Nivolumab + Relatlimab/Ipilimumab for Head and Neck Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Dan P. Zandberg

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dan Zandberg

Disqualifiers: Metastasis, Autoimmune disease, Hepatitis, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The aim of this study is to potentiate adaptive immunity to enhance the anti-tumor activity of anti-PD1 antibody by the addition of anti-CTLA4 antibody or anti-LAG3 antibody (relatlimab) given in subjects with resectable locally advanced HNSCC prior to surgical resection.

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.

What data supports the effectiveness of the drug combination Nivolumab and Ipilimumab for head and neck cancer?

A case study showed that a patient with difficult-to-treat head and neck cancer responded well to the combination of Nivolumab and Ipilimumab. Additionally, this combination has been effective in treating other cancers, like melanoma, suggesting potential benefits for head and neck cancer. ^{1 2 3 4 5}

Is the combination of Nivolumab and Ipilimumab safe for treating head and neck cancer?

The combination of Nivolumab and Ipilimumab has been used successfully in treating head and neck cancer, with no unexpected immune-related toxicities reported in early clinical trials. However, Nivolumab can cause rare immune-related side effects, such as tracheobronchial chondritis (inflammation of the windpipe and bronchial tubes). ^{2 3 5 6 7}

What makes the drug combination of Nivolumab, Relatlimab, and Ipilimumab unique for head and neck cancer?

This drug combination is unique because it uses a mix of immune checkpoint inhibitors, which help the body's immune system attack cancer cells more effectively. Nivolumab and Ipilimumab have shown success in treating other cancers, and their combination is being explored for head and neck cancer, offering a new option for patients who have limited treatments available. ^{2 3 8 9 10}

Research Team

Dan P. Zandberg

Principal Investigator

UPMC Hillman Cancer Center

Eligibility Criteria

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.

Trial Timeline

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)

Treatment Details

Interventions

• Ipilimumab (Checkpoint Inhibitor)
• Nivolumab (Checkpoint Inhibitor)
• Relatlimab (Checkpoint Inhibitor)

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.

Participant Groups

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)

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

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

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]

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]

References

1. United States 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. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

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

3. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

4. England 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. [2020]

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

Neoadjuvant immunotherapy prior to surgery for mucosal head and neck squamous cell carcinoma: Systematic review. [2022]

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

Nivolumab-related tracheobronchial chondritis: Extremely rare manifestation of an immune-related adverse effect. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Safety evaluation of pembrolizumab for treating recurrent head and neck squamous cell carcinoma. [2022]

8. Greece pubmed.ncbi.nlm.nih.gov

Investigation of the Efficacy and Safety of Nivolumab in Recurrent and Metastatic Nasopharyngeal Carcinoma. [2021]

9. Japan 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. [2023]

10. England 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. [2023]