Bria-OTS Immunotherapy for Breast Cancer

Overseen By Blaise Bayer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BriaCell Therapeutics Corporation

Must be taking: Checkpoint inhibitors

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Concurrent cancer, Cardiac disease, others

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

Compensation: Varies

Number of Visits: 13

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open-label Phase 1/2a study. Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a clinically available check point inhibitor (CPI). During the monotherapy phase of Phase 1, one patient will be treated intradermally every 2 weeks for 6 weeks (4 doses) with an initial dose of the BC1 cell line. If this dose is tolerated, the next patient will receive an increased dose of BC1. If once again tolerated, the third patient will receive a further dose increase of the BC1. Once at least 3 patients have been safely treated with the BC1 cell line, with no dose-limiting toxicity (DLT), the combinational phase of the study will commence. Following the monotherapy phase, patients will be treated with BC1 and the Bria-OTS regimen (see below) every 3 weeks, plus a CPI at the FDA approved labelled dose and schedule. There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risk(s). During the Phase 1 combination and Phase 2 expansion phases, all patients will be treated with BC1 cells as part of the Bria-OTS regimen, which includes cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell inoculation, and peginterferon alpha-2a administered on the same day, following BC1 cell inoculation.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on any concurrent anti-cancer treatment or recent chemotherapy, radiotherapy, or other anti-cancer treatment within 3 weeks of starting the trial.

What data supports the effectiveness of the Bria-OTS treatment for breast cancer?

Research shows that cancer vaccines, which are a type of immunotherapy like Bria-OTS, have demonstrated potential benefits in treating breast cancer by stimulating the immune system to fight cancer cells. These vaccines have been shown to be safe and may improve outcomes for patients. ^{1 2 3 4 5}

Is Bria-OTS Immunotherapy for Breast Cancer safe for humans?

The safety of Bria-OTS Immunotherapy, like other cancer immunotherapies, may involve immune-related adverse events (side effects caused by the immune system attacking normal tissues), which can sometimes be serious. These events are different from those seen with traditional cancer treatments and can include autoimmune diseases, but they are generally less common. ^{6 7 8 9 10}

How is the Bria-OTS treatment different from other breast cancer treatments?

Bria-OTS is a type of immunotherapy that uses the body's immune system to target and fight breast cancer cells, which is different from traditional treatments like chemotherapy that directly kill cancer cells but can also harm healthy cells. This approach aims to reduce side effects and improve the body's natural ability to combat cancer. ^{1 3 5 11 12}

Research Team

Giuseppe Del Priore, MD, MPH

Principal Investigator

BriaCell Therapeutics Corp

Victoria Chua-Alcala, MD

Principal Investigator

Sarcoma Oncology Research Center

Eligibility Criteria

This trial is for individuals with metastatic recurrent breast cancer. Participants should be able to receive intradermal injections and have no history of severe reactions to immunotherapies. They must not have received certain treatments recently and should be in stable condition without rapidly progressing disease.

Inclusion Criteria

Have expected survival of at least 4 months

My side effects from previous treatments have mostly gone away.

My breast cancer is HER2 negative, hormone receptor positive, and has not responded to at least 2 hormone therapies.

Exclusion Criteria

History of clinical hypersensitivity to the designated therapy or any components used in the preparation of any cell line in this study

Absolute granulocyte count < 1000; platelets <50,000

Bilirubin >2.0; alkaline phosphatase >4x upper limit of normal; ALT/AST >2x ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase 1 Monotherapy

Participants receive BC1 cell line intradermally every 2 weeks for 6 weeks to assess safety and dose tolerance

6 weeks

4 visits (in-person)

Phase 1 Combination

Participants receive BC1 cells with Bria-OTS regimen and CPI every 3 weeks to assess safety and efficacy

6 weeks

2 visits (in-person)

Phase 2 Expansion

Additional subjects are treated with the Bria-OTS regimen and CPI to further evaluate safety and efficacy

9 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Every 3 months for up to 2 years (phone call or medical record review)

Treatment Details

Interventions

• BRIA-OTS Cellular Immunotherapy

Trial Overview The study tests the safety and effectiveness of BRIA-OTS cellular immunotherapy, first alone (BC1 cell line) then combined with a checkpoint inhibitor (CPI), tislelizumab. It starts with increasing doses of BC1, followed by a combination treatment including cyclophosphamide and peginterferon alpha-2a.

