Triple Therapy for Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for a specific type of breast cancer that has either spread beyond the breast or cannot be surgically removed. The researchers aim to determine if a mix of three drugs—bicalutamide (a hormone therapy), ipilimumab, and nivolumab—can safely and effectively treat this cancer without starting with traditional chemotherapy. Women with HER2-negative breast cancer that is also androgen-receptor positive and who have not undergone more than one round of chemotherapy for metastatic cancer may qualify for this trial if they can provide a recent tumor sample. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that using the drugs nivolumab, ipilimumab, and bicalutamide together is generally safe. Studies have focused on this combination, particularly for certain types of breast cancer. Results indicate it is safe and effective for patients with HER2-negative breast cancer.

In a previous study, patients who took these drugs found the treatment well-tolerated. While some side effects occurred, most were manageable and expected with these medications. These side effects can include tiredness, skin rash, or mild diarrhea. However, they are usually not severe and can be treated or may resolve on their own.

Overall, evidence suggests that this treatment combination is safe for those considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this triple therapy for breast cancer because it combines three powerful agents: nivolumab, ipilimumab, and bicalutamide. Unlike traditional chemotherapy, which attacks cancer cells directly, nivolumab and ipilimumab are immunotherapy drugs that help the immune system recognize and attack cancer cells. Nivolumab blocks the PD-1 pathway, while ipilimumab targets CTLA-4, both of which are checkpoints that cancer cells exploit to avoid immune detection. Bicalutamide, an androgen receptor inhibitor, adds a hormone therapy component, making this combination potentially more effective against certain types of breast cancer. This multi-faceted approach could offer a more comprehensive attack on tumors, providing hope for better outcomes in patients who might not respond to standard treatments.

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

Research has shown that a combination of three drugs—nivolumab, ipilimumab, and bicalutamide—may help treat certain types of breast cancer. Participants in this trial will receive this combination therapy. Bicalutamide blocks proteins called androgen receptors, which can be effective in breast cancers with these receptors. Nivolumab and ipilimumab enhance the immune system's ability to fight cancer. Previous studies found that this drug combination can benefit patients with advanced HER2-negative breast cancer. This treatment approach aims to be more effective and long-lasting without heavy reliance on chemotherapy. ^{1 2 4 5 6}

Who Is on the Research Team?

David B. Page, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12405098/

Advances of androgen receptor in triple-negative breast ... These results suggest that the combination of enobosarm and pembrolizumab has a good safety profile but only modest efficacy. Additionally, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03650894

NCT03650894 | Nivolumab, Ipilimumab, and Bicalutamide ... To assess the 24-week clinical benefit rate of nivolumab combined with bicalutamide and ipilimumab in advanced HER2-negative breast cancers assessed by ...

3. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01852-0/fulltext

385P A phase II study of nivolumab, ipilimumab plus ... Here we report long-term outcomes and T-cell effects from a phase II trial of bicalutamide (150mg oral daily) combined with immune checkpoint blockade.

4. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PO3-06-09/743556/Abstract-PO3-06-09-A-phase-II-study-of-nivolumab

Abstract PO3-06-09: A phase II study of nivolumab plus ... The AR is expressed in 50% of hormone receptor negative (HR-) metastatic breast cancer (MBC) and >75% of HR+ MBC, and bicalutamide is clinically ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03650894?tab=table

Nivolumab, Ipilimumab, and Bicalutamide in Human ... This is a phase II open-label study of nivolumab combined with ipilimumab and bicalutamide for HER2-negative metastatic or unresectable breast cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12428055/

Unlocking the Potential of Immune Checkpoint Inhibitors in ... Immune checkpoint inhibitors (ICIs) have shown limited and inconsistent clinical activity in hormone-receptor-positive (HR+)/HER2-negative ...