Combination Therapy for Breast Cancer

Recruiting 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

36 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug combination therapy for breast cancer?

Research shows that combining immune checkpoint inhibitors, like those targeting PD-1, with other treatments can enhance the immune system's ability to fight breast cancer, especially in aggressive types like triple-negative breast cancer. This approach has shown promise in improving outcomes when used alongside chemotherapy or other targeted therapies. ^{1 2 3 4 5}

What safety data exists for the combination therapy for breast cancer?

The research articles provided do not contain specific safety data for the combination therapy involving Retifanlimab or its other names for breast cancer or other conditions. ^{3 6 7 8 9}

What makes the combination therapy for breast cancer involving Retifanlimab and SV-BR-1-GM unique?

This combination therapy is unique because it involves Retifanlimab, a drug that blocks a specific protein (PD-1) on immune cells, potentially enhancing the body's immune response against cancer cells. Retifanlimab has been approved for other cancers, like Merkel cell carcinoma, and its use in combination with SV-BR-1-GM for breast cancer represents a novel approach to potentially improve treatment outcomes by targeting immune pathways. ^{8 10 11 12 13}

What is the purpose of this trial?

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 breast cancer who have failed standard therapy. Patients will receive the SV-BR-1-GM regimen with combination immunotherapy. There will be an initial evaluation of the combination of the SV-BR-1-GM regimen with retifanlimab every 3 weeks. If this is found to be safe and well tolerated in a cohort of at least 12 patients (dose-limiting toxicities (DLTs) in less than 30% of the patients evaluated), then an expansion cohort of up to 24 patients will be treated with that combination. These will be randomized to two regimens differing in the timing of checkpoint inhibitor administration.

Research Team

George E Peoples, MD, FACS

Principal Investigator

LumaBridge LLC

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

References

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

PD-1 blockade in combination with zoledronic acid to enhance the antitumor efficacy in the breast cancer mouse model. [2019]

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

Checkpoint Blockade Strategies in the Treatment of Breast Cancer: Where We Are and Where We Are Heading. [2022]

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

Combination Strategies of Checkpoint Immunotherapy in Metastatic Breast Cancer. [2020]

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

Immune targeting in breast cancer. [2022]

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

Immunotherapy for HER2-positive breast cancer: recent advances and combination therapeutic approaches. [2022]

6. United States 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. [2023]

7. United States 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. [2022]

8. England 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. [2022]

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

Safety and tolerability of eribulin mesylate in patients with pretreated metastatic breast cancer. [2019]

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

Retifanlimab: First Approval. [2023]

11. United States 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. [2022]

12. England pubmed.ncbi.nlm.nih.gov

A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. [2022]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Emerging combination immunotherapy strategies for breast cancer: dual immune checkpoint modulation, antibody-drug conjugates and bispecific antibodies. [2022]