Nivolumab + Ipilimumab for Breast Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Brain metastases, Active infection, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 18

Duration: 9.7 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, nivolumab (Opdivo) and ipilimumab (Yervoy), to determine their effectiveness in treating a type of breast cancer lacking excess HER2 protein and characterized by many genetic mutations. The goal is to explore whether these drugs, commonly used in cancer immunotherapy, can control or reduce these specific breast cancer tumors. Suitable candidates include patients with confirmed invasive breast cancer that has metastasized and lacks the HER2 protein but has a high number of genetic mutations. As a Phase 2 trial, this 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, you must stop any chemotherapy, biologic therapy, or other anti-cancer treatments at least 14 days before starting the trial. You can continue bisphosphonate therapy if you are already on it.

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

Research has shown that the combination of nivolumab and ipilimumab has been tested in various cancer types. These studies found that while the treatment can be effective, it might also cause serious side effects.

For instance, some patients experienced serious or life-threatening issues. However, these reactions do not occur in everyone, and results can vary from person to person. Both drugs have already received FDA approval for other uses, indicating they have passed strict safety tests.

In one study, this drug combination showed promising results for patients with a rare type of breast cancer called metaplastic breast cancer. This suggests it might also benefit other types of breast cancer, such as the hypermutated HER2 negative type being examined in this trial.

Overall, while the combination has shown promise, participants must understand the potential risks and discuss them with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining Nivolumab and Ipilimumab for breast cancer because these drugs work by harnessing the body's immune system to attack cancer cells. Unlike traditional chemotherapy, which directly kills cancer cells but can also harm healthy cells, these drugs are part of a class called immune checkpoint inhibitors. They target and block specific proteins that prevent the immune system from attacking cancer cells, potentially leading to a more targeted and less toxic treatment option. This approach not only aims to improve the effectiveness of treatment but also to enhance the body's natural immune response against cancer.

What evidence suggests that this treatment might be an effective treatment for hypermutated HER2 negative breast cancer?

Research has shown that using nivolumab and ipilimumab together holds potential for treating some cancers. In studies, 26% of patients experienced a complete response, with their cancer disappearing, while 30% had a partial response, with their cancer shrinking. This trial will evaluate the combination of nivolumab and ipilimumab for breast cancer, including metaplastic breast cancer, a rare form of the disease. Additionally, patients who received both drugs in previous studies lived longer over five years compared to those who received just one drug. This suggests the combination might also be effective for hypermutated HER2-negative breast cancer. ^{1 2 3 4 5}

Who Is on the Research Team?

Sara Tolaney, MD, MPH

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with metastatic HER2-negative breast cancer that's hypermutated (TMB ≥9 mutations/megabase). They can have had up to three prior chemo treatments and must be off chemo for at least 14 days. Participants need functioning major organs, no severe illnesses, not pregnant or breastfeeding, and agree to use effective contraception.

Inclusion Criteria

I have recovered from previous cancer treatment side effects, except for hair loss and numbness.

I am mostly able to care for myself and carry out daily activities.

My breast cancer is HER2-negative and may be hormone receptor positive or negative.

Exclusion Criteria

I have not received a live vaccine in the last 28 days.

I have not taken any other cancer treatments in the last 14 days.

I do not have any other cancer needing treatment at the same time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab intravenously every 2 weeks and ipilimumab every 6 weeks

9.7 months

Bi-weekly visits for nivolumab, every 6 weeks for ipilimumab

Follow-up

Participants are monitored for overall survival and response rate every 12 weeks

2 years

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab

Trial Overview The study tests a combination of two drugs: Nivolumab (Opdivo) and Ipilimumab (Yervoy), as potential treatment for this type of breast cancer. It includes patients who've tried other treatments without success and measures the effectiveness of these drugs in controlling the disease.

How Is the Trial Designed?

Group I: Nivolumab+Ipilimumab Experimental Treatment 2 Interventions

* Ipilimumab is administered intravenously every 6 weeks * Nivolumab is administered intravenously every 2 weeks

Ipilimumab is already approved in United States, European Union for the following indications:

Approved in United States as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Approved in European Union as Yervoy for:

• Advanced melanoma
• Stage III unresectable melanoma
• Stage IV metastatic melanoma

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

Published Research Related to This Trial

Nivolumab combined with ipilimumab significantly improves treatment outcomes in cancer, showing higher rates of complete response (CR), partial response (PR), and overall response rate (ORR) compared to either drug alone, based on a meta-analysis of 11 studies.

While the combination therapy N1I3 (1 mg/kg nivolumab and 3 mg/kg ipilimumab) was more effective than N3I1 (3 mg/kg nivolumab and 1 mg/kg ipilimumab), it also had a higher incidence of serious adverse events, though overall safety was still considered acceptable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of combined immune checkpoint inhibitors (nivolumab plus ipilimumab): a systematic review and meta-analysis. Chen, J., Li, S., Yao, Q., et al.[2021]

Nivolumab plus ipilimumab showed durable and long-term efficacy in treating advanced non-small cell lung cancer (NSCLC) compared to chemotherapy, regardless of tumor PD-L1 expression levels.

