Nivolumab + HuMax-IL8 for Head and Neck Cancer

(Spark2 Trial)

Overseen By Tanguy Seiwert, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Immunosuppressants, Corticosteroids, Antivirals, others

Disqualifiers: Autoimmune disease, Uncontrolled infection, 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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and feasibility of using two drugs, nivolumab (also known as Opdivo, an immunotherapy drug) and HuMax-IL8, for individuals with squamous cell carcinoma of the head and neck who plan to undergo surgery. The trial includes two groups, each receiving a different dose of the drug combination to evaluate their effectiveness together. Candidates for this trial may have head or neck cancer that might require surgery and are either HPV-negative or have a high smoking history. As a Phase 2 trial, the research focuses on measuring 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, if you are on medications like corticosteroids or other immunosuppressive drugs, you may need to adjust them as the trial excludes those on high doses. 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 has shown that nivolumab, approved by the FDA for treating several cancers such as melanoma and lung cancer, is generally well-tolerated. Common side effects include fatigue, skin rash, and nausea, while serious side effects occur less frequently.

Early results suggest that HuMax-IL8 (also known as BMS-986253) is safe for people. This treatment blocks a protein that aids tumor growth. Previous studies reported that most patients experienced mild side effects like fatigue and headaches.

This trial tests a combination of nivolumab and HuMax-IL8. While each drug has proven safe individually, the effects of their combined use are still under investigation. The trial's phase indicates reasonable evidence for safety, but the combination's effects remain under exploration. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Nivolumab combined with HuMax-IL8 for head and neck cancer because it targets the immune system differently compared to traditional treatments like chemotherapy and radiation. Nivolumab is an immune checkpoint inhibitor that blocks the PD-1 pathway, enhancing the immune system's ability to fight cancer cells. Meanwhile, HuMax-IL8 reduces inflammation and helps the immune system focus more effectively on tumors. This dual approach not only aims to improve treatment efficacy but also potentially reduces side effects associated with conventional therapies.

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

Research has shown that Nivolumab improves survival rates for patients with recurring or spreading head and neck cancer. This suggests it might also benefit those with squamous cell carcinoma of the head and neck (SCCHN). In this trial, participants will receive a combination of Nivolumab and another drug, BMS-986253 (also known as HuMax-IL8), which targets the IL-8 pathway, crucial for enhancing the body's defense against tumors. Early studies with this combination have shown promise in making the treatment more effective by slowing tumor growth. These findings suggest that this treatment could be a good option for managing SCCHN. ^{2 4 6 7 8}

Who Is on the Research Team?

Tanguy Seiwert, M.D.

Principal Investigator

Johns Hopkins University/Sidney Kimmel Cancer Center

Are You a Good Fit for This Trial?

Adults with head and neck squamous cell carcinoma, including oral cavity or larynx cancers, who are HPV-negative or high-risk HPV-positive smokers. Candidates must be eligible for surgery, have a life expectancy of over 6 months, normal organ function, and no history of certain autoimmune diseases or prior treatments with specific immunotherapies.

Inclusion Criteria

A team of cancer specialists has approved me for surgery to remove my cancer.

My cancer is in the head or neck area, possibly caused by HPV.

You are expected to live for at least 6 more months.

Exclusion Criteria

I have an autoimmune disease, but it's controlled or unlikely to flare without a trigger.

My liver function tests are normal, and I'm not on antiviral medication.

I am not pregnant or nursing.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive pre-operative nivolumab in combination with BMS-986253

4 weeks

Surgery

Participants undergo surgical resection of the tumor

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days

Long-term Follow-up

Participants are monitored for relapse-free survival and overall survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cabiralizumab
• HuMax-IL8
• Nivolumab

Trial Overview The trial is testing the safety and feasibility of combining Nivolumab (an immune checkpoint inhibitor) with BMS-986253 (anti-interleukin-8) before surgery in patients. The goal is to target myeloid cells that can suppress the immune system's response to cancer.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Nivolumab (240 mg) + HuMax/BMS-986253 (3600 mg) will be administered as an IV infusion.

