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

25 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, 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.

What data supports the effectiveness of the drug combination Nivolumab and Ipilimumab for treating salivary gland cancer?

A phase 2 trial showed that the combination of Nivolumab and Ipilimumab had limited effectiveness in adenoid cystic carcinoma but showed promise in other types of salivary gland cancers, with 16% of patients in the non-adenoid cystic carcinoma group experiencing a positive response. ^{1 2 3 4 5}

Is the combination of Nivolumab and Ipilimumab safe for treating salivary gland cancer?

In a study of 64 patients with advanced salivary gland cancer, 38% experienced serious treatment-related side effects. However, Nivolumab alone has been shown to be safe and well-tolerated in other head and neck cancers, suggesting it may be generally safe for use in humans. ^{1 2 4 6 7}

How is the drug combination of nivolumab and ipilimumab unique for treating salivary gland cancer?

The combination of nivolumab and ipilimumab is unique for treating salivary gland cancer because it targets the immune system to fight cancer cells, unlike traditional chemotherapy. This approach has shown promise particularly for non-adenoid cystic carcinoma types of salivary gland cancers, which currently lack effective treatments. ^{1 4 8 9 10}

What is the purpose of this trial?

This phase II trial studies the efficacy (the effect on the tumor) and the safety (the effect on the body) of the study drugs when given as a combination in participants with this type of cancer. Another purpose of the study is to see which tumor markers (proteins in the blood that the body produces in response to the cancer) lead to better results in participants treated with the study drugs. Nivolumab and ipilimumab are antibodies, which are human proteins that recognize and attach to a part of the tumor and/or body's immune cells. They work in slightly different ways to activate the immune system and help the body's immune system to work against tumor cells. Nivolumab and ipilimumab are investigational because they are not approved by the FDA to be used for the type of cancer being studied.

Research Team

Maria Matsangou, M.D.

Principal Investigator

Northwestern University

Eligibility Criteria

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

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

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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, 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]

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]

References

1. Greece pubmed.ncbi.nlm.nih.gov

Complete Response to Nivolumab of Resected Adenocarcinoma NOS With Parotid Gland Origin and Lung Metastasis. [2022]

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

The neutrophil-to-lymphocyte ratio in salivary gland cancers treated with pembrolizumab. [2023]

3. Greece pubmed.ncbi.nlm.nih.gov

Treatment Efficacy of PD-1 Inhibitor Therapy in Patients With Recurrent and/or Metastatic Salivary Gland Carcinoma. [2022]

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

Nivolumab plus ipilimumab in advanced salivary gland cancer: a phase 2 trial. [2023]

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

New concepts of personalized therapy in salivary gland carcinomas. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Systemic therapy for salivary gland malignancy: current status and future perspectives. [2022]

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

Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Successful Treatment of Refractory Squamous Cell Cancer of the Head and Neck with Nivolumab and Ipilimumab. [2022]

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

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

10. England 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. [2023]