Nivolumab + Relatlimab/Ipilimumab for Head and Neck Cancer

Overseen By Rosemarie Angelo, RN, BSN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dan Zandberg

Disqualifiers: Metastasis, Autoimmune disease, Hepatitis, 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: 4

Duration: 4 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies new treatment combinations for head and neck cancer, aiming to enhance the body's immune response by adding drugs like ipilimumab or relatlimab to nivolumab. The trial includes two groups: one receives nivolumab with relatlimab, and the other receives nivolumab with ipilimumab. Individuals with squamous cell carcinoma in specific head and neck areas who have not undergone prior radiation or chemotherapy might be suitable candidates. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have an active autoimmune disease that requires treatment, you may not be eligible to participate.

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

Research has shown that the combination of nivolumab and relatlimab has side effects similar to those known for each drug individually. This combination generally causes fewer adverse effects than the nivolumab and ipilimumab combination, which reassures patients concerned about side effects. However, specific information on side effects for the nivolumab-relatlimab combination in head and neck cancer patients is not available in current sources.

For the nivolumab and ipilimumab combination, studies have indicated that serious side effects occurred in about 48% of patients, with some being very severe and a small number fatal. Despite this, the treatment significantly improves survival in some cancers, suggesting a balance between benefits and risks.

As the trial is in a middle stage, the treatments might be well-tolerated, but potential risks remain. Patients should always consult a healthcare professional to understand what these findings mean for their personal situation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they combine immunotherapy drugs that target different aspects of the immune response to fight head and neck cancer. Nivolumab and Relatlimab work together to block proteins that usually stop the immune system from attacking cancer cells, while Ipilimumab enhances the body's immune activity. This dual or triple approach aims to boost the immune system's ability to recognize and destroy cancer cells more effectively than standard treatments, which often rely on surgery, radiation, or conventional chemotherapy. These combinations have the potential to offer a more targeted and potent response, potentially leading to better outcomes for patients with this challenging cancer.

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

In this trial, participants will receive either the combination of nivolumab and relatlimab or the combination of nivolumab and ipilimumab. Research has shown that using nivolumab and relatlimab together can help the immune system fight head and neck cancer more effectively. Early results suggest that this combination may improve survival rates more than using just one of these drugs. In other studies, about half of the patients benefited from this treatment.

For the combination of nivolumab and ipilimumab, studies have found it can significantly lower the risk of cancer progression or death compared to using nivolumab alone. This combination has also been linked to longer survival in patients. These findings suggest that these treatments could be effective for head and neck cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Dan P. Zandberg

Principal Investigator

UPMC Hillman Cancer Center

Are You a Good Fit for This Trial?

Adults with certain types of head and neck cancers that can be surgically removed are eligible. They must have tumors accessible for biopsy, no distant metastasis, a good performance status, and agree to use contraception. Excluded are those with hepatitis B or C, recent heart issues, previous cancer treatments within 5 years, severe reactions to monoclonal antibodies or active autoimmune diseases.

Inclusion Criteria

I have a specific type of throat cancer that has not been treated and meets certain size and spread criteria.

I agree to use birth control during and after the study, and I won't donate sperm.

Have signed written informed consent

Exclusion Criteria

I have been treated with LAG-3 targeted agents before.

I do not have a second primary tumor at the time of my emergency use authorization.

You have a mental illness or other problems that make it difficult for you to follow the study requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nivolumab alone or in combination with Relatlimab or Ipilimumab. Treatment includes IV administration on Day 1 and potentially Day 28 if surgery is postponed.

4 weeks

3 visits (in-person)

Surgery

Participants undergo surgical resection 4 weeks after treatment initiation.

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of peripheral blood lymphocytes and adverse events.

6 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Ipilimumab
• Nivolumab
• Relatlimab

Trial Overview

The trial is testing the safety and effectiveness of Nivolumab alone or combined with Relatlimab or Ipilimumab in treating head and neck cancer before surgery. The goal is to boost the body's immune response against tumor cells by using these drugs.

How Is the Trial Designed?

Group I: Nivolumab + Relatlimab Experimental Treatment 2 Interventions

Nivolumab 480mg IV + Relatlimab 480mg IV D1 - optional Nivolumab 480 mg IV + Relatlimab 480mg IV D28 (D28 at clinician discretion i.e. surgery postponed)

Group II: Nivolumab + Ipilimumab Experimental Treatment 2 Interventions

Nivolumab 3 mg/kg IV + Ipilimumab 1 mg/kg D1 then Nivolumab 3 mg /kg D14 and then optional Nivolumab 3 mg/kg D28 (D28 at clinician discretion i.e., surgery postponed)

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?

