Immunotherapy for Brain Cancer

Not currently recruiting at 6 trial locations

Overseen By Kathryn Partridge

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Immunosuppressants, Anti-angiogenics

Disqualifiers: Immunodeficiency, Active infection, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new immunotherapy treatment, MK-3475, for glioblastoma, an aggressive brain cancer. The researchers aim to determine if this treatment can effectively target and control cancer cells. Participants will be randomly assigned to receive the treatment either before and after surgery or only after surgery. Those diagnosed with glioblastoma or a similar brain cancer, who have experienced a recurrence after initial treatment, may be a good fit for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like high-dose corticosteroids or recent investigational agents may affect eligibility, so it's best to discuss your specific medications with the trial team.

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

Research has shown that pembrolizumab, also known as MK-3475, has been tested in people with glioblastoma, a type of brain cancer. In these studies, pembrolizumab was used alongside other treatments. The results indicated that the treatment was generally safe and manageable for patients. One study focused on patients with glioblastoma who received pembrolizumab with other therapies and found that the combination was manageable, with expected and manageable side effects.

Another study combined pembrolizumab with standard therapy and found it effective without causing unexpected problems. Patients experienced some side effects, but they were similar to those seen in other cancer treatments.

Overall, the research supports that pembrolizumab is safe for patients with glioblastoma. While side effects occur, they are usually not severe and can be managed by healthcare providers. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Unlike the standard treatments for brain cancer, which often involve surgery, radiation, and chemotherapy, MK-3475 (Pembrolizumab) acts as an immunotherapy, working with the body's immune system to fight cancer cells. Researchers are excited about Pembrolizumab because it targets the PD-1 pathway, a mechanism that tumors use to hide from the immune system. By blocking this pathway, MK-3475 can potentially enhance the immune response against cancer cells, offering hope for improved outcomes. Additionally, Pembrolizumab's administration both before and after surgery could provide a new strategy in managing brain cancer, potentially increasing its effectiveness compared to treatments applied solely after surgical intervention.

What evidence suggests that this treatment might be an effective treatment for Glioblastoma?

Research has shown that pembrolizumab (MK-3475) may help treat tumors with many mutations. In some studies, patients responded well to the treatment, and their disease progressed more slowly. For glioblastoma, early results indicated that patients lived a median of 12.9 months, with 62.5% surviving at least 12 months. In this trial, participants will be randomized into two groups: one group will receive pembrolizumab pre-surgery and continue post-surgery, while the other group will receive pembrolizumab only post-surgery. Although immunotherapy hasn't always worked for glioblastoma, combining pembrolizumab with other treatments like electric fields or MRI-guided laser ablation might enhance its effectiveness by boosting the immune system and improving access to the tumor. These findings suggest pembrolizumab could be a useful option for treating glioblastoma. ^{4 6 7 8 9}

Who Is on the Research Team?

Patrick Wen, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with Grade IV malignant glioma (glioblastoma or gliosarcoma) who have undergone initial treatment and are at their first or second relapse. Participants must be over 18, able to consent, have a performance status indicating they can carry out daily activities, and show tumor progression on scans. They should also have normal organ function as defined by the study's criteria.

Inclusion Criteria

Participants must have shown unequivocal evidence for tumor progression by MRI or CT scan.

My brain tumor is confirmed as a high-grade glioma (glioblastoma or gliosarcoma).

Table 1 Adequate Organ Function Laboratory Values

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Pre-surgery Treatment

Pembrolizumab (MK-3475) administered pre-surgery at a predetermined dosage

2 weeks

1 visit (in-person)

Post-surgery Treatment

Pembrolizumab (MK-3475) administered every 3 weeks post-surgery

6 months

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• MK-3475

Trial Overview The trial is testing Pembrolizumab (MK-3475), an immunotherapy drug, in patients with recurrent/progressive Glioblastoma that can be accessed surgically. It aims to understand how this drug affects early immune responses against the tumor.

How Is the Trial Designed?

Group I: Pre-surgery MK-3475 Experimental Treatment 1 Intervention

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK3475) pre-surgery at pre-determine dosage followed by Pembrolizumab at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Group II: No MK-3475 at Pre-Surgery Active Control 1 Intervention

-After a screening phase of 14 days, eligible subjects will be randomized into two groups. * Pembrolizumab (MK-3475) at pre-determine dosage every 3 weeks post surgery. * MK-3475 will be administered intravenously

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

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

Published Research Related to This Trial

MK-8389 was found to be generally safe and well tolerated in healthy young women over a 14-day period, although it caused transient changes in thyroid function tests that limited dose escalation above 40 mg.

While MK-8389 showed acceptable systemic exposure, it did not have a clinically meaningful effect on follicular development, although higher doses did increase inhibin B levels, indicating some early follicular activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral follicle-stimulating hormone agonist tested in healthy young women of reproductive age failed to demonstrate effect on follicular development but affected thyroid function. Gerrits, MG., Kramer, H., el Galta, R., et al.[2016]

Malignant brain tumors remain difficult to treat, with long-term survival only improving from 6 to 15 months over the last 80 years, despite advancements in surgery, chemotherapy, and radiotherapy.

