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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two immunotherapy drugs, nivolumab (Opdivo) and ipilimumab, to determine their effectiveness in treating recurrent meningioma. Meningioma is a type of brain tumor, and this trial targets individuals whose tumors have grown or returned after previous treatments. The trial consists of two parts: one tests nivolumab alone, while the other tests a combination of nivolumab and ipilimumab with radiation therapy. Suitable candidates have meningiomas that have returned or grown despite prior surgery or radiation. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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

Research shows that nivolumab, when used alone, is generally well-tolerated by patients with meningiomas, a type of brain tumor. Studies found that patients experienced few severe side effects with nivolumab alone.

For those receiving both nivolumab and ipilimumab, the combination is also well-tolerated, but reports of serious side effects are more frequent compared to nivolumab alone. Specifically, some patients experienced serious side effects, though these were less common.

Overall, studies have shown that both treatments have a manageable safety profile. While side effects can occur, they are often not severe enough to stop the treatment. Prospective trial participants should note that these findings suggest the treatments are relatively safe, though side effects may still occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling meningioma. Unlike traditional treatments such as surgery and radiation therapy, Nivolumab, an immunotherapy drug, leverages the body's immune system to fight cancer cells. This is especially promising since Nivolumab targets the PD-1 pathway, potentially enhancing the immune response against tumor cells. Furthermore, the combination therapy with Ipilimumab adds another layer of immune activation, which might improve outcomes compared to Nivolumab alone. These innovative mechanisms could lead to better treatment responses and improved survival rates for patients with this type of brain tumor.

What evidence suggests that this trial's treatments could be effective for recurrent meningioma?

Research has shown that using nivolumab alone, tested in one arm of this trial, has not significantly extended the time patients with recurring meningioma live without disease progression. However, another arm of this trial tests a combination of nivolumab with ipilimumab and radiation therapy, which may be more effective for treating aggressive meningiomas. Early studies suggest that most patients tolerate this combination well. While nivolumab is already used for other types of cancer, its effectiveness for meningioma remains under investigation. This combination therapy offers hope for those with challenging cases. ^{1 2 4 5 6}

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

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2084

Phase 2 study of nivolumab for patients with meningiomas ... A single-arm, open-label, phase 2 study was conducted to evaluate the efficacy and safety of nivolumab for meningiomas refractory to surgery and radiotherapy.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8730772/

Activity of PD-1 blockade with nivolumab among patients with ... In conclusion, PD-1 blockade with nivolumab administered as monotherapy failed to increase PFS-6 in this clinical trial for unselected patients with recurrent ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03604978

NCT03604978 | Nivolumab and Multi-fraction Stereotactic ... Giving nivolumab and multi-fraction stereotactic radiosurgery with or without ipilimumab may work better in treating patients with grade II-III meningioma.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S030384672030281X

Rapid development of an atypical meningioma during ... Nivolumab treatment for mccRCC has proven to be highly effective. It is the first approved immunotherapy for advanced RCC that shows a significant survival ...

5. dana-farber.org dana-farber.org/clinical-trials/15-490

An Open-Label Phase II Study of Nivolumab or ... This research study is studying targeted immunotherapies as a possible treatment for recurrent meningioma. The names of the study interventions involved in ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02648997

Study Details | NCT02648997 | An Open-Label Phase II ... This research is a Phase II clinical trial, which means it will test the safety and effectiveness of nivolumab alone (Cohort 1) or in combination with ...