Participant Groups

Group I: Phase 2 Expansion Cohort Experimental Treatment 1 Intervention

Once 3 patients have been safely treated with the Bria-OTS regimen and CPI (tislelizumab) for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI). The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing. Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab).

Group II: Phase 1, Part 2 Combination Phase Experimental Treatment 1 Intervention

3 subjects will be treated every 3 weeks with the Bria-OTS regimen with a CPI (tislelizumab) in the Part 2 combination phase. The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing. Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab).

Group III: Phase 1, Part 1 Monotherapy Phase Experimental Treatment 1 Intervention

Subject 1, Q2w for 4 doses Subject 2, Q2w for 4 doses Subject 3, Q2w for 4 doses Treatment is administered every 2 weeks for a total of 4 doses. Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment. If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. A total of 3-6 subjects will be assessed for safety.

Who Is Running the Clinical Trial?

BriaCell Therapeutics Corporation

Lead Sponsor

Trials

4

Recruited

480+

Findings from Research

Breast cancer immunotherapy, particularly therapeutic vaccines, is being explored as a potential treatment option due to the severe side effects associated with conventional therapies, but no breast cancer vaccine has yet been approved for clinical use.

Current breast cancer vaccine strategies, including protein/peptide, dendritic cell, and genetic vaccines, often fail to provide clinical benefits on their own and are typically used in combination with other treatments like chemotherapy or radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence. Abbaspour, M., Akbari, V.[2022]

Immunotherapy is now a standard treatment for various cancers, including breast cancer, highlighting the role of the body's immune response in fighting tumors.

Recent clinical trials suggest that checkpoint blockade therapies can enhance the antitumor immune response, leading to meaningful improvements in patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapeutic strategies in breast cancer: A clinical update. Zhang, JQ., Plitas, G.[2022]

Breast cancer vaccines targeting antigens like HER-2/neu, MUC-1, and hTERT have shown promise in stimulating the immune system to fight cancer, with recent clinical trials indicating potential survival benefits.

These vaccines have been reported to be safe, producing minimal toxicity, which supports their continued development and use in treating breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress in the development of a therapeutic vaccine for breast cancer. Coveler, AL., Bates, NE., Disis, ML.[2021]

Advancements in gene transfer technology have opened new avenues for developing immunotherapy for breast cancer, focusing on the transfer of genes that enhance immune function and target tumor antigens.

Immunotherapy is expected to be most effective when used alongside traditional treatments, particularly in targeting micrometastatic disease to lower the chances of cancer returning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for carcinoma of the breast: Genetic immunotherapy. Strong, TV.[2019]

Immune checkpoint inhibitors have revolutionized cancer immunotherapy by reactivating T cells, leading to improved anti-tumor responses, particularly in cancers like melanoma, renal, and lung cancer.

There is growing interest in applying these immunotherapy strategies to breast cancer, with T cells being explored as both clinical markers and therapeutic options in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell-based breast cancer immunotherapy. Pilipow, K., Darwich, A., Losurdo, A.[2022]

Immune checkpoint inhibitors (ICIs) have significantly improved survival rates in patients with solid tumors by enhancing the body's anti-tumor immune response, but they can also lead to immune-related adverse events (IRAEs) that may compromise treatment continuation.

While IRAEs are generally rare compared to standard chemotherapy side effects, they can be serious, highlighting the need for careful management and understanding of these new toxicities as more combination therapies are developed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Predictable toxicities with futures immunotherapies or combinations]. Mogenet, A., Tomasini, P., Greillier, L., et al.[2020]

Cancer immunotherapies, particularly anti-CTLA4 and anti-PD1/PD-L1, are becoming more common in treatment regimens, leading to increased exposure of patients to immune-related adverse events (irAEs).