Group II: Cohort 1 Experimental Treatment 2 Interventions

Nivolumab (240 mg) + HuMax/BMS-986253 (2400 mg) will be administered as an IV infusion.

Nivolumab is already approved in United States, European Union, Canada, Switzerland for the following indications:

Approved in United States as Opdivo for:

• Advanced or metastatic gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma
• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Hepatocellular carcinoma
• Esophageal squamous cell carcinoma

Approved in European Union as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Canada as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Approved in Switzerland as Opdivo for:

• Melanoma
• Non-small cell lung cancer
• Renal cell carcinoma
• Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Gastroesophageal junction cancer
• Esophageal adenocarcinoma

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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, 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 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 (CheckMate 141) involving 361 patients with recurrent/metastatic squamous cell carcinoma of the head and neck, nivolumab significantly improved overall survival compared to investigator's choice of chemotherapy, with 30-month survival rates of 11.2% for patients under 65 and 13.0% for those 65 and older.

Nivolumab demonstrated a favorable safety profile, with lower rates of treatment-related adverse events compared to traditional chemotherapy, making it a viable option for older patients who may have difficulty tolerating standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age. Saba, NF., Blumenschein, G., Guigay, J., et al.[2020]

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]

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]

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 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]

Nivolumab has been shown to significantly improve survival rates in patients with recurrent or metastatic platinum-resistant head and neck squamous cell carcinoma (HNSCC) compared to standard chemotherapy, highlighting its efficacy as an immunotherapy targeting the PD-1 receptor.

HNSCC tumors exhibit the highest levels of PD-L1 expression among various tumor types, with 6.2% showing genetic alterations in PD-L1, suggesting that these tumors may be particularly responsive to PD-1/PD-L1 targeted therapies and that further investigation into related co-targets is warranted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The genetic landscape of programmed death ligand-1 (PD-L1) alterations in head and neck cancer. Heineman, TE., Widman, A., Kuan, EC., et al.[2021]

In a pooled analysis of 782 patients with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck, nivolumab demonstrated a median overall survival of 8.71 months, indicating its effectiveness in a real-world setting.

The study found that factors such as better performance status, platinum sensitivity, and older age were linked to longer overall survival, supporting the survival benefits observed in the Phase-III CheckMate 141 trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of nivolumab treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck in the United States and Germany. Singh, P., McDonald, L., Waldenberger, D., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-3-squamous-cell-carcinoma-of-head-and-neck-3-2021-085dd

Nivolumab + HuMax-IL8 for Head and Neck Cancer Research shows that Nivolumab, a part of the treatment, has been effective in improving survival rates for patients with recurrent or metastatic head and neck ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/32/NCT03400332/Prot_SAP_000.pdf

A Phase 1/2 Study of BMS-986253 in Combination With ... Part 2: The study design was changed to a randomized, double-blind investigation of BMS-986253 plus nivolumab plus ipilimumab versus placebo ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7644160/

Significance of the IL-8 pathway for immunotherapy - PMC We will be waiting for the new data derived from the clinical trial (phase 1b/2 study) of the combination of BMS-986253 plus nivolumab in a biomarker-enriched ...

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04848116/

Clinical Trial: NCT04848116 The primary objective of this study is to assess safety and feasibility of pre-operative nivolumab in combination with either cabiralizumab, ...

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6729083/

Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 ... HuMax-IL8 (now known as BMS-986253) is a novel, fully human monoclonal antibody that inhibits interleukin-8 (IL-8), a chemokine that promotes tumor progression.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/62/NCT04050462/Prot_SAP_000.pdf

A PHASE II, RANDOMIZED, CONTROLLED ... Nivolumab is FDA approved for treatment of patients with melanoma, non-small cell and small cell lung cancer, renal cell carcinoma, Hodgkin ...

8. fightcolorectalcancer.org fightcolorectalcancer.org/zh/clinical-trial/nct03400332/

A Study of BMS-986253 in Combination With Nivolumab or ... Upon administration, HuMax-IL8 directly binds to IL-8, thereby inhibiting the binding of IL-8 to its receptors CXCR1 and CXCR2. This inhibits activation of IL-8 ...