Ipilimumab for Head and Neck Cancer

Overseen By Rom S. Leidner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Providence Health & Services

Must not be taking: Oral steroids

Disqualifiers: Autoimmune diseases, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 7-10 days

18 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, but you cannot participate if you need to take oral steroids at a dose of 20mg or more of prednisone daily. Inhaled steroids are allowed.

Is Ipilimumab generally safe for humans?

Ipilimumab has been shown to cause adverse events (side effects) in most patients, which are usually mild to moderate and related to the immune system. However, some people may experience severe and life-threatening side effects, so close monitoring and early treatment of these side effects are important. ^{1 2 3 4 5}

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

Ipilimumab is unique because it is an immunotherapy drug that works by blocking CTLA-4, a molecule that inhibits T-cell activation, thereby enhancing the body's immune response against cancer cells. Unlike traditional chemotherapy, which directly targets cancer cells, Ipilimumab boosts the immune system to fight the cancer, and it is being explored in combination with other immunotherapies like Nivolumab for potentially better outcomes in head and neck cancer. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is for patients with squamous cell carcinoma of the head and neck (SCCHN). This study will test the feasibility of the administration of intratumoral injections of ipilimumab prior to surgical resection, and the immune system response to treatment.

Research Team

R. Bryan Bell, MD, DDS

Principal Investigator

Providence Health & Services

Rom S Leidner, MD

Principal Investigator

Providence Health & Services

Eligibility Criteria

This trial is for adults with head and neck squamous cell carcinoma who are scheduled for surgery. They must be able to undergo a biopsy, handle the treatment, and sign consent. Men and women must agree to avoid pregnancy post-treatment. Excluded are those with certain infections, need high-dose steroids, have active autoimmune diseases or conditions that increase bowel perforation risk.

Inclusion Criteria

Patients must have blood test results within protocol-specified parameters

I agree not to try to father a child for 165 days after treatment ends.

I agree not to become pregnant for 105 days after treatment ends.

Exclusion Criteria

I have a history of serious digestive system issues.

I don't have conditions like bleeding, infections, colitis, or mental health issues that would make it unsafe for me to join the study.

I do not have an active autoimmune or infectious disease like HIV, HBV, or HCV.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 3mg intratumoral injection of ipilimumab during a biopsy procedure

7-10 days

1 visit (in-person)

Surgical Resection

Surgical resection of tumor and involved lymph nodes is performed

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ipilimumab

Trial Overview The study tests intratumoral injections of Ipilimumab in patients before they have surgery to remove their cancer. It aims to see if this method is doable and how the immune system responds.

Participant Groups

Group I: Intratumoral Ipilimumab Experimental Treatment 1 Intervention

Patients receive a 3mg intratumoral injection of ipilimumab during a biopsy procedure.

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?

Providence Health & Services

Lead Sponsor

Trials

131

Recruited

827,000+

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 a study of 373 patients from 11 phase I clinical trials, ipilimumab-related grade 3/4 adverse events were more common in patients who responded to treatment, indicating a potential link between therapeutic response and toxicity.

The likelihood of experiencing severe adverse events increased with the number of additional agents used alongside ipilimumab, while longer treatment duration was associated with more low-grade toxicities but not high-grade ones.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. Chauhan, A., Kabir, T., Wu, J., et al.[2023]

In a comparison of anti-PD-1 drugs for recurrent/metastatic nasopharyngeal carcinoma (RM-NPC), camrelizumab showed the highest objective response rate (34.1%) among second-line therapies, while first-line nivolumab achieved a 40% response rate, indicating its effectiveness in treating this cancer.

Nivolumab and pembrolizumab demonstrated the best safety profiles for managing adverse events, particularly for lower-grade side effects, while camrelizumab combined with chemotherapy resulted in a significantly higher response rate (90.9%) compared to chemotherapy alone (64.1%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials. Lv, JW., Li, JY., Luo, LN., et al.[2020]

Ipilimumab has shown a positive impact on overall survival in patients with stage IV melanoma, with long-term follow-up indicating its effectiveness compared to conventional treatments.

While 84.8% of patients experience drug-related adverse events, most are mild to moderate; however, severe reactions can occur, necessitating careful monitoring and management, especially when combined with other therapies like vemurafenib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Camacho, LH.[2022]

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]

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]

Ipilimumab (Yervoy®) is an approved monoclonal antibody for treating malignant melanoma by blocking the CTLA-4 protein, which enhances T-cell responses against tumor cells, showing its efficacy in cancer immunotherapy.

Currently, ipilimumab is also being tested in phase III trials for prostate cancer and phase II trials for non-small cell lung cancer, indicating its potential for broader applications in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. Cameron, F., Whiteside, G., Perry, C.[2021]

Ipilimumab is a monoclonal antibody that enhances T cell activation by blocking the CTLA-4 receptor, leading to improved antitumor responses and has been shown to increase overall survival in patients with advanced melanoma, a condition with a poor prognosis.

While ipilimumab has demonstrated significant efficacy, it can cause serious immune-related adverse effects that require prompt management, highlighting the importance of monitoring patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. Graziani, G., Tentori, L., Navarra, P.[2020]

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]

Ipilimumab, a monoclonal antibody used to enhance anti-tumor T-cell responses, can cause significant side effects, including ipilimumab-induced hypophysitis (IH), which affects hormone levels and requires hormone replacement therapy in most cases.

In a review of 10 patients with IH, early detection and management guidelines were developed, highlighting the importance of monitoring hormone levels and recognizing imaging abnormalities, which often resolve without high-dose glucocorticoid therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. Lam, T., Chan, MM., Sweeting, AN., et al.[2022]

References

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

Prognostic and predictive factors associated with ipilimumab-related adverse events: a retrospective analysis of 11 NCI-sponsored phase I clinical trials. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials. [2020]

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

CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. [2022]

4. 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]

5. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Ipilimumab: first global approval. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Ipilimumab: a novel immunostimulatory monoclonal antibody for the treatment of cancer. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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

9. Australia pubmed.ncbi.nlm.nih.gov

Ipilimumab-induced hypophysitis in melanoma patients: an Australian case series. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Rationale for combined blockade of PD-1 and CTLA-4 in advanced head and neck squamous cell cancer—review of current data. [2020]