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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called ipilimumab (also known as Yervoy) for individuals with squamous cell carcinoma of the head and neck. The researchers aim to determine the safety of injecting ipilimumab directly into the tumor before surgery and its effects on the immune system. Individuals planning to undergo surgery for this cancer and who can safely receive a tumor injection might be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive it.

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 there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ipilimumab has been tested with other treatments like nivolumab to assess its safety and effectiveness. In these studies, patients have experienced mixed results regarding safety. Some reported side effects such as tiredness, skin rash, or diarrhea, which are common with many cancer treatments. However, most patients tolerated the treatment well.

The trial available for participation is in its early stages (Phase 1), focusing primarily on assessing the treatment's safety for people. Ipilimumab is already approved for other uses, indicating that its safety is somewhat known. However, since this trial involves injecting it directly into tumors, different side effects specific to this method might occur.

Prospective participants should discuss any concerns with the trial team, who can provide detailed information about what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ipilimumab is unique because it targets the immune system in a way that is different from most standard treatments for head and neck cancer, which often rely on chemotherapy, radiation, or surgery. Unlike these conventional methods, ipilimumab is a type of immunotherapy that works by enhancing the body's natural immune response to fight cancer cells. Researchers are particularly excited about the intratumoral delivery of ipilimumab, meaning it's injected directly into the tumor, which potentially increases its effectiveness at the site of the cancer while minimizing systemic side effects. This targeted approach could offer a new avenue for treatment with the hope of better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that ipilimumab might be an effective treatment for head and neck cancer?

Research has shown that ipilimumab, administered as an intratumoral injection in this trial, is under study for its potential to help the immune system combat head and neck cancer. In one study, three out of fifteen patients maintained stable disease after 12 weeks, indicating a disease control rate of 20%. However, another study found that most patients experienced cancer progression within a few months, though one patient had delayed progression for over two years. These findings suggest that while ipilimumab may benefit some patients, its effectiveness can vary. The treatment aims to harness the body's immune response to directly target cancer cells. ^{6 7 8 9 10}

Who Is on the Research Team?

R. Bryan Bell, MD, DDS

Principal Investigator

Providence Health & Services

Rom S Leidner, MD

Principal Investigator

Providence Health & Services

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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]

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]

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]

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 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02812524?tab=history&a=2

Record History | ver. 2: 2017-06-13 | NCT02812524 This study will test the feasibility of the administration of intratumoral injections of ipilimumab prior to surgical resection, and the immune system response ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11029278/

Combined treatment with ipilimumab and intratumoral ... Three patients had stable disease 12 weeks after starting treatment, yielding a disease control rate of 20%. Tolerability of this combination ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S246829422200140X

Immunotherapy in head and neck squamous cell carcinoma This regimen has a median survival of 10.1 months, and almost no effective treatment is available in the recurrent setting as a second line [24]. KEYNOTE-048 ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1479483/full

Injecting hope: the potential of intratumoral immunotherapy ... Of the seven evaluable patients, five experienced progression at 4 months, one at 8 months, and one at 31 months after treatment. Progression in all patients ...

5. nature.com nature.com/articles/s41467-021-26472-9

Neoadjuvant immunotherapy with nivolumab and ... Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.02349

First-Line Nivolumab Plus Ipilimumab in Recurrent ... Here, the median OS was 17.6 months for immunotherapy combination (N = 185) compared with 14.6 months on the control arm (N = 178), yet with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10115555/

Nivolumab Plus Ipilimumab Versus EXTREME Regimen as ... Among patients with CPS ≥ 20, the median progression-free survival was 5.4 months (nivolumab plus ipilimumab) versus 7.0 months (EXTREME), ...

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2803086

The Phase 2 CheckMate 714 Randomized Clinical Trial Median OS was 10.0 months (95% CI, 6.5–11.4 months) for nivolumab plus ipilimumab vs 9.6 months (95% CI, 7.1–14.3 months) for nivolumab (HR, ...

9. news.bms.com news.bms.com/news/details/2024/Bristol-Myers-Squibb-Presents-Landmark-10-Year-Follow-Up-Data-from-CheckMate--067-Which-Showed-Continued-Durable-Long-Term-Survival-Benefit-with-Opdivo-plus-Yervoy-in-Advanced-Melanoma/default.aspx

067 Which Showed Continued Durable Long-Term ... With a minimum follow up of 10 years, median overall survival (OS) was 71.9 months with Opdivo plus Yervoy (95% CI: 38.2-114.4) - the longest ...

10. 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 ( ...