Nivolumab for Brain Tumors

Recruiting at 3 trial locations

Overseen By Fabio Iwamoto, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fabio Iwamoto, MD

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

Disqualifiers: Autoimmune disease, Hepatitis B/C, 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: 2

Duration: 2 years

20 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them 14 days before starting the study treatment, unless they are inhaled, topical, or low-dose for brain tumor swelling.

What data supports the effectiveness of the drug Nivolumab for brain tumors?

Nivolumab has shown effectiveness in improving survival in other cancers, such as advanced squamous non-small cell lung cancer, and has been studied for safety and efficacy in patients with recurrent glioblastoma, a type of brain tumor. ^{1 2 3 4 5}

Is Nivolumab safe for humans?

Nivolumab, also known as Opdivo, is generally safe for humans but can cause rare side effects like encephalitis (inflammation of the brain), which may occur in 1% to 3% of cases. This condition can be serious but is often treatable with steroids if recognized early. ^{6 7 8 9 10}

How is the drug Nivolumab unique for treating brain tumors?

Nivolumab is unique for treating brain tumors because it is an immune checkpoint inhibitor that can modify the tumor immune environment, potentially enhancing immune cell infiltration and diversity, even though large molecules like it typically struggle to penetrate the blood-brain barrier. ^{4 5 11 12 13}

What is the purpose of this trial?

The objective of this study is to determine response rates (partial and complete responses) to nivolumab of recurrent or progressive IDH mutant (grades 2, 3 or 4) gliomas with prior exposure to alkylating agents.

Research Team

Fabio Iwamoto, MD

Principal Investigator

Columbia University

Eligibility Criteria

This trial is for adults with recurrent or progressive brain tumors (IDH mutant gliomas grades 2, 3, or 4) who have previously been treated with alkylating agents. Participants must be able to perform daily activities at a reasonable level (KPS of 60+), have measurable disease on MRI, and provide tumor samples. They need normal organ function tests and must consent to study requirements.

Inclusion Criteria

Participants must agree to use at least 1 highly effective method of contraception

I have a tumor in my brain that is visible and measures at least 10mm x 10mm on an MRI.

I am a woman who can have children and have a negative pregnancy test.

Exclusion Criteria

I have previously used specific inhibitors or checkpoint inhibitors.

Participants with an active, known, or suspected autoimmune disease

I haven't had chemotherapy or experimental treatments in the last 4 weeks, nor radiotherapy in the last 12 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Nivolumab 240 mg every 2 weeks for 8 cycles, then 480 mg every 4 weeks for up to 2 years

2 years

Every 2 weeks for 8 cycles, then every 4 weeks

Follow-up

Participants are monitored for progression-free survival and overall survival

36 months

Treatment Details

Interventions

• Nivolumab

Trial Overview The trial is testing the effectiveness of Nivolumab in treating IDH mutant gliomas that are recurring or worsening despite prior treatment. The main goal is to see how many patients experience partial or complete shrinkage of their tumors after receiving this drug.

Participant Groups

Group I: Nivolumab Experimental Treatment 1 Intervention

Nivolumab 240 mg will be given every 2 weeks for 8 cycles. Beginning with Cycle 9, nivolumab 480 mg will be given every 4 weeks for a total therapy duration of 2 years, or until progressive disease, unacceptable toxicity, or withdrawal of consent. Nivolumab will be administered as a 30-minute infusion. A finite treatment duration with immune therapies in this participant population remains an area of ongoing research; therefore the treatment duration chosen was 2 years.

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?

Fabio Iwamoto, MD

Lead Sponsor

Trials

1

Recruited

20+

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, an anti-PD-1 immunotherapy, was associated with immune-related encephalitis in a 60-year-old woman with recurrent head and neck cancer, highlighting a potential serious side effect of this treatment.

Despite the occurrence of immune-related toxicities, including encephalitis and hypothyroidism, the patient achieved a complete radiologic response one year after stopping nivolumab, demonstrating the efficacy of immunotherapy in managing advanced cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoimmune-related encephalitis during treatment with nivolumab for advanced head and neck cancer: a case report. Guidi, A., Violati, M., Blasi, M., et al.[2022]

Nivolumab, an immune checkpoint inhibitor, significantly improved overall survival and progression-free survival compared to docetaxel in patients with advanced squamous non-small cell lung cancer (NSCLC) in the CheckMate 017 trial.

Nivolumab was better tolerated than docetaxel, with manageable adverse effects, making it a promising treatment option for patients who have already undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. Keating, GM.[2022]

Nivolumab plus ipilimumab significantly improved overall survival in patients with metastatic non-small cell lung cancer (NSCLC), including those with baseline brain metastases, compared to chemotherapy, with a hazard ratio of 0.63 for those with brain metastases and 0.76 for those without.

At 5 years, patients with baseline brain metastases treated with nivolumab plus ipilimumab had higher rates of systemic (12%) and intracranial (16%) progression-free survival compared to chemotherapy (0% and 6%, respectively), and fewer developed new brain lesions (4% vs. 20%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. Reck, M., Ciuleanu, TE., Lee, JS., et al.[2023]

In a study involving 40 newly diagnosed and 86 recurrent glioblastoma patients, PD-L1 blockade with durvalumab did not meet primary efficacy endpoints, indicating it was ineffective in improving outcomes compared to standard treatments.