Immunotherapy, particularly using immune modulators like CTLA-4 and PD-1/PD-L1, is being actively researched in ongoing phase I and III trials, showing promise in targeting glioma antigens, but challenges remain in achieving complete responses and understanding the lack of adverse brain inflammation in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The value of EGFRvIII as the target for glioma vaccines. Lowenstein, PR., Castro, MG.[2021]

Intravenous doses of MK-462 ranging from 5 to 90 micrograms per kg were found to be well tolerated in healthy males, with linear pharmacokinetics observed for doses up to 60 micrograms per kg.

Food intake prior to oral administration of MK-462 increased its overall exposure (AUC) by about 20% but did not significantly affect peak concentration (Cmax) or half-life (t1/2), indicating that MK-462 can be taken with or without food without major impacts on its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and food interaction of MK-462 in healthy males. Cheng, H., Polvino, WJ., Sciberras, D., et al.[2012]

The INTERCEPT H3 trial is investigating the safety and immunogenicity of the H3K27M-vac vaccine in combination with standard radiotherapy and the immune checkpoint inhibitor atezolizumab in 15 adult patients with newly diagnosed diffuse midline gliomas (DMG) carrying the H3K27M mutation.

Preliminary results from earlier studies suggest that the H3K27M-vac vaccine can induce specific immune responses that may help suppress tumor growth, making it a promising treatment strategy for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

INTERCEPT H3: a multicenter phase I peptide vaccine trial for the treatment of H3-mutated diffuse midline gliomas. Grassl, N., Sahm, K., Süße, H., et al.[2023]

MK-801 significantly reduces brain lesion volume and cerebral edema in rat models of acute brain injury, based on a systematic review of 52 studies involving 2530 samples.

The treatment with MK-801 also improves neurological function and spatial cognition, indicating its potential as a neuroprotective agent with a favorable safety profile for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MK-801 attenuates lesion expansion following acute brain injury in rats: a meta-analysis. Yi, NX., Zhou, LY., Wang, XY., et al.[2022]

The H3.3K27M-targeted peptide vaccine was well tolerated in patients with diffuse midline gliomas, with no severe treatment-related adverse events reported, indicating a favorable safety profile.

Patients who developed H3.3K27M-reactive CD8+ T cell responses had a significantly longer overall survival (median OS of 16.1 months) compared to those who did not respond, highlighting the potential efficacy of the vaccine in improving outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mass cytometry detects H3.3K27M-specific vaccine responses in diffuse midline glioma. Mueller, S., Taitt, JM., Villanueva-Meyer, JE., et al.[2022]

MK-571, a leukotriene D4 receptor antagonist, was well tolerated in both intravenous and oral forms, with no serious side effects reported, even at high doses up to 1500 mg.

The study showed that MK-571 is rapidly absorbed when taken orally, with peak plasma concentrations reached within 1-2 hours, and a modest accumulation of the drug in plasma over multiple doses, indicating its potential for effective long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma drug profiles and tolerability of MK-571 (L-660,711), a leukotriene D4 receptor antagonist, in man. Depré, M., Margolskee, DJ., Hsieh, JY., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11711056/

Pembrolizumab efficacy in a tumor mutation burden‐high ... The rapid disease progression, indicated by 80% Ki67 positivity, was markedly countered by the positive outcome of pembrolizumab treatment. This ...

2. nature.com nature.com/articles/s41423-024-01226-x

Immunotherapy for glioblastoma: current state, challenges ... Early data from this trial demonstrated that the mOS was 12.9 months, and the 12-month OS rate was 62.5% in 16 patients treated with the highest ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025001357

Efficacy and safety of adjuvant TTFields plus ... This study confirms that the use of TTFields in conjunction with pembrolizumab enhances immune recognition and anti-tumor immunity, significantly improving PFS ...

4. news.keckmedicine.org news.keckmedicine.org/could-electric-fields-supercharge-immune-attack-on-the-deadliest-form-of-brain-cancer/

USC study unlocks new potential treatment for glioblastoma Immunotherapy, while successful in many other cancer types, has also not proved effective for glioblastoma when used on its own. However, in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02311582

NCT02311582 | MK-3475 in Combination With MRI-guided ... MRI-guided laser ablation (MLA) has been noted to disrupt peritumoral the blood brain barrier (BBB), which may then lead to increased access of new tumor ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02311582

NCT02311582 | MK-3475 in Combination With MRI-guided ... The blood brain barrier (BBB) is a major obstacle to drug delivery in the treatment of malignant brain tumors including glioblastoma multiforme (GBM).

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40466642/

Efficacy and safety of adjuvant TTFields plus ... 31 newly diagnosed glioblastoma patients were enrolled post-chemoradiation to evaluate synergy between TTFields, pembrolizumab, and temozolomide.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03197506

Pembrolizumab and Standard Therapy in Treating Patients ... This phase II trial studies the side effects and how well pembrolizumab works in combination with standard therapy in treating patients with glioblastoma.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.2055

Safety and tolerability of olaparib, temozolomide ... The combination of olaparib, temozolomide, and pembrolizumab demonstrates a tolerable safety profile in patients with progressive glioblastoma.