Nivolumab + Lirilumab for Head and Neck Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunotherapy, Corticosteroids

Disqualifiers: Autoimmune conditions, Brain metastases, 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: 30

29 Participants Needed

Trial Summary

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 be on long-term corticosteroids at high doses, and you must not have had recent chemotherapy, radiotherapy, or certain immunotherapies. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Nivolumab for head and neck cancer?

Nivolumab has been shown to improve overall survival in patients with recurrent or metastatic head and neck squamous cell carcinoma who have progressed after platinum-based chemotherapy, offering a promising option for those with limited treatment choices. ^{1 2 3 4 5}

Is the combination of Nivolumab and Lirilumab safe for humans?

Nivolumab, used for head and neck cancer, can cause immune-related side effects, which are reactions where the immune system attacks normal organs and tissues. These side effects are generally manageable, but they can be serious in some cases. ^{3 6 7 8 9}

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

The combination of Nivolumab and Lirilumab is unique because it uses dual immune-checkpoint inhibition, targeting both PD-1 and KIR pathways, to potentially improve disease-free survival in patients with recurrent, resectable squamous cell carcinoma of the head and neck, especially when used before and after surgery. ^{3 4 10 11 12}

What is the purpose of this trial?

This research study is studying a combination of two immunotherapy drugs, as a possible treatment for locoregionally recurrent squamous cell carcinoma of the head and neck. The immunotherapy drugs involved in this study are: * Nivolumab (Opdivo™) * Lirilumab

Research Team

Glenn J. Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

Adults with confirmed recurrent squamous cell carcinoma of the head and neck, who can provide tissue samples, have not had certain treatments recently, and are in relatively good health. Women must use contraception and have a negative pregnancy test; men must also agree to use effective birth control.

Inclusion Criteria

leukocytes ≥3,000/mcL

AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the start of nivolumab

Exclusion Criteria

I have an autoimmune condition but am stable, not on high-dose steroids for over 4 weeks.

I do not have any serious illnesses or social situations that would stop me from following the study's requirements.

I have been treated with immunotherapy targeting cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive a single dose of Nivolumab and Lirilumab prior to salvage surgical resection

Up to 23 days

1 visit (in-person)

Surgery

Participants undergo salvage surgical resection

1 day

1 visit (in-person)

Adjuvant Treatment

Nivolumab and Lirilumab administered in cycles post-surgery

Up to 28 months

Every 28 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 months

Treatment Details

Interventions

• Lirilumab
• Nivolumab
• Surgery

Trial Overview The trial is testing a combination of two immunotherapy drugs called Nivolumab (Opdivo™) and Lirilumab as potential treatments for head and neck cancer before and after surgery.

Participant Groups

Group I: Nivolumab+Lirilumab Experimental Treatment 2 Interventions

* The drugs will be administered intravenously. A single dose of Nivolumab and Lirilumab will be administered prior Salvage surgical resection. * In Cycle 1-3: Nivolumab will be administered on Days 1 and 15 and lirilumab will be administered on Day 1 of each 28 day long cycle * In Cycle 4-6 and beyond: Nivolumab and lirilumab will be administered on Day 1 of each 28 day long cycle.

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

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 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]

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 the phase II HAWK study involving 112 patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) who had high PD-L1 expression, durvalumab showed an objective response rate of 16.2%, with a notably higher rate of 29.4% in HPV-positive patients.

Durvalumab was found to have an acceptable safety profile, with 57.1% of patients experiencing treatment-related adverse events, but none were fatal, indicating it could be a viable treatment option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Zandberg, DP., Algazi, AP., Jimeno, A., et al.[2020]

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]

In a phase II trial involving 41 patients with operable head and neck squamous cell carcinoma (HNSCC), preoperative treatment with olaparib, either alone or in combination with cisplatin or durvalumab, was found to be safe and resulted in a significant reduction in tumor cell proliferation, as indicated by a decrease in Ki67 of at least 25% in 44.8% of treated patients.

The treatment also modulated the tumor microenvironment, leading to increased levels of PD-L1 and changes in macrophage polarization, suggesting that combining olaparib with other therapies may enhance its antitumor effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. Moutafi, M., Koliou, GA., Papaxoinis, G., et al.[2023]

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. 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]

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Salvage Reconstructive Surgery During Nivolumab Therapy for a Patient With Hypopharyngeal Cancer. [2022]

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

Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. [2020]

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

Phase II Window Study of Olaparib Alone or with Cisplatin or Durvalumab in Operable Head and Neck Cancer. [2023]

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

Phase II Trial of Adjuvant Nivolumab Following Salvage Resection in Patients with Recurrent Squamous Cell Carcinoma of the Head and Neck. [2023]

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]

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

Neoadjuvant and Adjuvant Nivolumab and Lirilumab in Patients with Recurrent, Resectable Squamous Cell Carcinoma of the Head and Neck. [2023]

12. England pubmed.ncbi.nlm.nih.gov

Successful treatment with nivolumab in a patient with unresectable oral squamous cell carcinoma following ineffective chemoradiotherapy. [2023]