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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two investigational immunotherapy drugs, nivolumab and ipilimumab, to determine their effectiveness in treating squamous cell carcinoma, a type of head and neck cancer, specifically in the oral cavity. Researchers aim to discover if these drugs, either individually or combined, can shrink tumors or halt their growth. Individuals diagnosed with squamous cell carcinoma of the oral cavity, with tumors larger than 2 cm or cancer spread to nearby lymph nodes, may be suitable for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in cancer treatment.

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.

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

Research has shown that using nivolumab and ipilimumab together can help treat certain cancers. In some studies, about 30% of patients experienced serious side effects with this combination, though these studies occurred in different contexts. It is important to note that the FDA has already approved these drugs for other uses, indicating a degree of safety.

Nivolumab alone is generally well-tolerated. One study found that only 15.1% of patients experienced immune-related side effects, and just 6.7% discontinued treatment due to these effects. This is encouraging, as it suggests most people did not encounter severe problems.

These studies indicate that while side effects can occur, many patients can manage the treatments without serious issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nivolumab and Ipilimumab for head and neck cancer because these treatments offer a novel approach compared to traditional chemotherapy and radiation. Unlike standard treatments that generally target cancer cells directly, Nivolumab and Ipilimumab are immunotherapies that work by boosting the body's own immune system to fight the cancer. Nivolumab blocks a protein called PD-1, which helps the immune system recognize and attack cancer cells, while Ipilimumab targets another protein called CTLA-4, enhancing the immune response even further. This dual-action approach could potentially lead to more effective and longer-lasting outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Squamous Cell Carcinoma?

Research has shown that using nivolumab and ipilimumab together can significantly reduce the risk of disease progression or death. One study found that patients taking both drugs had a 38% lower risk compared to those taking only nivolumab. This trial will include a treatment arm where participants receive both nivolumab and ipilimumab. This combination also extended patients' lives by an average of 15.1 months compared to other treatments. Another arm in this trial will involve participants receiving nivolumab alone, which has proven effective for previously treated head and neck cancer, causing fewer serious side effects and better maintaining quality of life than some standard treatments. These findings suggest that nivolumab and ipilimumab could effectively treat squamous cell carcinoma of the oral cavity. ^{2 3 6 7 8}

Who Is on the Research Team?

Jonathan Schoenfeld, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

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.

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

Lack of availability for follow up assessments

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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]

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, 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 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]

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]

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]

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]

Citations

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Real-World, Long-Term Outcomes of Nivolumab Therapy ... No real-world, long-term outcomes of immunotherapy with nivolumab for recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) have ...

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

Low-dose nivolumab plus induction chemotherapy for ... One-year progression-free survival and overall survival were 67% and 83%, respectively, with post-induction radical therapy (p < 0.001) and pCR/ ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18040

Real-world effectiveness and healthcare utilization of ... The median survival time for all-cause death was 6.0 months (95% CI: 5.0 – 7.3) and median time to nivolumab discontinuation was 2.6 months (95% ...

4. 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 ...

5. 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).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.17_suppl.LBA2

NIVOPOSTOP (GORTEC 2018-01): A phase III randomized ... Safety analysis up to 9 months after CRT was based on patients who received at least one administration of treatment. Patients experiencing ...

7. 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 ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33808781/

Safety and Treatment Outcomes of Nivolumab for the ... Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity.