Triple Therapy for Breast Cancer

Recruiting at 1 trial location

Overseen By Larisa Lundgren

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Providence Health & Services

Must not be taking: Corticosteroids, Immunosuppressants, Androgen blockers

Disqualifiers: Active brain metastases, Autoimmune disease, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 24 months

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment.

What evidence supports the effectiveness of the drugs Bicalutamide, Ipilimumab, and Nivolumab in treating breast cancer?

Research shows that Nivolumab, a PD-1 inhibitor, can work well with specific immune cells to treat drug-resistant breast cancer in mice. This suggests that Nivolumab might help in treating certain types of breast cancer. ^{1 2 3 4 5}

What safety data exists for the combination of Nivolumab and Ipilimumab in cancer treatment?

The combination of Nivolumab and Ipilimumab has been studied for safety in cancer treatment, showing a higher incidence of serious side effects compared to using Nivolumab alone. Common severe side effects include increased levels of certain liver enzymes and lipase, and there is a risk of immune-related adverse events, which are side effects caused by the immune system attacking the body's own cells. ^{6 7 8 9 10}

What makes the triple therapy for breast cancer unique?

The triple therapy for breast cancer combines Bicalutamide, Ipilimumab, and Nivolumab, which is unique because it integrates hormone therapy with two types of immunotherapy. This combination aims to target cancer cells more effectively by blocking hormone receptors and enhancing the immune system's ability to fight cancer, offering a novel approach compared to traditional treatments that often focus on chemotherapy alone. ^{1 4 11 12 13}

What is the purpose of this trial?

The goal of this protocol is to evaluate the safety and efficacy of an alternative systemic combination approach that omits or delays the use of chemotherapy in metastatic disease, while improving efficacy and durability of response. The approach combines two potentially effective and previously studied strategies: androgen receptor blockade and immune checkpoint therapy.

Research Team

David B. Page, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

This trial is for women over 18 with HER2-negative breast cancer that's advanced and can't be removed by surgery or has spread (metastatic). They should have had no more than one chemotherapy treatment in the non-curative setting, must not be breastfeeding, agree to birth control measures, and have good blood and liver function. Men, pregnant women, those with certain medical conditions or a history of other cancers within the last three years are excluded.

Inclusion Criteria

I am fully active or can carry out light work.

My breast cancer cannot be removed by surgery and is not HER2 positive.

I've had only one chemotherapy treatment for my cancer that wasn't meant to cure it.

Exclusion Criteria

I have an autoimmune disease but it's under control or is one of the exceptions listed.

I have lung disease that could affect my treatment's safety monitoring.

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris, or psychiatric illness/social situations that would limit obtaining informed consent or compliance with study requirements

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a combination of nivolumab, ipilimumab, and bicalutamide until progression or unacceptable toxicity

24 months

Nivolumab every 2 weeks, Ipilimumab every 6 weeks, Bicalutamide daily

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

Open-label extension (optional)

Participants with ongoing response may continue bicalutamide and assessments as per standard of care

Long-term

Treatment Details

Interventions

• Bicalutamide
• Ipilimumab
• Nivolumab

Trial Overview The study tests combining Nivolumab and Ipilimumab (immune checkpoint inhibitors) with Bicalutamide (androgen receptor blocker) as an alternative to chemotherapy for metastatic breast cancer. It aims to see if this combination improves response without using chemo initially or delaying its need.

Participant Groups

Group I: Nivolumab, Ipilimumab, and bicalutamide Experimental Treatment 3 Interventions

Participants will receive nivolumab plus ipilimumab combination therapy. Participants should receive nivolumab at a dose of 240 milligrams (mg) fixed dose as a 30-minute intravenous (IV) infusion prepared in 50 milliliter (ml) normal saline (NS) every 2 weeks until progression. Participants should receive ipilimumab at a dose of 1 mg/kilogram as a 30-minute IV infusion prepared in 50 ml NS every 6 weeks. All subjects will take bicalutamide 150mg (3 x 50mg tablets) daily.

Bicalutamide is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Findings from Research

Triple positive breast cancers (TPBC), which express both HER-2 and hormone receptors, show unique biological characteristics that affect treatment efficacy, particularly leading to decreased effectiveness of hormonal therapies compared to HER-2-negative patients.

The study highlights the potential for improved outcomes in TPBC through tailored treatment strategies, including combinations of anti-HER-2 agents with hormonal therapy and other targeted therapies, as well as the importance of distinguishing between HER-2-positive subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer. Kolarova, I., Vanasek, J., Odrazka, K., et al.[2020]

Sacituzumab govitecan (IMMU-132) has been shown to prolong progression-free survival in patients with advanced triple-negative breast cancer, indicating its efficacy as a treatment option.

The treatment is well tolerated, resulting in fewer and more manageable side effects compared to traditional irinotecan, suggesting a safer profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ADC for Triple-Negative Breast Cancer. [2018]

In the ASCENT study involving 529 participants with metastatic triple-negative breast cancer, Sacituzumab Govitecan was found to be more effective than standard chemotherapy, leading to longer survival and greater tumor shrinkage.

While Sacituzumab Govitecan resulted in more side effects, such as neutropenia and diarrhea, supportive care helped manage these adverse effects, indicating its potential as a viable treatment option despite the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer. Bardia, A., Hurvitz, SA., Rugo, HS., et al.[2021]

Nivolumab (OPDIVO) received accelerated FDA approval for treating unresectable or metastatic melanoma based on a 31.7% objective response rate in a study of 120 patients, showing promising efficacy after prior treatments.

The treatment demonstrated durable responses, with 87% of responding patients maintaining their response for at least 6 months, although it carries risks of immune-mediated adverse reactions that were monitored in a safety assessment of 268 patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. Hazarika, M., Chuk, MK., Theoret, MR., et al.[2023]

In a meta-analysis of 48 studies involving 4,677 patients, the combination of nivolumab and ipilimumab resulted in a high incidence of adverse events (AEs), with 81.3% of patients experiencing any AE and 40.6% experiencing grade 3 or higher AEs.

The regimen of nivolumab 3 mg/kg plus ipilimumab 1 mg/kg (N3I1) was found to cause significantly fewer AEs, including serious AEs, compared to the regimen of nivolumab 1 mg/kg plus ipilimumab 3 mg/kg (N1I3), suggesting that N3I1 may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events induced by nivolumab and ipilimumab combination regimens. Somekawa, K., Horita, N., Kaneko, A., et al.[2022]

In a long-term follow-up of 94 patients with advanced melanoma treated with nivolumab and ipilimumab, the 3-year overall survival rate was 63%, indicating a promising long-term efficacy of this combination therapy.

The treatment was associated with a 42% objective response rate, but also a significant incidence of grade 3 and 4 adverse events (59%), highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. Callahan, MK., Kluger, H., Postow, MA., et al.[2021]

References

1. Czech Republic pubmed.ncbi.nlm.nih.gov

Therapeutic significance of hormone receptor positivity in patients with HER-2 positive breast cancer. [2020]

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

Dual HER2 blockade in the neoadjuvant and adjuvant treatment of HER2-positive breast cancer. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

OCT4 and SOX2 Specific Cytotoxic T Cells Exhibit Not Only Good Efficiency but Also Synergize PD-1 Inhibitor (Nivolumab) in Treating Breast Cancer Stem-Like Cells and Drug-Resistant Breast Cancer Mice. [2022]

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

An ADC for Triple-Negative Breast Cancer. [2018]

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

A plain language summary of the ASCENT study: Sacituzumab Govitecan for metastatic triple-negative breast cancer. [2021]

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

U.S. FDA Approval Summary: Nivolumab for Treatment of Unresectable or Metastatic Melanoma Following Progression on Ipilimumab. [2023]

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

A Tale of Immune-Related Adverse Events With Sequential Trials of Checkpoint Inhibitors in a Patient With Metastatic Renal Cell Carcinoma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events induced by nivolumab and ipilimumab combination regimens. [2022]

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

Nivolumab Plus Ipilimumab in Patients With Advanced Melanoma: Updated Survival, Response, and Safety Data in a Phase I Dose-Escalation Study. [2021]

10. England pubmed.ncbi.nlm.nih.gov

The efficacy and safety of Nivolumab combined with Ipilimumab in the immunotherapy of cancer: a meta-analysis. [2021]

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

Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Where Are We Now and Where Are We Headed? [2023]

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

Complete Response of Chemo-Refractory Metastatic Metaplastic Breast Cancer to Paclitaxel-Immunotherapy Combination. [2020]

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

Clinical trial data and emerging immunotherapeutic strategies: hormone receptor-positive, HER2- negative breast cancer. [2021]