Nivolumab + BMS986205 for Head and Neck Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nivolumab (Opdivo), alone or with BMS986205 (an IDO1 inhibitor), can enhance the immune system's ability to combat head and neck cancer, specifically squamous cell cancer, which can spread and grow aggressively. The aim is to determine if the combination treatment is more effective than nivolumab alone. Individuals diagnosed with stage II-IV squamous cell cancer of the mouth, throat, or sinuses, who are candidates for surgery, might be suitable participants. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants an opportunity to contribute to significant advancements in cancer treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that nivolumab is generally well-tolerated by patients with head and neck cancer. In studies, only 15.1% of patients experienced immune-related side effects, and just 6.7% discontinued treatment due to these issues. Nivolumab also caused fewer serious side effects compared to standard treatments.

Another study found that BMS986205 effectively reduces certain enzyme levels linked to cancer without causing severe side effects. Patients taking BMS986205 with nivolumab reported positive safety outcomes.

Thus far, the combination of nivolumab and BMS986205 appears safe and manageable for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for head and neck cancer because they introduce innovative approaches to tackling the disease. Nivolumab is an immunotherapy that activates the immune system to target and destroy cancer cells, differing from traditional chemotherapy that directly kills cells, often harming healthy ones too. The addition of BMS-986205, an IDO1 inhibitor, is particularly exciting because it works by blocking a pathway that cancer cells use to hide from the immune system, enhancing the effects of nivolumab. This combination has the potential to improve the body's natural ability to fight cancer more effectively than current standard treatments.

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

Research has shown that using nivolumab with BMS986205, which participants in this trial may receive, may help treat head and neck cancer. In a study, patients who received both treatments responded better than those who only received nivolumab, another treatment option in this trial. This combination appears to help the immune system fight cancer cells and slow tumor growth. Early results suggest that tumors with higher levels of a certain enzyme, called IDO, responded especially well to this treatment. Most patients tolerate this combination well, making it a promising option. ^{1 3 4 6 7}

Who Is on the Research Team?

Adam Luginbuhl, MD

Principal Investigator

Sidney Kimmel Cancer Center at Thomas Jefferson University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 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 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]

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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.6070

Neoadjuvant nivolumab with or without IDO inhibitor in ... Conclusions: In previously untreated HNSCC, nivolumab +/- IDO inhibitor demonstrated a significantly greater pTE after a second dose in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03854032

Nivolumab and BMS986205 in Treating Patients With ... Giving nivolumab with BMS986205 may work better than nivolumab alone in treating patients with squamous cell cancer of the head and neck. Detailed Description.

3. asco.org asco.org/abstracts-presentations/ABSTRACT316209

Window-of-opportunity trial of nivolumab with or without the ... We designed a window-of-opportunity trial to test whether the IDO inhibitor BMS-986305 improves treatment responses and T cell function in SCCHN patients ...

4. news.bms.com news.bms.com/news/details/2017/Bristol-Myers-Squibb-to-Present-Data-That-Advances-Understanding-of-Effects-of-Immuno-Oncology-Therapies-on-Cancer-Biology-and-Patient-Outcomes-at-AACR-2017/default.aspx

Corporate news details First report of data evaluating investigational selective IDO1 inhibitor alone and in combination with Opdivo Initial presentation of overall survival data ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11973698

Response-Adaptive Surgical Timing in neoadjuvant ... Nivolumab + IDO inhibitor BMS986205 combination is well tolerated and tumors with increased IDO RNA expression at baseline had a significantly greater ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12187009/

Indoleamine 2,3-dioxygenase (IDO) inhibitors and cancer ... BMS-986205 (Linrodostat), another IDO1 inhibitor, was the first agent to demonstrate potent reduction of plasma kynurenine level in a clinical trial; a ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.TPS6595

Window-of-opportunity trial of nivolumab with or without the ... We designed a window-of-opportunity trial to test whether the IDO inhibitor BMS-986305 improves treatment responses and T cell function in SCCHN patients ...