Combination Therapy for Breast Cancer

Enrolling by invitation at 13 trial locations

Overseen By Patrick W Cobb, MD, FACP

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 1 & 2

Sponsor: BriaCell Therapeutics Corporation

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, HIV, others

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

Compensation: Varies

Number of Visits: 7

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination therapy for individuals with breast cancer that has recurred or spread and who did not respond to standard treatments. The study tests the SV-BR-1-GM regimen combined with retifanlimab, an immunotherapy, to assess the safety and effectiveness of this combination. Participants will receive one of two treatment schedules to evaluate different timing strategies. The trial seeks women with recurrent or metastatic breast cancer who have tried other treatments without success and are not eligible for local treatments. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires a 'washout' period (time without taking certain medications) of 3 weeks before starting, and 8 weeks for some specific drugs. You should also avoid any medications listed as prohibited in the trial protocol.

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

Research has shown that the combination of SV-BR-1-GM and retifanlimab holds promise for treating certain types of breast cancer. Patients who had previously tried many other treatments generally tolerated this combination well. One study reported positive survival outcomes, suggesting the treatment is relatively safe.

Another study tested this combination with a drug called cyclophosphamide. This study also found the treatment tolerable for patients, with no widespread severe side effects reported, which is encouraging for those considering joining a trial.

While these findings are promising, it is important to remember that these are still early studies. More research is needed to fully understand the safety of these treatments. However, the early data appears encouraging for those seeking new options in breast cancer treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination therapy of retifanlimab and SV-BR-1-GM for breast cancer because it offers a novel approach compared to current treatments like hormone therapy, chemotherapy, and HER2-targeted therapies. Retifanlimab is an immune checkpoint inhibitor that enhances the body's immune response against cancer cells, while SV-BR-1-GM is a cancer vaccine designed to stimulate an immune attack on breast cancer cells. This combination therapy targets the immune system in a way that standard treatments do not, potentially leading to more effective and personalized cancer treatment. Additionally, the different sequences in which these therapies can be administered may provide flexibility and improved outcomes for patients.

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

This trial will evaluate two different sequences of combination therapy involving SV-BR-1-GM and retifanlimab for advanced breast cancer. Research has shown that this combination may help treat advanced breast cancer. Earlier studies found that this treatment can extend the lives of patients who have already tried many other treatments. Most patients tolerate this combination well, as it usually doesn't cause serious side effects. Specifically, patients with hormone receptor-positive advanced breast cancer have seen better results compared to past data. Overall, this treatment could offer new hope for those who haven't had success with standard therapies. ^{1 2 4 6 7}

Who Is on the Research Team?

George E Peoples, MD, FACS

Principal Investigator

LumaBridge LLC

Are You a Good Fit for This Trial?

This trial is for women over 18 with Stage IV triple-negative breast cancer that can't be treated locally and who have survived past standard therapies. They must expect to live at least 4 more months, not have severe psychiatric issues or major medical conditions, no recent immunosuppressive treatments, vaccines, transplants, or autoimmune disease treatments.

Inclusion Criteria

My cancer is not HER2 positive.

My cancer is in Stage IV.

My recurring cancer cannot be treated with surgery or radiation.

Exclusion Criteria

I have been treated for an autoimmune disease in the last 2 years.

I have a history of colitis.

I have severe psychiatric or major medical issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive the SV-BR-1-GM regimen with retifanlimab every 3 weeks, with safety evaluations and imaging studies performed periodically

12 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with survival analysis every 3 months

5 years

Every 3 months (phone call)

What Are the Treatments Tested in This Trial?

Interventions

• Retifanlimab
• SV-BR-1-GM

Trial Overview The study tests the SV-BR-1-GM regimen combined with retifanlimab on patients with advanced breast cancer. Initially tested on a small group for safety and tolerability; if successful, expanded to more patients randomized into two groups based on treatment timing.

How Is the Trial Designed?

Group I: SV-BR-1-GM, retifanlimab combination original sequence Experimental Treatment 4 Interventions

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab with cycles every 3 weeks

Group II: SV-BR-1-GM, retifanlimab combination alternative sequence Experimental Treatment 4 Interventions

Subjects will be treated with the SV-BR-1-GM regimen in combination with retifanlimab as follows: Cycle 1: SV-BR-1-GM only Cycle 2: resume retifanlimab on Day 2±1 Cycle 3 and beyond: retifanlimab can be administered on Day -2, Day 0, 1, 2, or 3.

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+

LumaBridge

Industry Sponsor

Trials

5

Recruited

380+

Cancer Insight, LLC

Industry Sponsor

Trials

10

Recruited

520+

LumaBridge

Collaborator

Trials

6

Recruited

410+

Published Research Related to This Trial

Retifanlimab is a programmed cell death 1 (PD-1) receptor-blocking antibody developed for treating solid tumors, showing promise both alone and in combination with other therapies.

