Nivolumab +/- Ipilimumab for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Corticosteroids, Immunosuppressants

Disqualifiers: Metastatic disease, Prior chemotherapy, 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

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This research study is studying nivolumab, an investigational drug, in combination with ipilimumab, also an investigational drug, as a possible treatment for Squamous Cell Carcinoma of the oral cavity. The following drugs are involved in this study: * Nivolumab (Opdivo™) * Ipilimumab (Yervoy™)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take other cancer-specific therapies or certain immunosuppressive medications during the study.

What data supports the effectiveness of the drug Nivolumab +/- Ipilimumab for Head and Neck Cancer?

Research shows that Nivolumab, when used alone, can significantly reduce the risk of death and double the 1-year survival rate for patients with head and neck cancer compared to standard chemotherapy. Additionally, the combination of Nivolumab and Ipilimumab has been successful in treating a patient with refractory head and neck cancer, suggesting potential benefits of the combination therapy. ^{1 2 3 4 5}

Is the combination of Nivolumab and Ipilimumab safe for treating head and neck cancer?

Nivolumab and Ipilimumab, used for head and neck cancer, have shown an acceptable safety profile, though they can cause immune-related side effects. These treatments have been studied in various cancers, and while they can lead to immune-related adverse effects, no unexpected toxicities were reported in recent trials for head and neck cancer. ^{6 7 8 9 10}

How is the drug combination of Nivolumab and Ipilimumab unique for treating head and neck cancer?

The combination of Nivolumab and Ipilimumab is unique because it uses two different immune checkpoint inhibitors to help the body's immune system fight cancer cells more effectively. This approach is different from traditional chemotherapy and has shown success in treating other cancers like melanoma, offering a new option for patients with head and neck cancer who have limited treatment choices. ^{1 11 12 13 14}

Research Team

Jonathan Schoenfeld, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with squamous cell carcinoma of the oral cavity, who are fit for surgery and have not received certain cancer treatments or have active infections. Participants must be able to tolerate anesthesia, have no history of severe allergies to trial drugs, and women of childbearing age must use effective contraception.

Inclusion Criteria

I am 18 or older and can medically handle the treatment.

My blood tests show normal organ function and I don't have severe anemia or diabetes.

I am eligible for surgery and can undergo general anesthesia without serious risks.

Exclusion Criteria

You have had a serious allergic reaction to any kind of antibody treatment in the past.

Lack of availability for follow up assessments

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab or Nivolumab with Ipilimumab prior to surgery

2 weeks

2 visits (in-person)

Surgery

Standard of care surgery to remove cancers of the oral cavity

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 year

Treatment Details

Interventions

• Ipilimumab
• Nivolumab
• Standard of Care Surgery

Trial Overview The study is testing nivolumab alone or combined with ipilimumab against standard surgical care in treating oral cavity squamous cell carcinoma. It aims to see if these drugs can improve outcomes before patients undergo surgery.

Participant Groups

Group I: Nivolumab With Ipilimumab Experimental Treatment 3 Interventions

* Nivolumab to be delivered at a pre-determine dose for two weeks * Ipilimumab to be delivered at a pre-determine dose for one week * Blood Sample Collected * Standard of Care Surgery

Group II: Nivolumab Experimental Treatment 2 Interventions

* Nivolumab to be delivered at a pre-determine dose for two weeks * Blood Sample Collected * Standard of Care Surgery

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

Findings from Research

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]

In a phase III trial, patients with head and neck squamous cell carcinoma who were resistant to platinum-based chemotherapy and treated with nivolumab experienced a 30% lower risk of death compared to those receiving standard single-agent chemotherapy.

The 1-year survival rate for patients treated with nivolumab was twice that of those receiving traditional chemotherapy, highlighting its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

In the CheckMate 141 trial, nivolumab significantly improved overall survival (OS) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck, showing a median OS of 8.2 months for those without prior cetuximab exposure compared to 4.9 months with investigator's choice chemotherapy.

Nivolumab also demonstrated a survival benefit in patients with prior cetuximab exposure, with a median OS of 7.1 months, and had a favorable safety profile with lower rates of grade 3-4 treatment-related adverse events compared to chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use. Ferris, RL., Licitra, L., Fayette, J., et al.[2020]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

In a phase 3 trial involving 361 patients with recurrent squamous-cell carcinoma of the head and neck, nivolumab significantly improved overall survival compared to standard therapy, with a median survival of 7.5 months versus 5.1 months.

Nivolumab also had a better safety profile, with fewer severe treatment-related adverse events (13.1% vs. 35.1% in standard therapy), and patients reported stable quality of life compared to those receiving standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. Ferris, RL., Blumenschein, G., Fayette, J., et al.[2022]

In a study of 108 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab, those who experienced immune-related adverse events (irAEs) had a significantly higher objective response rate (ORR) of 46.3% compared to 19.4% in those without irAEs.

