Nivolumab + Ipilimumab for Salivary Gland Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northwestern University

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Autoimmune disease, Active infection, Heart failure, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of two investigational drugs, nivolumab and ipilimumab, in treating salivary gland cancer. These drugs are antibodies that help the immune system target and fight cancer cells. The trial aims to determine if this combination is both effective against tumors and safe for the body. Individuals with salivary gland cancer that has spread or returned, who have tried at least one other treatment, might be suitable candidates. Participants should currently have worsening cancer that is not suitable for surgery. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in cancer treatment.

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 cannot have had chemotherapy or radiotherapy within 28 days before joining the study, and you should not be on any other investigational drugs within the same timeframe. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Previous studies have tested the combination of nivolumab and ipilimumab for safety. These studies found that about 38% of patients experienced serious side effects, with common issues including immune-related problems like liver inflammation in 7% of patients. However, other studies showed the treatment was generally well-tolerated, with about 25% of patients seeing their cancer shrink or disappear. Although these drugs are not yet approved for salivary gland cancer, they have been used effectively and safely in other types of cancer. This suggests they may also be safe for salivary gland cancer, but discussing potential risks with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for salivary gland cancer, which often involve surgery, radiation, and chemotherapy, nivolumab and ipilimumab offer a fresh approach by harnessing the body's immune system. These drugs are immune checkpoint inhibitors—nivolumab targets the PD-1 pathway, while ipilimumab targets CTLA-4. This dual action potentially boosts the immune response against cancer cells more effectively than traditional methods. Researchers are excited because this combination might lead to better outcomes for patients with difficult-to-treat salivary gland cancers, offering new hope where conventional treatments fall short.

What evidence suggests that nivolumab and ipilimumab could be effective for salivary gland cancer?

Research has shown that using nivolumab and ipilimumab together may help treat salivary gland cancer. In one study, 25% of patients who took these drugs saw their tumors shrink or disappear. Participants in this trial will receive both nivolumab and ipilimumab, antibodies that enhance the immune system's ability to fight cancer. Nivolumab boosts T cells, while ipilimumab activates other immune responses. In other types of cancer, this combination has been well tolerated, with most people not experiencing severe side effects. These early results offer hope for those considering this treatment option. ^{2 5 6 7 8}

Who Is on the Research Team?

Maria Matsangou, M.D.

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for patients with metastatic or recurrent adenoid cystic carcinoma (ACC) or non-ACC salivary gland cancer who have seen their disease progress and are not candidates for surgery. They must have had at least one prior systemic therapy, measurable disease by RECIST criteria, and an ECOG status of 0-2 (3 if related to ACC).

Inclusion Criteria

There has been at least a 20% increase in the size of the tumors that can be seen in pictures or felt during an exam.

My cancer is a confirmed metastatic or recurrent salivary gland type.

My cancer is getting worse and surgery is not an option for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nivolumab and ipilimumab intravenously in courses repeating every 84 days in the absence of disease progression or unexpected toxicity

Up to 2 years

Visits on days 1, 15, 29, 43, 57, and 71 of course 1; days 1, 15, 29, and 57 of course 2; and days 1, 29, and 57 of subsequent courses

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

Follow-up every 4 weeks for 12 weeks, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab, Nivolumab

Trial Overview

The trial tests the combination of Nivolumab and Ipilimumab, both antibodies that activate the immune system against tumor cells. It aims to assess how well they work together on tumors and identify which blood tumor markers predict better outcomes.

How Is the Trial Designed?

Group I: Treatment (nivolumab, ipilimumab) Experimental Treatment 3 Interventions

Patients receive nivolumab IV over 30 minutes on days 1, 15, 29, 43, 57, and 71 of course 1 and on days 1 and 15 of course 2, over 60 minutes on days 29 and 57 of course 2 and on days 1, 29, and 57 of subsequent courses. Patients also receive ipilimumab over 90 minutes on days 1 and 43. Courses repeat every 84 days in the absence of disease progression or unexpected toxicity.

