Nivolumab + BMS986205 for Head and Neck Cancer

Recruiting at 1 trial location

Overseen By Adam Luginbuhl, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Thomas Jefferson University

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Autoimmune disease, HIV/AIDS, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 weeks

45 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroid therapy or immunosuppressive therapy, you may need to stop these at least 14 days before starting the trial.

What data supports the effectiveness of the drug Nivolumab + BMS986205 for head and neck cancer?

Nivolumab has shown a clear clinical benefit for patients with recurrent or metastatic head and neck cancer, improving survival and quality of life, especially in patients with certain biomarkers. Additionally, combining nivolumab with other drugs has been successful in treating similar cancers, suggesting potential effectiveness when combined with BMS986205. ^{1 2 3 4 5}

Is the combination of Nivolumab and BMS-986205 safe for treating head and neck cancer?

Nivolumab, used alone or with other treatments, has been studied for head and neck cancer and is generally considered safe, with common side effects like diarrhea and skin rash. Studies show no unexpected serious immune-related side effects when used in similar treatments. ^{2 6 7 8 9}

What makes the drug Nivolumab + BMS986205 unique for head and neck cancer?

Nivolumab (Opdivo) is unique because it is an immunotherapy drug that targets the PD-1 protein, helping the immune system attack cancer cells, and it is specifically approved for patients with head and neck cancer who have not responded to platinum-based treatments. The combination with BMS986205, although not directly mentioned in the research, suggests a novel approach potentially enhancing the immune response compared to using Nivolumab alone. ^{1 4 10 11 12}

What is the purpose of this trial?

This phase II trial studies how well nivolumab works, with or without BMS986205, in treating patients with stage II-IV squamous cell cancer of the head and neck. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. BMS986205 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nivolumab with BMS986205 may work better than nivolumab alone in treating patients with squamous cell cancer of the head and neck.

Research Team

Adam Luginbuhl, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Eligibility Criteria

This trial is for adults with stage II-IV squamous cell cancer of the head and neck, including oral cavity and larynx cancers. Candidates must be fit for surgery, have a good performance status (able to carry out daily activities), normal organ function, and not be pregnant or breastfeeding. Men must use contraception during treatment and for 7 months after. People with HIV/AIDS, active hepatitis B/C, severe autoimmune diseases requiring recent treatment, other current cancers (with some exceptions), or history of certain blood disorders are excluded.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I have stage 2 or higher head and neck cancer and am a candidate for surgery.

Absolute neutrophil count 1500/ul or more

Exclusion Criteria

You have experienced serotonin syndrome in the past.

I or my close family have a history of cytochrome b5 reductase deficiency.

I have had lung inflammation or pneumonitis treated with steroids before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive nivolumab with or without BMS986205 for up to 5 weeks, followed by surgery based on treatment response

5 weeks

Weekly visits for treatment administration

Surgery

Surgery is performed based on treatment response after 5 weeks for Arm I and 4 weeks for Arm II

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Periodic follow-up visits

Treatment Details

Interventions

• IDO1 Inhibitor BMS-986205
• Nivolumab

Trial Overview The study is testing the effectiveness of Nivolumab alone or combined with an enzyme inhibitor called BMS986205 in treating head and neck cancer. Nivolumab is an immunotherapy drug that helps the immune system attack cancer cells. BMS986205 aims to block enzymes that tumor cells need to grow. The combination may improve outcomes compared to using Nivolumab by itself.

Participant Groups

Group I: Arm I (BMS986205, nivolumab) Experimental Treatment 4 Interventions

Patients receive IDO1 inhibitor BMS-986205 PO QD. Beginning week 2, patients also receive nivolumab IV over 30 minutes on day 1. Treatment repeats for up to 5 weeks in the absence of disease progression or unacceptable toxicity. Patients showing a treatment response receive IDO1 inhibitor BMS-986205 PO QD for 4 additional weeks and receive nivolumab IV over 30 minutes on day 1, then undergo surgery at week 10. Those without a treatment response after 5 weeks undergo surgery within 7 days.

Group II: Arm II (nivolumab) Active Control 3 Interventions

Patients receive nivolumab IV over 30 minutes on day 1 in the absence of disease progression or unacceptable toxicity. Patients showing treatment response after 4 weeks receive nivolumab IV over 30 minutes on day 1, then undergo surgery at week 9. Those without a treatment response after 4 weeks undergo surgery within 7 days.

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?

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

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

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]

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]

Patients with advanced head and neck cancer who had no pre-existing comorbidities experienced significantly longer overall survival and progression-free survival when treated with immunotherapy, indicating that comorbidities negatively impact treatment outcomes.

Interestingly, while patients without comorbidities had better survival rates, they also faced a higher risk of immune-related adverse events (irAEs), suggesting a complex relationship between health status and treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy. Guller, M., Cooper, DJ., Alkhatib, H., et al.[2023]

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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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

3. Switzerland pubmed.ncbi.nlm.nih.gov

Unexpected Response to Nivolumab in a "Fast Progressor" Head and Neck Cancer Patient. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Immune gene expression in head and neck squamous cell carcinoma patients. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Nivolumab for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: A Retrospective Tertiary Centre's Real-World Experience. [2023]

6. England pubmed.ncbi.nlm.nih.gov

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

7. Australia pubmed.ncbi.nlm.nih.gov

Age-based efficacy and safety of nivolumab for recurrent or metastatic head and neck squamous cell carcinoma: A multicenter retrospective study. [2021]

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

Impact of comorbidities on outcomes in patients with advanced head and neck cancer undergoing immunotherapy. [2023]

9. Greece pubmed.ncbi.nlm.nih.gov

Real-world Data Study of the Efficacy and Toxicity of Nivolumab vs. Cetuximab and Predictors of Response to Nivolumab in Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck in a European Population. [2023]

10. Greece pubmed.ncbi.nlm.nih.gov

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

11. 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]

12. England 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. [2020]