These immunotherapies can activate the immune system to fight tumors effectively, but they also have a unique toxicity profile that can cause autoimmune reactions, necessitating changes in clinical management practices to address these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Laparra, A., Champiat, S., Michot, JM., et al.[2021]

Anti-CTLA4 and anti-PD1/PD-L1 immunotherapies represent a significant shift in cancer treatment by enhancing the immune system's ability to fight tumors rather than directly targeting the tumor cells themselves.

These immunotherapies can lead to unique immune-related adverse events due to the activation of the immune system against normal tissues, necessitating changes in clinical management to address potential autoimmune reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. Champiat, S., Michot, JM., Lambotte, O.[2019]

Harnessing the immune system for cancer treatment has significantly improved patient outcomes, leading to extended life and even cures, but it can also trigger serious side effects like cytokine release syndrome and neurotoxicity.

The article reviews the biological mechanisms behind these immune-mediated adverse effects and discusses industry strategies using laboratory models to better assess safety risks in immune-oncology treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current nonclinical approaches for immune assessments of immuno-oncology biotherapeutics. Grimaldi, C., Ibraghimov, A., Kiessling, A., et al.[2023]

In a study of 260 patients with solid tumors treated with immune-oncology agents, 18.1% experienced endocrine-related adverse events (EIR-AE), primarily hypothyroidism, which were most commonly associated with nivolumab and nivolumab plus ipilimumab.

Patients who developed EIR-AE had significantly better progression-free survival (56.7 months) and overall survival (not calculable) compared to those without EIR-AE (27.7 months and 31.4 months, respectively), suggesting a potential link between these adverse events and improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine adverse events related to immune-oncology agents: retrospective experience of a single institution. España, S., Pérez Montes de Oca, A., Marques-Pamies, M., et al.[2022]

The NY-BR-1 antigen is expressed in over 80% of breast tumors and can elicit a strong immune response, making it a promising target for immunotherapy using cytotoxic T cells (CTL).

Specific CD8+ T cell responses were successfully generated against NY-BR-1 peptides, particularly the p904 epitope, which was shown to effectively recognize and target breast cancer cells, indicating its potential for T-cell-based treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1. Wang, W., Epler, J., Salazar, LG., et al.[2021]

In a proof-of-concept study involving 8 metastatic breast cancer patients, the use of activated T cells armed with bispecific antibodies (HER2 BATs) followed by immune consolidation after high-dose chemotherapy and stem cell transplant showed no significant toxicities and successfully induced anti-breast cancer immune responses.

The study found that 4 out of 6 patients who received additional infusions of unarmed T cells post-transplant exhibited increased anti-tumor activity, with a significant correlation between this activity and longer time to disease progression, suggesting that this approach may enhance immune reconstitution and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune T cells can transfer and boost anti-breast cancer immunity. Thakur, A., Rathore, R., Kondadasula, SV., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Immunotherapeutic strategies in breast cancer: A clinical update. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Progress in the development of a therapeutic vaccine for breast cancer. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Gene therapy for carcinoma of the breast: Genetic immunotherapy. [2019]

5. England pubmed.ncbi.nlm.nih.gov

T-cell-based breast cancer immunotherapy. [2022]

6. France pubmed.ncbi.nlm.nih.gov

[Predictable toxicities with futures immunotherapies or combinations]. [2020]

7. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2021]

8. France pubmed.ncbi.nlm.nih.gov

[Management of adverse events associated with cancer immunotherapy]. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Current nonclinical approaches for immune assessments of immuno-oncology biotherapeutics. [2023]

10. China pubmed.ncbi.nlm.nih.gov

Endocrine adverse events related to immune-oncology agents: retrospective experience of a single institution. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Recognition of breast cancer cells by CD8+ cytotoxic T-cell clones specific for NY-BR-1. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Immune T cells can transfer and boost anti-breast cancer immunity. [2021]