Recurrent glioblastoma patients exhibited significantly lower levels of circulating immune cell subsets, and the use of dexamethasone was associated with a reduction in these immune cells, suggesting that immune suppression may hinder treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. Nayak, L., Standifer, N., Dietrich, J., et al.[2023]

Nivolumab, an immune checkpoint inhibitor approved for non-small cell lung cancer, can cause rare but serious side effects like immune-related encephalitis in 1% to 3% of patients, highlighting the need for awareness among healthcare providers.

In a case study of a 74-year-old male with stage 4 lung cancer, early recognition and treatment with intravenous steroids led to significant recovery from nivolumab-induced encephalitis, emphasizing the importance of prompt management to reduce risks of severe complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. Richard, K., Weslow, J., Porcella, SL., et al.[2018]

In a review of 3,763 patients with advanced melanoma treated with nivolumab and ipilimumab, 0.93% experienced serious neurologic immune-related adverse events (irAEs), including encephalitis, with a median onset time of 45 days.

Most neurologic irAEs resolved (75% of cases), but awareness and prompt management of these rare but serious events are crucial for oncologists and neurologists to prevent complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. Larkin, J., Chmielowski, B., Lao, CD., et al.[2018]

A case study of a 59-year-old woman with treatment-resistant laryngeal cancer revealed that nivolumab, an immunotherapy drug, can cause severe central nervous system (CNS) toxicities, specifically acute demyelinating encephalitis, which is rarely reported in the literature.

The patient's symptoms improved significantly after discontinuing nivolumab and receiving high-dose steroids and immunoglobulin therapy, suggesting that CNS toxicity from immune checkpoint inhibitors may be reversible with prompt treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. Zafar, Z., Vogler, C., Hudali, T., et al.[2020]

Nivolumab, a widely used chemotherapy drug for various cancers, has well-documented common side effects, but this study highlights the extremely rare occurrence of encephalitis as a side effect.

Reporting rare side effects like encephalitis is crucial as the field of cancer treatment evolves and more chemotherapeutic agents are introduced, ensuring better patient safety and awareness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. Chaucer, B., Stone, A., Demanes, A., et al.[2020]

Nivolumab combined with radiotherapy and temozolomide (NIVO+RT+TMZ) is tolerable for patients with newly diagnosed glioblastoma, with no new safety concerns identified; however, higher rates of grade 3/4 treatment-related adverse events were observed compared to Nivolumab with radiotherapy alone (NIVO+RT).

The study found that overall survival (OS) was similar for patients with unmethylated MGMT promoter whether they received NIVO+RT+TMZ or NIVO+RT, indicating that the addition of temozolomide may not significantly improve outcomes in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. Omuro, A., Reardon, DA., Sampson, JH., et al.[2023]

Nivolumab and ipilimumab show significant intracranial activity in patients with melanoma brain metastases, with response rates of 46% and 57% in two phase II studies, respectively.

Nivolumab can penetrate the cerebrospinal fluid (CSF), achieving concentrations that are effective for therapeutic action, challenging the belief that large molecules like monoclonal antibodies cannot affect the central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. van Bussel, MTJ., Beijnen, JH., Brandsma, D.[2020]

A phase II clinical trial involving 30 patients with glioblastoma tested the safety and immunological effects of the PD-1 inhibitor nivolumab, showing enhanced immune responses in the tumor microenvironment after treatment.

While the study did not demonstrate clear clinical benefits for most patients, two out of three patients who received nivolumab before and after primary surgery had prolonged survival, living 33 and 28 months post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. Schalper, KA., Rodriguez-Ruiz, ME., Diez-Valle, R., et al.[2019]

References

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

Autoimmune-related encephalitis during treatment with nivolumab for advanced head and neck cancer: a case report. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Nivolumab: a review in advanced squamous non-small cell lung cancer. [2022]

3. Japan pubmed.ncbi.nlm.nih.gov

Efficacy and safety of nivolumab in Japanese patients with first recurrence of glioblastoma: an open-label, non-comparative study. [2022]

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

Systemic and Intracranial Outcomes With First-Line Nivolumab Plus Ipilimumab in Patients With Metastatic NSCLC and Baseline Brain Metastases From CheckMate 227 Part 1. [2023]

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

Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. [2023]

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

A Case Report of Steroid Responsive Nivolumab-Induced Encephalitis. [2018]

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

Neurologic Serious Adverse Events Associated with Nivolumab Plus Ipilimumab or Nivolumab Alone in Advanced Melanoma, Including a Case Series of Encephalitis. [2018]

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

Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review. [2020]

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

Nivolumab-Induced Encephalitis in Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome. [2020]

10. England pubmed.ncbi.nlm.nih.gov

Nivolumab plus radiotherapy with or without temozolomide in newly diagnosed glioblastoma: Results from exploratory phase I cohorts of CheckMate 143. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Intracranial antitumor responses of nivolumab and ipilimumab: a pharmacodynamic and pharmacokinetic perspective, a scoping systematic review. [2020]

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

Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma. [2019]

13. Japan pubmed.ncbi.nlm.nih.gov

The Significant Antitumor Activity of Nivolumab in Lung Adenocarcinoma with Choriocarcinomatous Features. [2019]