who cannot tolerate taxanes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab and eribulin mesylate therapy for previously treated advanced HER2-positive breast cancer: a feasibility study with analysis of biomarkers. Tono, Y., Ishihara, M., Miyahara, Y., et al.[2019]

In the FUTURE-C-Plus phase II trial, patients with advanced immune-enriched triple-negative breast cancer showed a high overall objective response rate of 81.3% when treated with a combination of camrelizumab, famitinib, and nab-paclitaxel.

The results suggest that the presence of immune cells is crucial for predicting which patients will respond well to treatments that include PD-1-targeting immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What's in a Name? That Which We Call Immune Cells by Any Other Name Would All Smell as Sweet. Salgado, R., Loi, S.[2022]

In a phase I trial involving 23 women with metastatic breast cancer, the infusion of anti-CD3 × anti-HER2 bispecific antibody-armed T cells (aATC) was found to be safe, with no dose-limiting toxicities and a maximum tolerated dose not defined, indicating a promising safety profile for this immunotherapy approach.

The treatment led to significant anti-tumor responses, with 59.1% of evaluable patients achieving stable disease and a median overall survival of 36.2 months, suggesting that aATC infusions effectively activated the immune system against breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Lum, LG., Thakur, A., Al-Kadhimi, Z., et al.[2021]

A novel tetratherapy combining a poxvirus vaccine, an anti-PD-L1 antibody, a histone deacetylase inhibitor, and a HER2-targeted drug has shown promising preclinical results in enhancing immune responses against HER2+ breast cancer, indicating potential for improved treatment outcomes.

The ongoing phase 1b clinical trial aims to evaluate the safety and efficacy of this combination therapy in advanced breast cancer, with a focus on increasing tumor immune infiltration and response rates, while monitoring changes in the tumor microenvironment and peripheral immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving the Odds in Advanced Breast Cancer With Combination Immunotherapy: Stepwise Addition of Vaccine, Immune Checkpoint Inhibitor, Chemotherapy, and HDAC Inhibitor in Advanced Stage Breast Cancer. Gatti-Mays, ME., Gameiro, SR., Ozawa, Y., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1022

Outcomes of advanced/metastatic breast cancer (aMBC) ... BRIA-IMT has shown a favorable safety profile while providing benefits to heavily treated aMBC patients. Superior outcomes and survival were seen.

2. briacell.com briacell.com/briaimt/

Bria-IMT™ | Innovative Breast Cancer Immunotherapy Recent studies showed a longer overall median survival rate in a specific group of advanced breast cancer patients when compared to traditional treatments. The ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11340742/

Results of a phase I/IIa trial of SV-BR-1-GM inoculation with ... This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the ...

4. cancernetwork.com cancernetwork.com/view/bria-imt-cancer-vaccine-shows-efficacy-tolerability-in-advanced-breast-cancer

Bria-IMT Cancer Vaccine Shows Efficacy, Tolerability in ... Overall, the objective response rate (ORR) and clinical benefit rate (CBR) were 10% and 50%. In patients with HER2-positive breast cancer, they ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06072612

NCT06072612 | Study of the Bria-IMT Regimen and CPI vs ... This is a multicenter randomized, open label study to evaluate overall survival with the Bria-IMT regimen in combination with Checkpoint Inhibitor [Retifanlimab] ...

6. briacell.com briacell.com/briacell-receives-positive-recommendation-from-data-safety-monitoring-board-dsmb-for-phase-3-study-in-metastatic-breast-cancer/

BriaCell Receives Positive Recommendation from Data ... Independent DSMB has identified no safety concerns, and recommends continuation of BriaCell's pivotal Phase 3 study of Bria-IMT™ plus immune ...

7. onclive.com onclive.com/view/dsmb-recommends-continuation-of-phase-3-study-of-bria-imt-in-metastatic-breast

DSMB Recommends Continuation of Phase 3 Study of Bria ... In the review of the data, no new safety signals were reported, and the DSMB recommended the trial continue without modifications. Bria-IMT in ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS1138

Update on phase III pivotal trial of Bria-IMT + CPI vs ... Background: The SV-BR-1-GM breast cancer cell line activates anti-tumor immunity by expressing tumor associated antigens and secreting ...

9. targetedonc.com targetedonc.com/view/bria-imt-shows-promising-os-in-advanced-metastatic-breast-cancer

Bria-IMT Shows Promising OS in Advanced Metastatic ... Updated phase 2 survival data for the investigational immunotherapy Bria-IMT indicate a meaningful overall survival (OS) advantage in patients with heavily ...