Pembrolizumab for High-Grade Meningioma

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Immunodeficiency, Active TB, Autoimmune, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 9

Duration: Up to 26 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests pembrolizumab, an immunotherapy drug, to determine its effectiveness in treating high-grade meningioma, a type of brain tumor. The study targets individuals with meningiomas that are recurring or not fully removed by surgery. It suits those whose meningioma has grown despite surgery or radiation, or whose tumor has spread beyond the brain. Participants should not have received recent chemotherapy or other investigational treatments. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not take chemotherapy or other investigational agents within 14 days of starting the study treatment. You also cannot be on high-dose corticosteroids, but a stable dose of dexamethasone 2mg or less is allowed. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that pembrolizumab is likely to be safe for humans?

Research has shown that pembrolizumab is generally safe and well-tolerated in people. In a study involving patients with recurring high-grade meningiomas, pembrolizumab demonstrated promising safety results. Some participants experienced side effects, with about 16.7% encountering more serious side effects, known as grade 3 toxicity. Most side effects were less severe.

Another study combined pembrolizumab with a precise type of radiation treatment and suggested that this combination was safe and had positive effects. Although pembrolizumab has not significantly improved certain outcomes for all patients, the safety data remains strong.

The FDA's approval of pembrolizumab for other conditions adds confidence in its safety. However, like any treatment, risks exist, and potential participants should discuss these with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pembrolizumab is unique because it leverages the power of immunotherapy to treat high-grade meningioma, which is not commonly targeted by current treatments. Unlike traditional methods that often rely on surgery and radiation, Pembrolizumab acts by blocking the PD-1 pathway. This mechanism enables the immune system to better recognize and attack cancer cells. Researchers are excited about Pembrolizumab because it offers a novel approach that could potentially enhance treatment outcomes for patients with this challenging brain tumor.

What evidence suggests that pembrolizumab might be an effective treatment for high-grade meningioma?

Research shows that pembrolizumab, a type of immunotherapy, is being tested in this trial for high-grade meningioma, a kind of brain tumor. Previous studies have produced mixed results regarding its effectiveness. In some cases, pembrolizumab did not significantly extend the time during which the cancer remains stable. However, the drug has shown promise in treating other types of cancer, suggesting potential benefits for some patients. Although some patients experienced serious side effects, these findings indicate that pembrolizumab could offer hope for treating high-grade meningioma, especially when other treatments have failed. ^{1 2 3 6 7}

Who Is on the Research Team?

Priscilla K. Brastianos

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with recurrent or residual high-grade meningioma. Candidates can have had previous treatments but must show measurable disease progression post-radiation, if applicable. They should be in good physical condition (ECOG Performance Status < 2), not pregnant or nursing, and on a stable low dose of dexamethasone. People with brainstem lesions, active infections, certain psychiatric conditions, recent immunosuppressive treatments, known hypersensitivity to pembrolizumab or its components are excluded.

Inclusion Criteria

I have received treatment before.

My meningioma has grown after I completed radiation therapy.

I can do most of my daily activities without help.

Exclusion Criteria

I have not taken drugs that weaken my immune system in the last 3 months.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Participants who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pembrolizumab every 3 weeks through IV infusion

Up to 26 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 35 months

Every 6 weeks (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab

Trial Overview The study tests Pembrolizumab's effectiveness for treating high-grade meningioma that has recurred after treatment or remains after surgery. Participants will receive this immunotherapy drug to see how it affects their cancer compared to the standard care they would otherwise receive.

How Is the Trial Designed?

Group I: Pembrolizumab Experimental Treatment 1 Intervention

* Pembrolizumab will be administered every 3 weeks * Pembrolizumab will be administered through IV infusion

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Citations

1. nature.com nature.com/articles/s41467-022-29052-7

Phase 2 study of pembrolizumab in patients with recurrent ... Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35289329/

Phase 2 study of pembrolizumab in patients with recurrent and ... Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03279692

NCT03279692 | Phase II Trial of Pembrolizumab in ... This research study is studying a drug as a possible treatment for High Grade Meningioma. The drug involved in this study is an immunotherapy drug called ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11487343/

A phase II, open-label, single-arm trial of pembrolizumab for ... Three patients (16.7%) developed grade 3 toxicity. Conclusions. Our results showed that pembrolizumab failed to improve PFS-6 in patients with ...

5. onclive.com onclive.com/view/improved-understanding-of-genomics-drives-excitement-in-high-grade-meningiomas

Improved Understanding of Genomics Drives Excitement in ... Twenty percent of patients experienced at least 1 grade 3 or higher AE. “These results do suggest that pembrolizumab does exert promising ...

6. academic.oup.com academic.oup.com/neuro-oncology/article/26/Supplement_8/viii92/7890396

CTIM-31. PRELIMINARY RESULTS OF A PHASE II STUDY ... These preliminary data suggest that the combination of stereotactic radiosurgery and pembrolizumab is safe, well tolerated and may be beneficial ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38901486/

Immune Checkpoint Inhibition for High Grade Meningiomas Results: Four studies were included comprising 59 patients; 74.6% had World Health Organization grade II meningiomas and 25.4% had grade III ...