Patients with irAEs also showed longer median progression-free and overall survival rates, suggesting that the occurrence of irAEs may be a useful indicator of the treatment's effectiveness in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. Matsuo, M., Yasumatsu, R., Masuda, M., et al.[2020]

Nivolumab, a programmed death-1 checkpoint inhibitor, can lead to rare immune-related adverse effects (irAEs) such as tracheobronchial chondritis, as demonstrated in a case study of a 72-year-old man with hypopharyngeal squamous cell carcinoma.

Despite the successful treatment of his cancer, the patient experienced significant respiratory symptoms due to tracheobronchial chondritis, which was effectively managed with steroid therapy, highlighting the need for awareness of this potential complication in patients receiving nivolumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-related tracheobronchial chondritis: Extremely rare manifestation of an immune-related adverse effect. Kuba, K., Nakahira, M., Inoue, H., et al.[2021]

PD-1 inhibitors significantly improve overall survival in patients with recurrent or metastatic head and neck cancer compared to standard treatments, with a relative risk of death reduced by 40%.

Patients with human papillomavirus (HPV) positive head and neck cancer showed better response rates to PD-1/PD-L1 inhibitors than those who are HPV negative, indicating that HPV status may influence treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. Wang, BC., Cao, RB., Li, PD., et al.[2021]

Neoadjuvant immunotherapy targeting the PD-1/PD-L1 axis in head and neck cancer has shown a favorable overall objective response rate of 45.9% across eight clinical trials involving 260 patients.

Importantly, there were no deaths reported due to immune-related toxicities, indicating that this treatment approach is not only effective but also safe in the neoadjuvant setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. Amin, N., Maroun, CA., El Asmar, M., et al.[2022]

PD-1 inhibitors, used for treating recurrent or metastatic squamous cell carcinoma of the head and neck, can lead to immune-mediated adverse reactions (IMARs), highlighting the importance of monitoring patients closely.

Nurses play a crucial role in mapping patients' baseline profiles and educating them about IMARs, which helps in the timely diagnosis and management of these reactions, ultimately supporting the continuation of effective PD-1 immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 Inhibitors: Safety of Use and Management of Immune-Mediated Adverse Reactions in Patients With Head and Neck Cancer. Lewis, RL., Miller, KL.[2020]

In a study of 12 patients with recurrent and metastatic nasopharyngeal carcinoma (R/M-NPC) treated with nivolumab, the 1-year survival rate was 75.8%, indicating that this treatment can provide significant survival benefits.

Nivolumab demonstrated a modest overall response rate of 16.7% and a disease control rate of 41.7%, suggesting it is a relatively safe second-line therapy for R/M-NPC, even for patients who do not show a strong response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. Sato, H., Fushimi, C., Okada, T., 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]

In a study involving 25 patients with locally advanced or recurrent/metastatic head and neck squamous cell carcinoma, the addition of immune-checkpoint blockade (ICB) therapies like nivolumab or pembrolizumab to standard treatments did not show systematic overall survival differences, but certain cytokine levels were linked to patient outcomes.

Specifically, lower pre- and post-ICB levels of interferon-gamma (IFN-γ) were associated with better outcomes, while increases in interleukin-6 (IL-6), IL-8, and vascular endothelial growth factor A (VEGF) correlated with poorer survival, suggesting that cytokine expression patterns could help identify patients likely to benefit from ICB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome. Röhl, L., Wellhausen, J., Berszin, M., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Nivolumab Doubles Survival for Patients with HNSCC. [2019]

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

Nivolumab in Patients with Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck: Efficacy and Safety in CheckMate 141 by Prior Cetuximab Use. [2020]

4. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

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

Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. [2022]

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

Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. [2020]

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

Nivolumab-related tracheobronchial chondritis: Extremely rare manifestation of an immune-related adverse effect. [2021]

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

The effects and safety of PD-1/PD-L1 inhibitors on head and neck cancer: A systematic review and meta-analysis. [2021]

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

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]

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

PD-1 Inhibitors: Safety of Use and Management of Immune-Mediated Adverse Reactions in Patients With Head and Neck Cancer. [2020]

11. Greece pubmed.ncbi.nlm.nih.gov

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. [2021]

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

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

13. Switzerland pubmed.ncbi.nlm.nih.gov

Factors Affecting Nivolumab Therapy Outcome in Patients with Head and Neck Cancer: A Single-Center Analysis. [2022]

14. Switzerland pubmed.ncbi.nlm.nih.gov

Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome. [2023]