These findings are based on updated results from part 1 of the phase 3 CheckMate 227 trial, indicating that this combination therapy could be a more effective frontline treatment option for NSCLC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab/Ipilimumab Combo Yields Durable Efficacy in Advanced NSCLC. Kahl, KL.[2021]

Combined immune checkpoint blockade (ICB) using nivolumab and ipilimumab shows significant efficacy in treating advanced melanoma, but it also leads to a higher frequency and severity of adverse drug reactions (ADRs) compared to single-agent therapies, based on pooled safety data from 1551 patients.

Most immune-related ADRs are reversible with glucocorticoids, but due to the increased risk and rapid onset of these toxicities, clinicians must be well-trained to monitor and manage these side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined immune checkpoint blockade (anti-PD-1/anti-CTLA-4): Evaluation and management of adverse drug reactions. Hassel, JC., Heinzerling, L., Aberle, J., et al.[2022]

In a study analyzing 2,088 individual case safety reports (ICSRs) related to immune checkpoint inhibitors (ICIs) in Italy, 801 reports documented serious immune-related adverse drug reactions (irADRs), primarily affecting male patients with gastrointestinal and skin toxicities.

Among the ICIs, nivolumab and pembrolizumab were most frequently associated with irADRs, with significant risks identified for pembrolizumab and ipilimumab, highlighting the need for oncologists to recognize and manage these serious side effects effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Inhibitors and Immune-Related Adverse Drug Reactions: Data From Italian Pharmacovigilance Database. Ruggiero, R., Fraenza, F., Scavone, C., et al.[2022]

A systematic review of 14 randomized controlled trials found that combining nivolumab (NIVO) with ipilimumab (IPI) significantly increases the risk of treatment-related adverse events (TRAEs) compared to NIVO alone, with an overall risk ratio of 1.11 for any grade TRAEs and 1.95 for severe (grade 3 or 4) TRAEs.

Specific adverse events were notably higher with the combination therapy, including colitis (RR = 4.52), pneumonitis (RR = 3.06), and diarrhea (RR = 1.68), indicating that while the combination may be effective, it comes with increased safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Induced by Nivolumab Plus Ipilimumab vs. Nivolumab Monotherapy among Cancer Patients: A Systematic Review and Meta-Analysis. Kamat, S., Patel, J., Brown, BR., et al.[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]

Combining nivolumab with ipilimumab results in higher response rates in cancer treatment compared to using nivolumab alone, indicating a potentially more effective therapeutic strategy.

This combination therapy may enhance the immune response against cancer, but specific details on the number of subjects or study duration are not provided in the abstract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus Ipilimumab Achieves Responses in dMMR/MSI-H Tumors. [2019]

In a pooled analysis of 1332 patients with advanced non-small-cell lung cancer (NSCLC), the combination of nivolumab and ipilimumab showed a median overall survival (OS) of 18.6 months and a 3-year OS rate of 35%, indicating significant long-term survival benefits compared to traditional chemotherapy.

The study found that patients who responded to treatment at 6 months had markedly better survival rates, with a 3-year OS of 66% for responders, highlighting the importance of early response in predicting long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis. Borghaei, H., Ciuleanu, TE., Lee, JS., et al.[2023]

In a phase 1 trial involving 53 patients with advanced melanoma, the combination of nivolumab and ipilimumab resulted in a 40% objective response rate, with 65% of patients showing clinical activity, indicating significant effectiveness in tumor reduction.

The concurrent treatment had a manageable safety profile, with 53% of patients experiencing grade 3 or 4 adverse events, which were similar to those seen with monotherapy and generally reversible, suggesting that this combination therapy is a viable option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced melanoma. Wolchok, JD., Kluger, H., Callahan, MK., et al.[2022]

Nivolumab combined with ipilimumab significantly improves overall survival in adult patients with intermediate/poor-risk advanced renal cell carcinoma compared to sunitinib, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death.

In the study involving 1096 patients, the median overall survival was not reached for the nivolumab + ipilimumab group, while it was 25.95 months for the sunitinib group, highlighting the potential of this combination therapy for better long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

European Medicines Agency extension of indication to include the combination immunotherapy cancer drug treatment with nivolumab (Opdivo) and ipilimumab (Yervoy) for adults with intermediate/poor-risk advanced renal cell carcinoma. Ali, S., Camarero, J., Hennik, P., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352976/

Combination of Ipilimumab and Nivolumab in Cancers Their results showed 26% complete response (CR), 30% partial response (PR), and the rate of SD was 2% for six months. Nivolumab combined with ipilimumab had ...

2. onclive.com onclive.com/view/nivolumab-ipilimumab-combo-shows-promise-in-metaplastic-breast-cancer

Nivolumab/Ipilimumab Combo Shows Promise in ... The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) showed early promising activity in patients with metaplastic breast cancer.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910836

Five-Year Survival with Combined Nivolumab and ... Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group.

4. news.bms.com news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-First-Line-Treatment-for-Unresectable-or-Metastatic-Hepatocellular-Carcinoma/default.aspx

U.S. Food and Drug Administration Approves Opdivo ... Based on the Phase 3 CheckMate-9DW trial, Opdivo plus Yervoy demonstrated a statistically significant overall survival benefit compared to ...

5. opdivo.com opdivo.com/clinical-trial-results

Clinical Trial Results OPDIVO® (nivolumab) is a prescription medicine used in combination with YERVOY® (ipilimumab) as a first treatment for adults with a type of cancer that affects ...