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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with squamous cell carcinoma of the head and neck that has returned after initial treatment. It combines two immunotherapy drugs, Nivolumab (Opdivo) and Lirilumab, which aim to enhance the body's immune response against cancer. Participants will receive these drugs before undergoing salvage surgery. Those who have remained disease-free for more than 8 weeks after their initial treatment and are eligible for surgery might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that using nivolumab and lirilumab together yields promising safety results for treating head and neck cancer. In previous studies, researchers tested this drug combination on patients with advanced stages of the disease. The objective response rate (ORR), which measures tumor shrinkage, was 24% among 29 patients. This rate increased to 41% for patients with PD-L1 positive tumors.

Nivolumab has been used for other conditions, indicating some established safety. Common side effects include tiredness, skin rash, and itching. Lirilumab has also been generally well-tolerated in earlier studies, with mild side effects like fatigue and slight fever reported by some patients.

Overall, while these drugs can cause side effects, research suggests they are manageable for many patients. Importantly, earlier studies have tested these drugs together, providing some confidence in their combined safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nivolumab and Lirilumab for head and neck cancer because these drugs work together to supercharge the immune system. Unlike standard treatments like chemotherapy or radiation, which directly attack cancer cells, Nivolumab and Lirilumab target immune checkpoints, specifically PD-1 and KIR receptors, to invigorate the body's natural defenses against tumors. This approach not only enhances the immune response but also offers the potential for fewer side effects compared to traditional therapies. By harnessing the power of the immune system, these treatments could provide a promising alternative for patients who have limited options.

What evidence suggests that this trial's treatments could be effective for head and neck cancer?

In this trial, participants will receive a combination of nivolumab and lirilumab to treat head and neck cancer. Research has shown that using these drugs together may help treat this condition. Specifically, studies found that this combination benefited 24% of patients with advanced, hard-to-treat squamous cell carcinoma. The response improved to 41% in tumors that were inflamed and expressed the protein PD-L1, which can influence the immune system. Additionally, nivolumab alone tends to cause fewer severe side effects than standard treatments, potentially making it a safer option. These findings suggest that this combination could be effective, particularly for those with certain types of tumors. ^{2 3 6 7 8}

Who Is on the Research Team?

Glenn J. Hanna, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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

Ability to understand and the willingness to sign a written informed consent document

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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 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 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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9401515/

Neoadjuvant and Adjuvant Nivolumab and Lirilumab in ... Pathologic specimens obtained at the time of salvage surgery were reviewed by two experienced head and neck pathologists (KW and VYJ) blinded to outcome data.

2. nature.com nature.com/articles/s41598-025-19197-y

Low-dose nivolumab plus induction chemotherapy for ... ICI combinations as NACT have shown lower response rates: the IMCISION trial reported a response in 6.25% of 32 patients treated with nivolumab ...

3. innate-pharma.com innate-pharma.com/media/all-press-releases/interim-phase-1/2-data-show-encouraging-clinical-benefit-lirilumab-combination-opdivo-nivolumab-patients-advanced-platinum-refractory-squamous-cell-carcinoma-head-and-neck

Interim Phase 1/2 Data Show Encouraging Clinical Benefit for ... Objective response rate (ORR) was 24% in 29 evaluable patients and increased in inflamed (PD-L1 positive) tumors, with ORR of 41% in ...

4. news.bms.com news.bms.com/news/details/2016/Interim-Phase-12-Data-Show-Encouraging-Clinical-Benefit-for-Lirilumab-in-Combination-With-Opdivo-nivolumab-in-Patients-With-Advanced-Platinum-Refractory-Squamous-Cell-Carcinoma-of-the-Head-and-Neck/default.aspx

Interim Phase 1/2 Data Show Encouraging Clinical Benefit ... Objective response rate (ORR) was 24% in 29 evaluable patients and increased in inflamed (PD-L1 positive) tumors, with ORR of 41% in ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1602252

Nivolumab for Recurrent Squamous-Cell Carcinoma of the ... Nivolumab was associated with fewer toxic effects of grade 3 or 4 than standard therapy (13.1% vs. 35.1%) and with maintenance of quality of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8003537/

Safety and Treatment Outcomes of Nivolumab for the ... Efficacy and safety of nivolumab in 100 patients with recurrent or metastatic head and neck cancer—A retrospective multicentre study. Acta ...

7. opdivo.com opdivo.com/head-and-neck-cancer/clinical-trial-results

Clinical trial results for previously treated head and neck ... See how OPDIVO® (nivolumab) performed in clinical trials for certain adults with previously treated squamous cell head and neck cancer (SCCHN).

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT03341936/

Clinical Trial: NCT03341936 The purpose of this study is to evaluate effectiveness (how well the drug/s work) of nivolumab in combination with lirilumab in participants ...