Immunotherapy for Meningioma

Overseen By David A Reardon, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Brainstem tumors, Active infection, 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: 6 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in this study are nivolumab and ipilimumab.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that you should not be on high-dose systemic corticosteroids or other investigational agents. It's best to discuss your current medications with the study team to see if they are allowed.

Is nivolumab (Opdivo) safe for use in humans?

Nivolumab, used in treating various conditions, has shown that 20% of patients experienced serious treatment-related side effects in a study for high-grade meningiomas. This suggests that while it can be effective, there are potential safety concerns that need to be considered. ^{1 2 3 4 5}

How is the drug Nivolumab unique in treating meningioma?

Nivolumab is unique for treating meningioma because it is an immunotherapy drug that blocks PD-1, a protein that helps cancer cells evade the immune system, potentially making it effective for tumors that are resistant to traditional treatments like surgery and radiation. ^{1 3 4 5 6}

What data supports the effectiveness of the drug Nivolumab for treating meningioma?

Research suggests that Nivolumab, a drug that helps the immune system fight cancer, has shown promise in shrinking meningiomas (a type of brain tumor) in some patients. Studies indicate that targeting PD-1, a protein that helps tumors evade the immune system, may be effective for treating aggressive meningiomas. ^{1 4 5 7 8}

Who Is on the Research Team?

David Reardon, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

Adults with recurrent meningioma, a type of brain tumor, who've tried radiation or other treatments without success can join. They must be able to follow the study plan and use birth control if needed. People with severe illnesses, recent surgeries, live vaccines taken recently, HIV/AIDS, certain cancers within 3 years, active infections needing IV treatment or known allergies to trial drugs cannot participate.

Inclusion Criteria

Agreement to follow instructions for contraception

I am able to care for myself but may not be able to do active work.

My meningioma is confirmed and has returned or is getting worse.

Exclusion Criteria

I have received CTLA-4 therapy before, as part of cohort 2.

I haven't taken drugs that weaken my immune system in the last 3 months.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants in Cohort 2 receive external beam radiation therapy (IMRT, 3D-CRT, or proton-beam)

3-4 weeks

Treatment

Cohort 1 receives nivolumab monotherapy; Cohort 2 receives nivolumab and ipilimumab combination therapy followed by nivolumab monotherapy

6 months

Every 2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• External Beam RT
• Nivolumab

Trial Overview The trial is testing different doses of Nivolumab alone or combined with Ipilimumab and/or external beam radiation therapy (RT) as potential treatments for progressive/recurrent meningioma. The goal is to see how well these immunotherapies work in controlling the disease.

How Is the Trial Designed?

Group I: Cohort 2: Nivolumab in Combination with Ipilimumab Experimental Treatment 4 Interventions

* External Beam RT (IMRT, 3D-CRT, or proton-beam radiation therapy) * Followed by 4 cycles of Nivolumab (3 mg/kg every 3 weeks) + Ipilimumab (1 mg/kg every 3 weeks) * Followed by Nivolumab monotherapy (480 mg every 4 weeks).

Group II: Cohort 1 (original cohort): Nivolumab Monotherapy Experimental Treatment 2 Interventions

Nivolumab monotherapy (240 mg every 2 weeks)

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?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

This case report presents the first evidence that nivolumab, an anti-PD-1 therapy, can significantly reduce the size of a refractory meningioma in a patient being treated for advanced lung cancer.

The findings suggest that PD-1 checkpoint inhibitors may be a promising treatment avenue for meningiomas, warranting further research into their efficacy in this type of brain tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of intracranial meningioma following treatment with nivolumab: Case report and review of the literature. Gelerstein, E., Berger, A., Jonas-Kimchi, T., et al.[2018]

In a phase 2 trial involving 25 patients with recurrent high-grade meningiomas, pembrolizumab (a PD-1 inhibitor) demonstrated promising efficacy, achieving a 6-month progression-free survival rate of 48% and a median progression-free survival of 7.6 months.

While 20% of patients experienced significant treatment-related adverse events (grade 3 or higher), the results indicate that pembrolizumab may be a viable treatment option for some patients with these aggressive tumors, warranting further investigation into the tumor microenvironment's role in treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. Brastianos, PK., Kim, AE., Giobbie-Hurder, A., et al.[2022]

Citations

1. Scotland pubmed.ncbi.nlm.nih.gov

Regression of intracranial meningioma following treatment with nivolumab: Case report and review of the literature. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results. [2022]

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

Efficient ADCC killing of meningioma by avelumab and a high-affinity natural killer cell line, haNK. [2020]

4. Germany pubmed.ncbi.nlm.nih.gov

Systemic and local immunosuppression in patients with high-grade meningiomas. [2021]

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

Immune checkpoint inhibitor therapy for recurrent meningiomas: a retrospective chart review. [2022]

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

Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Basis for Immunotherapy for Treatment of Meningiomas. [2023]

8. Scotland pubmed.ncbi.nlm.nih.gov

PD-L1 expression in meningiomas. [2018]