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

Approved in United States as Yervoy for:

• Melanoma
• Colorectal cancer
• Renal cell carcinoma
• Hepatocellular carcinoma
• Non-small cell lung cancer

Approved in United States as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma
• Gastric cancer
• Gastroesophageal junction cancer

Approved in European Union as Yervoy for:

• Melanoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in Canada as Yervoy for:

• Melanoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma

Approved in Japan as Yervoy for:

• Melanoma

Approved in Japan as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Classical Hodgkin lymphoma
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials

1,674

Recruited

989,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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

In a phase 2 trial involving 64 patients with metastatic salivary gland cancers, the combination of nivolumab and ipilimumab showed limited efficacy, with only 6% of patients with adenoid cystic carcinoma responding, while 16% of patients with other salivary gland cancers had objective responses.

The treatment was associated with significant safety concerns, as 38% of patients experienced severe adverse events, and the median progression-free survival was only 4.4 months for adenoid cystic carcinoma and 2.2 months for other types, indicating a need for more effective therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial. Vos, JL., Burman, B., Jain, S., et al.[2023]

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]

In a phase I study involving 24 patients with locally advanced squamous cell carcinoma of the head and neck, the combination of nivolumab and ipilimumab showed promising efficacy with a 3-year progression-free survival rate of 74% and overall survival rate of 96%.

However, the treatment was associated with significant safety concerns, as 88% of patients experienced grade 3 or higher treatment-related adverse events, including severe soft tissue ulcerations in some cases, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and ipilimumab in combination with radiotherapy in patients with high-risk locally advanced squamous cell carcinoma of the head and neck. Johnson, JM., Vathiotis, IA., Harshyne, LA., et al.[2023]

In a study of 20 patients with recurrent/metastatic salivary gland cancers treated with pembrolizumab, a higher pretreatment neutrophil-to-lymphocyte ratio (NLR) was linked to worse outcomes, indicating it could be a useful biomarker for predicting response to immune checkpoint inhibitors.

Specifically, an NLR of 5 or higher was associated with significantly increased risks of disease progression at 6 months and death at 2 years, suggesting that monitoring NLR could help identify patients who may not benefit from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab. Lee, RH., Truong, A., Wu, X., et al.[2023]

Nivolumab, a PD-1 inhibitor, has been FDA-approved for treating recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) after platinum-based therapy, but treatment options remain limited for these patients.

A case study of a 46-year-old male with refractory HNSCC showed successful treatment using a combination of nivolumab and ipilimumab, suggesting potential efficacy for this combination therapy in HNSCC, similar to its success in metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. Schwab, KS., Kristiansen, G., Schild, HH., et al.[2022]

Citations

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Nivolumab plus ipilimumab in advanced salivary gland cancer

Here we report the results of a phase 2 trial of nivo+ipi in patients with R/M SGC. These data and our analyses of serially collected tumor and blood samples ...

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This phase II trial studies nivolumab and ipilimumab in treating patients with rare tumors. Immunotherapy with monoclonal antibodies, such as nivolumab and ...

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news.bms.com

news.bms.com/news/details/2024/Bristol-Myers-Squibb-Announces-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Significantly-Improved-Overall-Survival-Compared-to-Lenvatinib-or-Sorafenib-as-First-Line-Treatment-for-Patients-with-Advanced-Hepatocellular-Carcinoma-in-CheckMate--9DW-Trial/default.aspx

Bristol Myers Squibb Announces Opdivo (nivolumab) Plus ...

Opdivo plus Yervoy demonstrated a significantly reduced risk of symptom deterioration of 24% compared to lenvatinib or sorafenib (HR: 0.76, 95% ...

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Nivolumab acts to improve the activity of T cells, thereby increasing the ability of the immune system to kill cancer cells. Ipilimumab is another type of ...

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This study retrospectively analyzes AEs related to the combined use of ipilimumab and nivolumab from 2015 to the first quarter of 2024, using ...

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OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Safety ...

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), ...

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Study Details | NCT03146650 | Nivolumab and Ipilimumab ...

Assess safety, tolerability and activity of Nivolumab and Ipilimumab in non-ACC malignant salivary gland tumors (MSGT's) using clinical benefit rate (CBR), ORR, ...