It has received accelerated approval for adults with metastatic or recurrent locally advanced Merkel cell carcinoma, marking a significant milestone in its development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retifanlimab: First Approval. Kang, C.[2023]

Checkpoint immunotherapy is being explored as a new treatment for metastatic breast cancer, but single-agent therapies targeting PD1/PD-L1 or CTLA-4 have shown limited effectiveness.

Combining immunotherapy with other treatments like chemotherapy, radiotherapy, and targeted therapies may enhance cancer immunity and improve treatment outcomes, with ongoing clinical trials investigating these combination strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer. Liu, ZB., Zhang, L., Bian, J., et al.[2020]

In a phase II study involving 14 patients with metastatic castration-resistant prostate cancer, the combination of HER2 bispecific antibody-armed activated T cells and pembrolizumab showed promising efficacy, with 38.5% of patients achieving 6-month progression-free survival.

The treatment was generally safe, with only mild grade 1-2 infusion reactions reported, indicating that this combination therapy could be a viable option for further research in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer. Vaishampayan, UN., Thakur, A., Chen, W., et al.[2023]

The combination of durvalumab and tremelimumab showed improved disease control rates in patients with head and neck squamous cell carcinoma compared to tremelimumab alone, indicating its potential efficacy in this cancer type.

The combination therapy had a tolerable safety profile, with no significant increase in treatment-related adverse events compared to monotherapy, suggesting it is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab and tremelimumab combination therapy versus durvalumab or tremelimumab monotherapy for patients with solid tumors: A systematic review and meta-analysis. Wang, BC., Li, PC., Fan, JQ., et al.[2022]

In a pooled analysis of 908 patients with metastatic breast cancer, eribulin mesylate was found to be well tolerated, even after patients had undergone an average of 3.7 prior chemotherapy regimens.

The most common serious side effects included neutropenia (52.4%) and leukopenia (19.3%), but overall, the treatment was manageable with dose adjustments in a significant portion of patients (35%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of eribulin mesylate in patients with pretreated metastatic breast cancer. Goodin, S., Barbour, S., Song, J., et al.[2019]

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 phase 1 trial of LY3022855, a monoclonal antibody targeting the colony-stimulating factor-1 receptor, showed that it was well tolerated in patients with advanced solid cancers, with a recommended phase 2 dose established at 100 mg once weekly combined with durvalumab.

Despite being well tolerated, the combination treatment demonstrated limited clinical activity, with only 1.4% achieving a complete response and 2.8% a partial response among the 72 patients studied.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Falchook, GS., Peeters, M., Rottey, S., et al.[2022]

In a mouse model of breast cancer, combining the anti-PD-1 antibody with zoledronic acid (ZA) resulted in a stronger anti-tumor response compared to either treatment alone, indicating a potential synergistic effect.

The combination therapy showed no obvious toxicity, suggesting it could be a safe and effective approach for enhancing breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in combination with zoledronic acid to enhance the antitumor efficacy in the breast cancer mouse model. Li, Y., Du, Y., Sun, T., et al.[2019]

In a clinical trial involving 55 patients with advanced solid tumors, the PD-1 inhibitor dostarlimab was found to be well tolerated in both doublet and triplet combination therapies, with no new safety concerns arising.

The triplet combinations showed higher disease control rates compared to doublets, with preliminary antitumor activity observed in various combinations, indicating potential for improved efficacy in treating advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IOLite: phase 1b trial of doublet/triplet combinations of dostarlimab with niraparib, carboplatin-paclitaxel, with or without bevacizumab in patients with advanced cancer. Yap, TA., Bessudo, A., Hamilton, E., et al.[2022]

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. targetedonc.com targetedonc.com/view/bria-imt-plus-retifanlimab-shows-promising-survival-in-hr-breast-cancer

Bria-IMT Plus Retifanlimab Shows Promising Survival in ... Phase 2 data suggest a survival benefit with Bria-IMT and retifanlimab in heavily pretreated HR-positive metastatic breast cancer, outperforming historical ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03328026

Combination Study of SV-BR-1-GM With Retifanlimab This is an open-label, phase I/II double arm study of the SV-BR-1-GM regimen in combination with retifanlimab in patients with metastatic or locally recurrent ...

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 ... A phase 1/2 study showed that treatment with cyclophosphamide, SV-BR-1-GM, and retifanlimab yields favorable survival data in heavily pretreated ...

5. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/PS3-04/754031/Abstract-PS3-04-Overall-Survival-Results-of-Bria

Abstract PS3-04: Overall Survival Results of Bria-IMT ... Conclusions: In heavily pretreated MBC patients, the Bria-IMT regimen demonstrated promising results across all subtypes of breast cancer with ...

6. breastcancer.org breastcancer.org/treatment/clinical-trials/metastatic-breast-cancer-bria-imt

Bria-IMT Clinical Trial for Metastatic Breast Cancer This trial is testing whether a new cellular immunotherapy regimen called Bria-IMT is better than doctors' choice of chemotherapy for metastatic or locally ...

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 ... Phase 2 data showed a 52% 1-year overall survival rate in heavily pretreated metastatic breast cancer patients using Bria-IMT.