Dan Zandberg

Lead Sponsor

Trials

7

Recruited

330+

Robert Ferris

Lead Sponsor

Trials

7

Recruited

240+

Robert L. Ferris, MD, PhD

Lead Sponsor

Trials

2

Recruited

120+

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 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]

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 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]

Pembrolizumab, a PD-1 inhibitor, has shown significant overall response rates and survival benefits in patients with recurrent or metastatic head and neck squamous cell carcinoma compared to chemotherapy alone, particularly in populations with high PD-L1 expression (CPS ≥ 20 and CPS ≥ 1).

The safety profile of pembrolizumab is comparable to other PD-1/PD-L1 inhibitors, with common side effects including diarrhea and hypothyroidism, but it has a favorable toxicity profile compared to the EXTREME chemotherapy regimen, highlighting the importance of PD-L1 scoring for patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. Desilets, A., Soulières, D.[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 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]

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 a study of 41 patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab, those with lung metastasis had a significantly better prognosis compared to those with liver metastasis, indicating that the site of metastasis influences treatment outcomes.

Patients with lung metastasis were more likely to continue nivolumab treatment or receive subsequent chemotherapy (70% vs. 25% for liver metastasis), highlighting the importance of metastasis location in managing treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Site of distant metastasis affects the prognosis with recurrent/metastatic head and neck squamous cell carcinoma patients treated with Nivolumab. Hoshi, Y., Shirakura, S., Yamada, M., et al.[2023]

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 involving 400 patients with platinum-resistant recurrent or metastatic head and neck squamous cell carcinoma, higher tumor mutational burden (TMB) was associated with significantly improved overall survival when treated with the immune checkpoint inhibitor durvalumab, especially when combined with tremelimumab.

Blood plasma TMB (bTMB) levels of 16 mutations/megabase or higher were predictive of better survival outcomes compared to chemotherapy, indicating that bTMB can serve as a valuable biomarker for guiding treatment decisions in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Mutational Burden as a Predictor of Survival with Durvalumab and/or Tremelimumab Treatment in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Wildsmith, S., Li, W., Wu, S., et al.[2023]

Citations

1.

opdivohcp.com

opdivohcp.com/efficacy/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Efficacy ...

In patients receiving OPDIVO 3 mg/kg with YERVOY 1 mg/kg every 3 weeks, immune-mediated hepatitis occurred in 7% (48/666) of patients, including Grade 4 (1.2%), ...

2.

news.bms.com

news.bms.com/news/details/2025/Bristol-Myers-Squibb-Presents-Results-from-CheckMate--8HW-Analysis-Evaluating-Opdivo-nivolumab-plus-Yervoy-ipilimumab-Compared-to-Opdivo-Monotherapy/default.aspx

8HW Analysis Evaluating Opdivo® (nivolumab) plus ...

Patients experienced a 38% reduction in the risk of disease progression or death when treated with Opdivo plus Yervoy versus Opdivo monotherapy across all ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7352976/

Combination of Ipilimumab and Nivolumab in Cancers

Their results showed that OS was increased by 15.1 months in patients who received ipilimumab as compared to 7.8 months in other patients [60]. Their findings ...

4.

drugs.com

drugs.com/medical-answers/how-effective-opdivo-yervoy-when-taken-together-3577723/

How effective are Opdivo and Yervoy when taken together?

Among patients who remained progression-free at 3 years, an remarkable 96% achieved 10-year melanoma-specific survival with the Opdivo plus ...

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.

opdivohcp.com

opdivohcp.com/safety/nsclc/opdivo-yervoy

OPDIVO® (nivolumab) + YERVOY® (ipilimumab) Safety ...

Fatal adverse reactions occurred in 1% of patients; these included events of pneumonitis (0.6%). In Checkmate 901, serious adverse reactions occurred in 48% of ...

7.

ono-pharma.com

ono-pharma.com/sites/default/files/en/news/press/sm_cn170405_3.pdf

Opdivo (nivolumab) in Combination with Yervoy ( ...

“It is encouraging to see such positive data from this trial, which further supports the scientific rationale to combine Immuno-Oncology agents ...

8.

cancernetwork.com

cancernetwork.com/view/nivolumab-ipilimumab-yielded-superior-efficacy-and-safety-data-in-uhcc

Nivolumab/Ipilimumab Yielded Superior Efficacy and ...

For overall survival (OS), the combination of nivolumab plus ipilimumab showed a significant improvement in median OS compared with lenvatinib ( ...